Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke,...Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.展开更多
Aberrant changes in the gut microbiota are implicated in many diseases,including inflammatory bowel disease(IBD).Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barr...Aberrant changes in the gut microbiota are implicated in many diseases,including inflammatory bowel disease(IBD).Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity,indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD.Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies,novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed.Herein,we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone(an enantiomer)as a potent agent against experimental colitis that acts by modulating the gut microbiota.5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids(SCFAs);thus,it regulates the intestinal immune system by reducing proinflammatory immune cell numbers,and maintains intestinal mucosal integrity by modulating tight junctions(TJs).Moreover,5S-heudelotinone(2)ameliorates colitis-associated colorectal cancer(CAC)in an azoxymethane(AOM)/dextran sulfate sodium(DSS)-induced in situ carcinoma model.Together,these findings reveal the potential of a novel natural product,namely,5S-heudelotinone,to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.展开更多
Endothelial cells(ECs)form a single cell layer that lines the inner surface of all blood and lymphatic vessels,acting as the barrier between vessels and underlying tissues.ECs are not only responsible for the flow of ...Endothelial cells(ECs)form a single cell layer that lines the inner surface of all blood and lymphatic vessels,acting as the barrier between vessels and underlying tissues.ECs are not only responsible for the flow of substances and fluid into and out of tissues but are also involved in many processes,such as coagulation,fibrinolysis,and regulation of vascular tone and inflammation.展开更多
Objectives:This study aims to not only investigate the prevalence of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer but also identify the contributing factors.Materials a...Objectives:This study aims to not only investigate the prevalence of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer but also identify the contributing factors.Materials and methods:A total of 245 elderly patients diagnosed with prostate cancer and undergoing radical prostatectomy at a tertiary care general hospital in Jinan were included in this study.To assess the patients,several questionnaires were used.These included the General Situation Questionnaire,General Alienation Scale,Social Impact Scale,Modified Memorial Anxiety Scale for Prostate Cancer,and Perceived Social Support Scale.Pearson correlation analysis was conducted to examine the relationships between variables,whereas multiple linear regression was used to identify the factors influencing social alienation among patients who underwent radical prostatectomy.Results:Patients who underwent radical prostatectomy had a mean total score of 44.13±7.24 on the Social Alienation Scale.The results of the Pearson correlation analysis indicated that social alienation showed an inverse association with social support(r=−0.627,p<0.05)and positive associations with age,disease stigma,and anxiety(r=0.325,0.575,0.421,all p’s<0.01)among patients who underwent radical prostatectomy.The findings frommultiple linear regression analysis demonstrated that educational level,age,urinary incontinence,disease stigma,anxiety,and social support significantly influenced social alienation among elderly patients who underwent radical prostatectomy(p<0.05).Conclusions:Elderly patients who undergo radical prostatectomy often experience social alienation.This study found that social alienation was associated with factors such as educational level,age,urinary incontinence,social support,anxiety,and disease stigma.Consequently,healthcare providers should actively monitor the degree of social alienation in elderly patients after radical prostatectomy and provide suitable psychological care to facilitate positive social reintegration and alleviate their feelings of social alienation.展开更多
Objective:To analyze the impact of meteorological factors on the incidence of influenza based on the Yunqi theory in Beijing area,and to establish an effective forecast modelMethods:Monthly data on the incidence of in...Objective:To analyze the impact of meteorological factors on the incidence of influenza based on the Yunqi theory in Beijing area,and to establish an effective forecast modelMethods:Monthly data on the incidence of influenza from 1970 to 2004 and daily data on the meteorological factors (including daily averages of temperature,wind speed,relative humidity,vapor pressure,and daily total precipitation) from 1966 to 2004 were collected and processed under the traditional Chinese medicine (TCM) theory of six qi.A back-propagation artificial neural network was then performed to analyze the data.Results:The highest incidence of influenza occurs in the sixth qi (the period of December and January),which is characterized by dryness and coldness.Altogether six models were successfully established.Climatic data used were of the same year,one year prior,two years prior,and three years prior to the influenza data respectively.The last two models involve climatic data of the previous three years plus the current year and of the past four years plus the current year.Finally,we determined the fifth model has the highest forecast accuracy (49%).Conclusions:Meteorological factors can exert an influence on the incidence of influenza,which corresponds to TCM theory that 'the pestilence occurred three years after the abnormal climatic changes'.This study may generate interest among the public health community and other TCM theories can be applied so that public health measures can be taken to prevent and control influenza,particularly during the winter months.展开更多
