Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs.Herein,chitosan conjugates(SPCS)installed with sialic acid(SA)and phenylbor...Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs.Herein,chitosan conjugates(SPCS)installed with sialic acid(SA)and phenylboronic acid(PBA)were synthesized,of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA.The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges.The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract.After reaching the lesions,the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release,while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside.The drugmicelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation.The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable,safe and flexible anti-infectious drug delivery systems.展开更多
Superconducting transition temperature(Tc),as a crucial parameter,exploring its relationship with various macroscopic and microscopic factors helps to understand the mechanism of high-temperature superconductivity fro...Superconducting transition temperature(Tc),as a crucial parameter,exploring its relationship with various macroscopic and microscopic factors helps to understand the mechanism of high-temperature superconductivity from multiple perspectives,aiding in a multidimensional comprehension of high-temperature superconductivity mechanisms.Drawing inspiration from the block-layer structure models of cuprate superconductors,we computationally investigated the interlayer interaction energies in the 12442-type iron-based superconducting materials AkCa_(2)Fe_(4)As_(4)F_(2)(Ak=K,Rb,Cs)systems based on the block-layer model and explored their relationship with Tc.We observed that an increase in interlayer combinative energy leads to a decrease in Tc,while conversely,a decrease in interlayer combination energy results in an increase in Tc.Further,we found that the contribution of the Fe 3d band structure,especially the 3dz2 orbital,to charge transfer is significant.展开更多
Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect ...Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.展开更多
The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to...The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.展开更多
A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the mol...A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the molten salt reactor and power system.This model considers the impact of thermal properties of fluid variation on accuracy and has been validated with Simulink.This study reveals the capability of the control system to compensate for anomalous situations and maintain shaft stability in the event of perturbations occurring in high-temperature molten salt tank outlet parameters.Meanwhile,the control system’s impact on the system’s dynamic characteristics under molten salt disturbance is also analyzed.The results reveal that after the disturbance occurs,the controlled system benefits from the action of the control,and the overshoot and disturbance amplitude are positively correlated,while the system power and frequency eventually return to the initial values.This simulation model provides a basis for utilizing molten salt reactors for power generation and maintaining grid stability.展开更多
Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a com...Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.展开更多
Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the inves...Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the investigation of the mechanical response,failure mode,instability assessment criteria,and anchorage effect of AS subjected to combined cyclic dynamic-static triaxial stress paths.The results show that the peak bearing strength is positively correlated with the anchoring matrix strength,anchorage length,and edgewise compressive strength.The bearing capacity decreases significantly when the anchorage direction is severely inclined.The free face failure modes are typically transverse cracking,concave fracturing,V-shaped slipping and detachment,and spallation detachment.Besides,when the anchoring matrix strength and the anchorage length decrease while the edgewise compressive strength,loading rate,and anchorage inclination angle increase,the failure intensity rises.Instability is determined by a negative tangent modulus of the displacement-strength curve or the continued deformation increase against the general downward trend.Under cyclic loads,the driving force that breaks the rock mass along the normal vector and the rigidity of the AS are the two factors that determine roadway stability.Finally,a control measure for surrounding rock stability is proposed to reduce the internal driving force via a pressure relief method and improve the rigidity of the AS by full-length anchorage and grouting modification.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monocl...Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.展开更多