In cloud storage,client-side deduplication is widely used to reduce storage and communication costs.In client-side deduplication,if the cloud server detects that the user’s outsourced data have been stored,then clien...In cloud storage,client-side deduplication is widely used to reduce storage and communication costs.In client-side deduplication,if the cloud server detects that the user’s outsourced data have been stored,then clients will not need to reupload the data.However,the information on whether data need to be uploaded can be used as a side-channel,which can consequently be exploited by adversaries to compromise data privacy.In this paper,we propose a new threat model against side-channel attacks.Different from existing schemes,the adversary could learn the approximate ratio of stored chunks to unstored chunks in outsourced files,and this ratio will affect the probability that the adversary compromises the data privacy through side-channel attacks.Under this threat model,we design two defense schemes to minimize privacy leakage,both of which design interaction protocols between clients and the server during deduplication checks to reduce the probability that the adversary compromises data privacy.We analyze the security of our schemes,and evaluate their performances based on a real-world dataset.Compared with existing schemes,our schemes can better mitigate data privacy leakage and have a slightly lower communication cost.展开更多
While users enjoy the convenience of data outsourcing in the cloud,they also face the risks of data modification and private information leakage.Searchable encryption technology can perform keyword searches over encry...While users enjoy the convenience of data outsourcing in the cloud,they also face the risks of data modification and private information leakage.Searchable encryption technology can perform keyword searches over encrypted data while protecting their privacy and guaranteeing the integrity of the data by verifying the search results.However,some associated problems are still encountered,such as the low efficiency of verification and uncontrollable query results.Accordingly,this paper proposes a Privacy-Preserving Searchable Encryption(PPSE)scheme based on public and private blockchains.First,we store an encrypted index in a private blockchain while outsourcing corresponding encrypted documents to a public blockchain.The encrypted documents are located through the encrypted index.This method can reduce the storage overhead on the blockchains,and improve the efficiency of transaction execution and the security of stored data.Moreover,we adopt a smart contract to introduce a secondary verification access control mechanism and restrict data users’access to the private blockchain through authorization for the purpose of guaranteeing data privacy and the correctness of access control verification.Finally,the security analysis and experimental results indicate that compared with existing schemes,the proposed scheme can not only improve the security of encrypted data but also guarantee the efficiency of the query.展开更多
Carbon cycle is one of the focuses of climate change, river carbon is an important part, while dissolved inorganic carbon (DIC) has a high proportion of river carbon flux. In this study, we did the research on the Lan...Carbon cycle is one of the focuses of climate change, river carbon is an important part, while dissolved inorganic carbon (DIC) has a high proportion of river carbon flux. In this study, we did the research on the Lancang River, an important international river in the southwest of China. Water samples were obtained from 16 sections of the middle and lower reaches of the Lancang River in 2016 (11 months), then we monitored some water quality indicators and DIC content, finally analyzed the temporal-spatial distribution characteristics of DIC and the relationship between DIC content and water environment factors. The results showed that: (1) DIC contents in the middle and lower reaches of the Lancang River varied from 1.1840 mmol/L to 3.1440 mmol/L, with a mean value of about 2.2155 mmol/L. (2) At a time scale, DIC contents of dry season (spring, autumn and winter) were higher than rainy season (summer). At a space scale, DIC contents of the middle and lower reaches of the Lancang River gradually decreased from north to south, and each reservoir had the same characteristics, that is, DIC contents at upstream of the dam was lower than those at downstream of the dam. Compared to other rivers with cascade dams around the world, DIC contents within studied river were at similar level. And the reservoir’s effect of the Lancang River were not obvious, however, DIC contents in the water sampled upstream the dams had a slight stratification. (3) Water temperature, conductivity, turbidity were important factors affecting DIC content of water, and the effect of oxidation and reduction potential (ORP) and pH on DIC was relatively small.展开更多