Simultaneous stresses of salinity and drought often coincide during rice-growing seasons in saline lands,primarily due to insufficient water resources and inadequate irrigation facilities.Consequently,combined salinit...Simultaneous stresses of salinity and drought often coincide during rice-growing seasons in saline lands,primarily due to insufficient water resources and inadequate irrigation facilities.Consequently,combined salinity-drought stress poses a major threat to rice production.In this study,two salinity levels(NS,non-salinity;HS,high salinity)along with three drought treatments(CC,control condition;DJ,drought stress imposed at jointing;DH,drought stress imposed at heading)were performed to investigate their combined influences on leaf photosynthetic characteristics,biomass accumulation,and rice yield formation.Salinity,drought,and their combination led to a shortened growth period from heading to maturity,resulting in a reduced overall growth duration.Grain yield was reduced under both salinity and drought stress,with a more substantial reduction under the combined salinity-drought stress.The combined stress imposed at heading caused greater yield losses in rice compared with the stress imposed at jointing.Additionally,the combined salinity-drought stress induced greater decreases in shoot biomass accumulation from heading to maturity,as well as in shoot biomass and nonstructural carbohydrate(NSC)content in the stem at heading and maturity.However,it increased the harvest index and NSC remobilization reserve.Salinity and drought reduced the leaf area index and SPAD value of flag leaves and weakened the leaf photosynthetic characteristics as indicated by lower photosynthetic rates,transpiration rates,and stomatal conductance.These reductions were more pronounced under the combined stress.Salinity,drought,and especially their combination,decreased the activities of ascorbate peroxidase,catalase,and superoxide dismutase,while increasing the contents of malondialdehyde,hydrogen peroxide,and superoxide radical.Our results indicated a more significant yield loss in rice when subjected to combined salinity-drought stress.The individual and combined stresses of salinity and drought diminished antioxidant enzyme activities,inhibited leaf photosynthetic functions,accelerated leaf senescence,and subsequently lowered assimilate accumulation and grain yield.展开更多
BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erl...BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.展开更多
To meet the goal of worldwide decarbonization,the transformation process toward clean and green energy structures has accelerated.In this context,coal-fired power plant(CFPP)and large-scale energy storage represented ...To meet the goal of worldwide decarbonization,the transformation process toward clean and green energy structures has accelerated.In this context,coal-fired power plant(CFPP)and large-scale energy storage represented by compressed air energy storage(CAES)technology,are tasked with increasing renewable resource accommodation and maintaining the power system security.To achieve this,this paper proposes the concept of a CFPP-CAES combined cycle and a trigenerative system based on that.Considering the working conditions of the CFPP,thermal characteristics of three typical operation modes were studied and some general regularities were identified.The results of various potential integration schemes discussion indicated that extracting water from low-temperature points in the feedwater system to cool pressurized air and simultaneously increase the backwater temperature is beneficial for improving performance.In addition,preheating the pressurized air before the air expanders via lowgrade water in the feedwater system as much as possible and reducing extracted steam contribute to increasing the efficiency.With the optimal integration scheme,2.85 tonnes of coal can be saved per cycle and the round-trip efficiency can be increased by 2.24%.Through the cogeneration of heat and power,the system efficiency can reach 77.5%.In addition,the contribution degree of the three compression heat utilization methods to the performance improvement ranked from high to low,is preheating the feedwater before the boiler,supplying heat,and flowing into the CFPP feedwater system.In the cooling energy generation mode,the system efficiency can be increased to over 69%.Regardless of the operation mode,the benefit produced by integration is further enhanced when the CFPP operates at higher operating conditions because the coupling points parameters are changed.In addition,the dynamic payback period can be shortened by 11.33 years and the internal rate of return increases by 5.20%under a typical application scenario.Regarding the effect of different application scenarios in terms of economics,investing in the proposed system is more appropriate in regions with multiple energy demands,especially heating demand.These results demonstrate the technical advantages of the proposed system and provide guiding principles for its design,operation,and project investment.展开更多
The shear mechanical behavior is regarded as an essential factor affecting the stability of the surrounding rocks in underground engineering.The shear strength and failure mechanisms of layered rock are significantly ...The shear mechanical behavior is regarded as an essential factor affecting the stability of the surrounding rocks in underground engineering.The shear strength and failure mechanisms of layered rock are significantly affected by the foliation angles.Direct shear tests were conducted on cubic slate samples with foliation angles of 0°,30°,45°,60°,and 90°.The effect of foliation angles on failure patterns,acoustic emission(AE)characteristics,and shear strength parameters was analyzed.Based on AE characteristics,the slate failure process could be divided into four stages:quiet period,step-like increasing period,dramatic increasing period,and remission period.A new empirical expression of cohesion for layered rock was proposed,which was compared with linear and sinusoidal cohesion expressions based on the results made by this paper and previous experiments.The comparative analysis demonstrated that the new expression has better prediction ability than other expressions.The proposed empirical equation was used for direct shear simulations with the combined finite-discrete element method(FDEM),and it was found to align well with the experimental results.Considering both computational efficiency and accuracy,it was recommended to use a shear rate of 0.01 m/s for FDEM to carry out direct shear simulations.To balance the relationship between the number of elements and the simulation results in the direct shear simulations,the recommended element size is 1 mm.展开更多
BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate i...BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.展开更多
BACKGROUND Preschoolers become anxious when they are about to undergo anesthesia and surgery,warranting the development of more appropriate and effective interventions.AIM To explore the effect of static cartoons comb...BACKGROUND Preschoolers become anxious when they are about to undergo anesthesia and surgery,warranting the development of more appropriate and effective interventions.AIM To explore the effect of static cartoons combined with dynamic virtual environments on preoperative anxiety and anesthesia induction compliance in preschool-aged children undergoing surgery.METHODS One hundred and sixteen preschool-aged children were selected and assigned to the drug(n=37),intervention(n=40),and control(n=39)groups.All the children received routine preoperative checkups and nursing before being transferred to the preoperative preparation room on the day of the operation.The drug group received 0.5 mg/kg midazolam and the intervention group treatment consisting of static cartoons combined with dynamic virtual environments.The control group received no intervention.The modified Yale Preoperative Anxiety Scale was used to evaluate the children’s anxiety level on the day before surgery(T0),before leaving the preoperative preparation room(T1),when entering the operating room(T2),and at anesthesia induction(T3).Compliance during anesthesia induction(T3)was evaluated using the Induction Compliance Checklist(ICC).Changes in mean arterial pressure(MAP),heart rate(HR),and respiratory rate(RR)were also recorded at each time point.RESULTS The anxiety scores of the three groups increased variously at T1 and T2.At T3,both the drug and intervention groups had similar anxiety scores,both of which were lower than those in the control group.At T1 and T2,MAP,HR,and RR of the three groups increased.The drug and control groups had significantly higher MAP and RR than the intervention group at T2.At T3,the MAP,HR,and RR of the drug group decreased and were significantly lower than those in the control group but were comparable to those in the intervention group.Both the drug and intervention groups had similar ICC scores and duration of anesthesia induction(T3),both of which were higher than those of the control group.CONCLUSION Combining static cartoons with dynamic virtual environments as effective as medication,specifically midazolam,in reducing preoperative anxiety and fear in preschool-aged children.This approach also improve their compliance during anesthesia induction and helped maintain their stable vital signs.展开更多
Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome ...Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.展开更多
In the coastal environment,the co-occurrence of antibiotic and nanoplastic pollution is common.Investigating their individual and combined toxicity to marine organisms is of great necessity.In the present study,the re...In the coastal environment,the co-occurrence of antibiotic and nanoplastic pollution is common.Investigating their individual and combined toxicity to marine organisms is of great necessity.In the present study,the reproductive toxicity of sulfamethazine(SMZ)and nanoplastics(polystyrene,PS)via the dietary route on the spermatogenesis of marine medaka(Oryzias melastigma)was examined.After 30 d of dietary exposure,SMZ alone decreased the gonadosomatic index(GSI)value(~35%)and the proportion of undifferentiated type A spermatogonia(A_(und))(~40%),probably by disrupting the testicular sex hormone production,the spermatogenesis-related growth factor network and the balance of apoptosis.Individual exposure to PS did not affect the GSI value or the proportions of germ cells at different developmental stages,but dysregulated the expression of several spermatogenesis-related genes.Interestingly,the presence of PS alleviated the decreased GSI value caused by SMZ.This alleviation effect was achieved by enhancing the spermatogonia differentiation instead of reversing the suppressed self-renewal of A_(und),suggesting that the mixture of PS and SMZ could cause reproductive effects in a different way.These findings expand our knowledge of threats of ubiquitous antibiotic and nanoplastic pollution to fish reproduction and population.展开更多