Immobilized microbial technology has been widely used in wastewater treatment,but it has been used less frequently for soil remediation,particularly in sites that are co-contaminated with organic compounds and heavy m...Immobilized microbial technology has been widely used in wastewater treatment,but it has been used less frequently for soil remediation,particularly in sites that are co-contaminated with organic compounds and heavy metals.In addition,there is limited knowledge on the efficiency of remediation and microbial preferences to colonize the immobilized carriers.In this study,biochar immobilized with Sphingobium abikonense was introduced to remediate soils that were co-contaminated with phenanthrene(PHE)and copper(Cu),and the mechanisms of microbial assemblage were investigated.The immobilized microbial biochar maintained a degradation rate of more than 96%in both the first(0-6 d)and second(6-12 d)contamination periods.The addition of biochar increased the proportion of Cu bound to organic matter,and Fe-Mn oxide bound Cu in the soil.In addition,both Cu and PHE could be adsorbed into biochar pellets in the presence or absence of immobilized S.abikonense.The presence of biochar significantly increased the abundance of bacteria,such as Luteibacter,Bordetella and Dyella,that could degrade organic matter and tolerate heavy metals.Notably,the biochar could specifically select host microbes from the soil for colonization,while the presence of S.abikonense affected this preference.The autonomous selection facilitates the degradation of PHE and/or the immobilization of Cu in the soil.These results provide a green approach to efficiently and sustainably remediate soil co-contaminated with PHE and Cu and highlight the importance of microbial preference colonized in immobilized carriers.展开更多
Summary What is already known about this topic?In December 2022,China revised its epidemic prevention and control strategy,leading to an increase in coronavirus disease 2019(COVID-19)cases and a peak in medical consul...Summary What is already known about this topic?In December 2022,China revised its epidemic prevention and control strategy,leading to an increase in coronavirus disease 2019(COVID-19)cases and a peak in medical consultations.Government departments implemented relevant policies to coordinate and allocate medical resources throughout China.However,there is a scarcity of research on the status of medical consultations and the factors influencing them.展开更多
Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammat...Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administration significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.展开更多
The integration of building information modeling(BIM)and lean construction(LC)provides a solution for the management of megaprojects.Previous studies have generally focused on the theoretical or empirical adoption of ...The integration of building information modeling(BIM)and lean construction(LC)provides a solution for the management of megaprojects.Previous studies have generally focused on the theoretical or empirical adoption of BIM and LC.Moreover,only a few studies have examined the approach of simultaneously using BIM and LC in megaprojects.Therefore,an intensive study on the application of BIM and LC in megaprojects,particularly to explore considerably effective integrated application modes of BIM and LC in megaprojects,will substantially promote the management efficiency of megaprojects.The current study describes a method that integrates owner-dominated BIM and LC that was developed in a case study.The proposed method provides a framework for all stakeholders to use BIM and LC in a megaproject dominated by the owner.The interactional relations among the owner,BIM,and LC were analyzed and positive interactions were identified.These positive interactions served as a basis for the implementation of this integrated approach in a case study and could be applied to other megaprojects.The megaproject(i.e.,airport construction project)was examined to verify the performance of the developed method.Results showed that the integration of BIM and LC dominated by the owner can improve management performance and achieve high quality standard.展开更多
Seeking high performance adsorbents for highly efficient treatment of wastewater containing organic dyes has become increasingly imperative worldwide.Herein,with a specific surface area(SSA)of 2,745.4 m^(2)·g^(−1...Seeking high performance adsorbents for highly efficient treatment of wastewater containing organic dyes has become increasingly imperative worldwide.Herein,with a specific surface area(SSA)of 2,745.4 m^(2)·g^(−1),trace N-doped porous biochar nanospheres(NPBs)are derived for the first time from affluent waste corn roots,via a hydrothermal conversion followed by a mild calcined activation by K2CO3(KC)in the presence of low virulent melamine.Melamine acts as N source and synergistic activator for significant promotion in SSA,pore volume,and surface defects.The obtained NPBs(CHC-0.5N-4KC-900)are confirmed as superior adsorbents for removal of organic dyes rhodamine B(RhB,qm=1,630.7 mg·g^(−1))and Congo red(CR,qm=1,766.2 mg·g^(−1))as well as their mixtures,within not only a low(<50 mg·L^(−1))but also a high(>50,esp.250–1500 mg·L^(−1))concentration range.The values for qm are far beyond commercially activated carbon(AC)as well as most reported biomass derived carbons,undoubtedly revealing the NPBs as great promising candidate adsorbents for disposal of real industrial wastewater.In addition,the adsorption of RhB is fitted by Langmuir,Freundlich,Temkin,and Dubinin–Radushkevich isotherm models.The kinetic analysis indicates that the adsorption before equilibrium conforms to the pseudo-second-order model,and the hydrogen bonding,electrostatic attraction,and esp.π–πinteraction have contributed to the superior adsorption performance of the NPBs.展开更多