Complete and comprehensive information about sediment dynamic and identification of hotspots of sediment production and transport are necessary for understanding the erosion processes and increasing the efficiency of ...Complete and comprehensive information about sediment dynamic and identification of hotspots of sediment production and transport are necessary for understanding the erosion processes and increasing the efficiency of soil and water conservation practices.Numerous studies used the sediment fingerprint techniques to investigate the contribution of different sources in suspended and bed sediment yield of the watersheds.However,the contribution of various land use/land covers in suspended and bed sediment yield for the great Caspian Sea basin is in an aura of ambiguity and the present study was conducted to gather information about an important part of this area in northern Iran,where rangelands are located upstream of Hyrcanian forests and dense agricultural lands are located downstream.The surface soil of different land use/land covers including forest,rangeland,agriculture and streambank lands were sampled in 30 points.Suspended and bed sediments were sampled in the watershed outlet in two high and low water periods.Geochemical characteristics of soil and sediment samples containing 59 elements were measured using ICP-OES GBC Integra.The reliable and suitable tracers from 59 elements were then selected using Range test,Kruskal-Wallis and Discriminant Function Analysis,respectively,in FingerPro package of R software.The results showed that for suspended sediment,streambank and rangeland had the highest contributions of 86.2%and 47.5%,respectively,in two high and low water periods.For bed sediment,in two high and low water periods,rangeland and streambank had the highest contributions of 73.8%and 84.4%,respectively.Land use change and especially human activities such as agriculture,road construction and development of residential areas along the main river riparian zone has led to a significant increase in suspended and bed sediments.展开更多
An ultrafast framing camera with a pulse-dilation device,a microchannel plate(MCP)imager,and an electronic imaging system were reported.The camera achieved a temporal resolution of 10 ps by using a pulse-dilation devi...An ultrafast framing camera with a pulse-dilation device,a microchannel plate(MCP)imager,and an electronic imaging system were reported.The camera achieved a temporal resolution of 10 ps by using a pulse-dilation device and gated MCP imager,and a spatial resolution of 100μm by using an electronic imaging system comprising combined magnetic lenses.The spatial resolution characteristics of the camera were studied both theoretically and experimentally.The results showed that the camera with combined magnetic lenses reduced the field curvature and acquired a larger working area.A working area with a diameter of 53 mm was created by applying four magnetic lenses to the camera.Furthermore,the camera was used to detect the X-rays produced by the laser-targeting device.The diagnostic results indicated that the width of the X-ray pulse was approximately 18 ps.展开更多
基金financial support from National Key Research and Development Program(2017YFD0501403)National Natural Science Foundation of China(Nos.81872819)+4 种基金Natural Science Foundation of Jiangsu Province(No.BK20171390)supported by Double First-Rate construction plan of China Pharmaceutical University(CPU2018GY26)the Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.SKLNMZZCX201816)the National Science and Technology Major Project(2017ZX09101001)the financial support from Development Funds for Priority Academic Programs in Jiangsu Higher Education Institutions-Young Talent Program。
文摘Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs.Herein,chitosan conjugates(SPCS)installed with sialic acid(SA)and phenylboronic acid(PBA)were synthesized,of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA.The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges.The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract.After reaching the lesions,the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release,while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside.The drugmicelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation.The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable,safe and flexible anti-infectious drug delivery systems.
文摘Superconducting transition temperature(Tc),as a crucial parameter,exploring its relationship with various macroscopic and microscopic factors helps to understand the mechanism of high-temperature superconductivity from multiple perspectives,aiding in a multidimensional comprehension of high-temperature superconductivity mechanisms.Drawing inspiration from the block-layer structure models of cuprate superconductors,we computationally investigated the interlayer interaction energies in the 12442-type iron-based superconducting materials AkCa_(2)Fe_(4)As_(4)F_(2)(Ak=K,Rb,Cs)systems based on the block-layer model and explored their relationship with Tc.We observed that an increase in interlayer combinative energy leads to a decrease in Tc,while conversely,a decrease in interlayer combination energy results in an increase in Tc.Further,we found that the contribution of the Fe 3d band structure,especially the 3dz2 orbital,to charge transfer is significant.
基金supported by the grants from Shanghai Shuguang Plan Project,No.18SG15(to SC)Shanghai Outstanding Young Scholars Project+2 种基金Shanghai Talent Development Project,No.2019044(to SC)Medical-engineering cross fund of Shanghai Jiao Tong University,No.YG2022QN009(to QZ)the National Natural Science Foundation of China,No.82201558(to QZ)。
文摘Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.
文摘The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.
基金This work was supported by the Chinese TMSR Strategic Pioneer Science and Technology Project(No.XDA02010300).
文摘A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the molten salt reactor and power system.This model considers the impact of thermal properties of fluid variation on accuracy and has been validated with Simulink.This study reveals the capability of the control system to compensate for anomalous situations and maintain shaft stability in the event of perturbations occurring in high-temperature molten salt tank outlet parameters.Meanwhile,the control system’s impact on the system’s dynamic characteristics under molten salt disturbance is also analyzed.The results reveal that after the disturbance occurs,the controlled system benefits from the action of the control,and the overshoot and disturbance amplitude are positively correlated,while the system power and frequency eventually return to the initial values.This simulation model provides a basis for utilizing molten salt reactors for power generation and maintaining grid stability.
文摘Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
基金This paper is financially supported by the National Natural Science Foundation of China(Grant Nos.52074263 and 52034007)the Postgraduate Research and Practice Innovation Program of Jiangsu Province(Grant No.KYCX21_2332).
文摘Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the investigation of the mechanical response,failure mode,instability assessment criteria,and anchorage effect of AS subjected to combined cyclic dynamic-static triaxial stress paths.The results show that the peak bearing strength is positively correlated with the anchoring matrix strength,anchorage length,and edgewise compressive strength.The bearing capacity decreases significantly when the anchorage direction is severely inclined.The free face failure modes are typically transverse cracking,concave fracturing,V-shaped slipping and detachment,and spallation detachment.Besides,when the anchoring matrix strength and the anchorage length decrease while the edgewise compressive strength,loading rate,and anchorage inclination angle increase,the failure intensity rises.Instability is determined by a negative tangent modulus of the displacement-strength curve or the continued deformation increase against the general downward trend.Under cyclic loads,the driving force that breaks the rock mass along the normal vector and the rigidity of the AS are the two factors that determine roadway stability.Finally,a control measure for surrounding rock stability is proposed to reduce the internal driving force via a pressure relief method and improve the rigidity of the AS by full-length anchorage and grouting modification.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
文摘Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.
基金financed by the National Key Research and Development Program,China(Grant Nos.2022YFE0113400 and 2022YFD1500402)National Natural Science Foundation of China(Grant No.32001466)+3 种基金Scientific and Technological Innovation Fund of Carbon Emissions Peak and Neutrality of Jiangsu Provincial Department of Science and Technology,China(Grant Nos.BE2022304 and BE2022305)Joints Funds of the National Natural Science Foundation of China(Grant No.U20A2022)Postdoctoral Research Foundation of China(Grant No.2020M671628)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China.