Objective Assess whether local health facilities can adequately support the performance of general practitioners(GPs)trained by China’s national compulsory services programme(CSP).Design Prospective cohort study.Sett...Objective Assess whether local health facilities can adequately support the performance of general practitioners(GPs)trained by China’s national compulsory services programme(CSP).Design Prospective cohort study.Setting Health facilities in middle and western rural areas in China,2015–2022.Participants Cohorts of CSP graduates from 2015 to 2019 in four major medical universities.Main outcomes Job performance measured by a 12-item Job Performance Scale;productivity measured by outpatient volume per day;turnover measured by ever changing jobs within the past year.Results 91.2%,92.0%and 90.5%GPs working in township health centres reported inadequate medication,equipment and external assistance from higher level hospitals,while CSP graduates working in secondary or tertiary hospitals reported a lower rate of less than 60%.The top three tests reported as lacking were blood gases(67.7%),microbiology(61.6%)and cancer biomarkers(49.7%);the top three lacked procedures were CT scan(64.8%),MRI scan(58.1%)and ambulatory BP monitoring(55.8%);and the top three lacked drugs were drugs for cardiovascular diseases(23.3%),systematic hormonal preparations(17.7%)and traditional Chinese medicines(13.0%).Multivariable analysis showed that facility support was positively associated with job performance—adequate medication increased job performance by 2.2 points(95%CI 0.7to 3.8),and adequate external assistance increased job performance by 3.3 points(95%CI 1.8to 4.8).Facility support was also positively associated with productivity—adequate medication increased outpatients seen per day by 20%(95%CI 0.1to 0.3),and adequate equipment increased outpatients seen per day by 12%(95%CI 0.0to 0.2).Facility support did not have significant impact on turnover,but GPs who changed jobs in the past year were 1.9–2.3 times more likely to report adequate facility support.Conclusion GPs in township health centres experienced a high prevalence of shortage in facility support.The identification of a positive association between facility support and performance and productivity has implications for future research and resources deployment in primary healthcare.展开更多
Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective stu...Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective studies of epidemic outbreaks. Here, we report three confirmed patients(2015–2016) with typical symptoms of severe fever with thrombocytopenia syndrome disease(SFTS) who were farmers resident in different regions in Hubei Province. Three new SFTSV strains were isolated from the serum samples of each patient. Characterization of viral growth properties showed that there were no significant differences in virus production. All strains were completely sequenced, and phylogenetic analysis showed that unlike the other strains from Hubei province, which belonged to the SFTSV C3 genotype, one of the three strains belonged to the SFTSV C2 genotype. These results suggested that multiple SFTSV genotypes have been circulating in Hubei Province, providing insights into SFTSV evolution and improving our understanding of SFTSV prevalence in Hubei Province.展开更多
Heavy metal pollution affects soil ecological function.Biochar and compost can effectively remediate heavy metals and increase soil nutrients.The effects and mechanisms of biochar and compost amendments on soil nitrog...Heavy metal pollution affects soil ecological function.Biochar and compost can effectively remediate heavy metals and increase soil nutrients.The effects and mechanisms of biochar and compost amendments on soil nitrogen cycle function in heavy-metal contaminated soils are not fully understood.This study examined how biochar,compost,and their integrated use affected ammonia-oxidizing microorganisms in heavy metal polluted soil.Quantitative PCR was used to determine the abundance of ammonia-oxidizing archaea(AOA)and bacteria(AOB).Ammonia monooxygenase(AMO)activity was evaluated by the enzymelinked immunosorbent assay.Results showed that compost rather than biochar improved nitrogen conversion in soil.Biochar,compost,or their integrated application significantly reduced the effective Zn and Cd speciation.Adding compost obviously increased As and Cu effective speciation,bacterial 16 S rRNA abundance,and AMO activity.AOB,stimulated by compost addition,was significantly more abundant than AOA throughout remediation.Correlation analysis showed that AOB abundance positively correlated with NO_(3)^(-)-N(r=0.830,P<0.01),and that AMO activity had significant correlation with EC(r=-0.908,P<0.01)and water-soluble carbon(r=-0.868,P<0.01).Those seem to be the most vital factors affecting AOB community and their function in heavy metal-polluted soil remediated by biochar and compost.展开更多