文摘Simultaneous stresses of salinity and drought often coincide during rice-growing seasons in saline lands,primarily due to insufficient water resources and inadequate irrigation facilities.Consequently,combined salinity-drought stress poses a major threat to rice production.In this study,two salinity levels(NS,non-salinity;HS,high salinity)along with three drought treatments(CC,control condition;DJ,drought stress imposed at jointing;DH,drought stress imposed at heading)were performed to investigate their combined influences on leaf photosynthetic characteristics,biomass accumulation,and rice yield formation.Salinity,drought,and their combination led to a shortened growth period from heading to maturity,resulting in a reduced overall growth duration.Grain yield was reduced under both salinity and drought stress,with a more substantial reduction under the combined salinity-drought stress.The combined stress imposed at heading caused greater yield losses in rice compared with the stress imposed at jointing.Additionally,the combined salinity-drought stress induced greater decreases in shoot biomass accumulation from heading to maturity,as well as in shoot biomass and nonstructural carbohydrate(NSC)content in the stem at heading and maturity.However,it increased the harvest index and NSC remobilization reserve.Salinity and drought reduced the leaf area index and SPAD value of flag leaves and weakened the leaf photosynthetic characteristics as indicated by lower photosynthetic rates,transpiration rates,and stomatal conductance.These reductions were more pronounced under the combined stress.Salinity,drought,and especially their combination,decreased the activities of ascorbate peroxidase,catalase,and superoxide dismutase,while increasing the contents of malondialdehyde,hydrogen peroxide,and superoxide radical.Our results indicated a more significant yield loss in rice when subjected to combined salinity-drought stress.The individual and combined stresses of salinity and drought diminished antioxidant enzyme activities,inhibited leaf photosynthetic functions,accelerated leaf senescence,and subsequently lowered assimilate accumulation and grain yield.
基金Supported by NIH/National Cancer Institute Grant,No.R01CA138441 and No.R01CA269452UW Madison Centene Pancreas Cancer Collaborative Award,No.21-8568.
文摘BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.
文摘To meet the goal of worldwide decarbonization,the transformation process toward clean and green energy structures has accelerated.In this context,coal-fired power plant(CFPP)and large-scale energy storage represented by compressed air energy storage(CAES)technology,are tasked with increasing renewable resource accommodation and maintaining the power system security.To achieve this,this paper proposes the concept of a CFPP-CAES combined cycle and a trigenerative system based on that.Considering the working conditions of the CFPP,thermal characteristics of three typical operation modes were studied and some general regularities were identified.The results of various potential integration schemes discussion indicated that extracting water from low-temperature points in the feedwater system to cool pressurized air and simultaneously increase the backwater temperature is beneficial for improving performance.In addition,preheating the pressurized air before the air expanders via lowgrade water in the feedwater system as much as possible and reducing extracted steam contribute to increasing the efficiency.With the optimal integration scheme,2.85 tonnes of coal can be saved per cycle and the round-trip efficiency can be increased by 2.24%.Through the cogeneration of heat and power,the system efficiency can reach 77.5%.In addition,the contribution degree of the three compression heat utilization methods to the performance improvement ranked from high to low,is preheating the feedwater before the boiler,supplying heat,and flowing into the CFPP feedwater system.In the cooling energy generation mode,the system efficiency can be increased to over 69%.Regardless of the operation mode,the benefit produced by integration is further enhanced when the CFPP operates at higher operating conditions because the coupling points parameters are changed.In addition,the dynamic payback period can be shortened by 11.33 years and the internal rate of return increases by 5.20%under a typical application scenario.Regarding the effect of different application scenarios in terms of economics,investing in the proposed system is more appropriate in regions with multiple energy demands,especially heating demand.These results demonstrate the technical advantages of the proposed system and provide guiding principles for its design,operation,and project investment.
基金support from the Natural Science Foundation of China(Grant Nos.41941018,U21A20153,42177140).
文摘The shear mechanical behavior is regarded as an essential factor affecting the stability of the surrounding rocks in underground engineering.The shear strength and failure mechanisms of layered rock are significantly affected by the foliation angles.Direct shear tests were conducted on cubic slate samples with foliation angles of 0°,30°,45°,60°,and 90°.The effect of foliation angles on failure patterns,acoustic emission(AE)characteristics,and shear strength parameters was analyzed.Based on AE characteristics,the slate failure process could be divided into four stages:quiet period,step-like increasing period,dramatic increasing period,and remission period.A new empirical expression of cohesion for layered rock was proposed,which was compared with linear and sinusoidal cohesion expressions based on the results made by this paper and previous experiments.The comparative analysis demonstrated that the new expression has better prediction ability than other expressions.The proposed empirical equation was used for direct shear simulations with the combined finite-discrete element method(FDEM),and it was found to align well with the experimental results.Considering both computational efficiency and accuracy,it was recommended to use a shear rate of 0.01 m/s for FDEM to carry out direct shear simulations.To balance the relationship between the number of elements and the simulation results in the direct shear simulations,the recommended element size is 1 mm.
文摘BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.
基金Supported by Hangzhou Medical and Health Technology Project,No.OO20191141。
文摘BACKGROUND Preschoolers become anxious when they are about to undergo anesthesia and surgery,warranting the development of more appropriate and effective interventions.AIM To explore the effect of static cartoons combined with dynamic virtual environments on preoperative anxiety and anesthesia induction compliance in preschool-aged children undergoing surgery.METHODS One hundred and sixteen preschool-aged children were selected and assigned to the drug(n=37),intervention(n=40),and control(n=39)groups.All the children received routine preoperative checkups and nursing before being transferred to the preoperative preparation room on the day of the operation.The drug group received 0.5 mg/kg midazolam and the intervention group treatment consisting of static cartoons combined with dynamic virtual environments.The control group received no intervention.The modified Yale Preoperative Anxiety Scale was used to evaluate the children’s anxiety level on the day before surgery(T0),before leaving the preoperative preparation room(T1),when entering the operating room(T2),and at anesthesia induction(T3).Compliance during anesthesia induction(T3)was evaluated using the Induction Compliance Checklist(ICC).Changes in mean arterial pressure(MAP),heart rate(HR),and respiratory rate(RR)were also recorded at each time point.RESULTS The anxiety scores of the three groups increased variously at T1 and T2.At T3,both the drug and intervention groups had similar anxiety scores,both of which were lower than those in the control group.At T1 and T2,MAP,HR,and RR of the three groups increased.The drug and control groups had significantly higher MAP and RR than the intervention group at T2.At T3,the MAP,HR,and RR of the drug group decreased and were significantly lower than those in the control group but were comparable to those in the intervention group.Both the drug and intervention groups had similar ICC scores and duration of anesthesia induction(T3),both of which were higher than those of the control group.CONCLUSION Combining static cartoons with dynamic virtual environments as effective as medication,specifically midazolam,in reducing preoperative anxiety and fear in preschool-aged children.This approach also improve their compliance during anesthesia induction and helped maintain their stable vital signs.
基金supported by the Natural Science Foundation of China(Grant Nos.:22225702 and 32322048)the National Key R&D Program of China(Grant No.:2020YFE0202200)+8 种基金the Shanghai Academic/Technology Research Leader Program,China(Grant No.:22XD1420900)Guangdong High-level New R&D Institute,China(Grant No.:2019B090904008)Guangdong High-level Innovative Research Institute,China(Grant No.:2021B0909050003)the Shanghai Rising-Star Program,China(Grant No.:22QA1411100)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.:2021276)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology,China(Grant No.:2022QNRC001)the open fund of State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,China(Grant No.:KF-202201)We also thank the support of the Innovative Research Team of High-Level Local Universities in Shanghai,China(Grant No.:SHSMU-ZDCX20212700)Sanofi scholarship program.
文摘Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.
基金The National Natural Science Foundation of China under contract No.42106119the Department of Science and Technology of Fujian Province under contract Nos 2022J02052,2020J05175 and 2020J05178+1 种基金the Fujian Provincial Department of Ocean and Fisheries under contract No.FJHJF-L-2022-12the Yancheng Fishery High Quality Development Project under contract No.YCSCYJ2021023.
文摘In the coastal environment,the co-occurrence of antibiotic and nanoplastic pollution is common.Investigating their individual and combined toxicity to marine organisms is of great necessity.In the present study,the reproductive toxicity of sulfamethazine(SMZ)and nanoplastics(polystyrene,PS)via the dietary route on the spermatogenesis of marine medaka(Oryzias melastigma)was examined.After 30 d of dietary exposure,SMZ alone decreased the gonadosomatic index(GSI)value(~35%)and the proportion of undifferentiated type A spermatogonia(A_(und))(~40%),probably by disrupting the testicular sex hormone production,the spermatogenesis-related growth factor network and the balance of apoptosis.Individual exposure to PS did not affect the GSI value or the proportions of germ cells at different developmental stages,but dysregulated the expression of several spermatogenesis-related genes.Interestingly,the presence of PS alleviated the decreased GSI value caused by SMZ.This alleviation effect was achieved by enhancing the spermatogonia differentiation instead of reversing the suppressed self-renewal of A_(und),suggesting that the mixture of PS and SMZ could cause reproductive effects in a different way.These findings expand our knowledge of threats of ubiquitous antibiotic and nanoplastic pollution to fish reproduction and population.
基金the doctoral dissertation of Nabiyeh Karimi with the financial support of Sari University of Agricultural Sciences and Natural Resources, Iran
文摘Complete and comprehensive information about sediment dynamic and identification of hotspots of sediment production and transport are necessary for understanding the erosion processes and increasing the efficiency of soil and water conservation practices.Numerous studies used the sediment fingerprint techniques to investigate the contribution of different sources in suspended and bed sediment yield of the watersheds.However,the contribution of various land use/land covers in suspended and bed sediment yield for the great Caspian Sea basin is in an aura of ambiguity and the present study was conducted to gather information about an important part of this area in northern Iran,where rangelands are located upstream of Hyrcanian forests and dense agricultural lands are located downstream.The surface soil of different land use/land covers including forest,rangeland,agriculture and streambank lands were sampled in 30 points.Suspended and bed sediments were sampled in the watershed outlet in two high and low water periods.Geochemical characteristics of soil and sediment samples containing 59 elements were measured using ICP-OES GBC Integra.The reliable and suitable tracers from 59 elements were then selected using Range test,Kruskal-Wallis and Discriminant Function Analysis,respectively,in FingerPro package of R software.The results showed that for suspended sediment,streambank and rangeland had the highest contributions of 86.2%and 47.5%,respectively,in two high and low water periods.For bed sediment,in two high and low water periods,rangeland and streambank had the highest contributions of 73.8%and 84.4%,respectively.Land use change and especially human activities such as agriculture,road construction and development of residential areas along the main river riparian zone has led to a significant increase in suspended and bed sediments.
基金National Natural Science Foundation of China(NSFC)(No.11775147)Guangdong Basic and Applied Basic Research Foundation(Nos.2019A1515110130 and 2024A1515011832)+1 种基金Shenzhen Key Laboratory of Photonics and Biophotonics(ZDSYS20210623092006020)Shenzhen Science and Technology Program(Nos.JCYJ20210324095007020,JCYJ20200109105201936 and JCYJ20230808105019039).
文摘An ultrafast framing camera with a pulse-dilation device,a microchannel plate(MCP)imager,and an electronic imaging system were reported.The camera achieved a temporal resolution of 10 ps by using a pulse-dilation device and gated MCP imager,and a spatial resolution of 100μm by using an electronic imaging system comprising combined magnetic lenses.The spatial resolution characteristics of the camera were studied both theoretically and experimentally.The results showed that the camera with combined magnetic lenses reduced the field curvature and acquired a larger working area.A working area with a diameter of 53 mm was created by applying four magnetic lenses to the camera.Furthermore,the camera was used to detect the X-rays produced by the laser-targeting device.The diagnostic results indicated that the width of the X-ray pulse was approximately 18 ps.