Oxidative post-translational modifications of specific chloroplast proteins contribute to the initiation of retrograde signaling.The Arabidopsis thaliana EXECUTER1(EX1)protein,a chloroplast-localized singlet oxygen(^(...Oxidative post-translational modifications of specific chloroplast proteins contribute to the initiation of retrograde signaling.The Arabidopsis thaliana EXECUTER1(EX1)protein,a chloroplast-localized singlet oxygen(^(1)O_(2))sensor,undergoes tryptophan(Trp)643 oxidation by^(1)O_(2),a chloroplast-derived and light-dependent reactive oxygen species.The indole side chain of Trp is vulnerable to^(1)O_(2),leading to the generation of oxidized Trp variants and priming EX1 for degradation by a membrane-bound FtsH protease.The perception of^(1)O_(2)via Trp643 oxidation and subsequent EX1 proteolysis facilitate chloroplast-to-nucleus retrograde signaling.In this study,we discovered that the EX1-like protein EX2 also undergoes^(1)O_(2)-dependent Trp530 oxidation and FtsH-dependent turnover,which attenuates^(1)O_(2)signaling by decelerating EX1-Trp643 oxidation and subsequent EX1 degradation.Consistent with this finding,the loss of EX2 function reinforces EX1-dependent retrograde signaling by accelerating EX1-Trp643 oxidation and subsequent EX1 proteolysis,whereas overexpression of EX2 produces molecular phenotypes opposite to those observed in the loss-of-function mutants of EX2.Intriguingly,phylogenetic analysis suggests that EX2 may have emerged evolutionarily to attenuate the sensitivity of EX1 toward^(1)O_(2).Collectively,these results suggest that EX2 functions as a negative regulator of the EX1 signalosome through its own^(1)O_(2)-dependent oxidation,providing a new mechanistic insight into the regulation of EX1-mediated^(1)O_(2)signaling.展开更多
基金supported by the National Natural Science Foundation of China(numbers:81774416 and 81473764)。
文摘Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.
基金This work was financially supported by the National Natural Science Foundation of China(82273794 to Yue Chen and 82073879 to Jing Li.)the Natural Science Foundation of Tianjin(21JCYBJC00190 to Jing Li and 20JCYBJC01000 to Yue Chen)the Postdoctoral Science Foundation of China(2021M701791).
文摘Aberrant changes in the gut microbiota are implicated in many diseases,including inflammatory bowel disease(IBD).Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity,indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD.Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies,novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed.Herein,we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone(an enantiomer)as a potent agent against experimental colitis that acts by modulating the gut microbiota.5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids(SCFAs);thus,it regulates the intestinal immune system by reducing proinflammatory immune cell numbers,and maintains intestinal mucosal integrity by modulating tight junctions(TJs).Moreover,5S-heudelotinone(2)ameliorates colitis-associated colorectal cancer(CAC)in an azoxymethane(AOM)/dextran sulfate sodium(DSS)-induced in situ carcinoma model.Together,these findings reveal the potential of a novel natural product,namely,5S-heudelotinone,to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.
基金This work was supported by the National Key Research and Development Program of China(2018YFA0801104 and 2021YFA1301604)the National Natural Science Foundation of China(82372721,31630093,and 82394443)Independent Research Program of the State Key Laboratory of Proteomics(SKLP-K202004).
文摘Endothelial cells(ECs)form a single cell layer that lines the inner surface of all blood and lymphatic vessels,acting as the barrier between vessels and underlying tissues.ECs are not only responsible for the flow of substances and fluid into and out of tissues but are also involved in many processes,such as coagulation,fibrinolysis,and regulation of vascular tone and inflammation.
基金supported by the Shandong Provincial Nature Science Foundation(ZR2020QH240)the National Nature Science Foundation of China(NSFC82002719)the China Postdoctoral Science Foundation(2022 M711977).
文摘Objectives:This study aims to not only investigate the prevalence of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer but also identify the contributing factors.Materials and methods:A total of 245 elderly patients diagnosed with prostate cancer and undergoing radical prostatectomy at a tertiary care general hospital in Jinan were included in this study.To assess the patients,several questionnaires were used.These included the General Situation Questionnaire,General Alienation Scale,Social Impact Scale,Modified Memorial Anxiety Scale for Prostate Cancer,and Perceived Social Support Scale.Pearson correlation analysis was conducted to examine the relationships between variables,whereas multiple linear regression was used to identify the factors influencing social alienation among patients who underwent radical prostatectomy.Results:Patients who underwent radical prostatectomy had a mean total score of 44.13±7.24 on the Social Alienation Scale.The results of the Pearson correlation analysis indicated that social alienation showed an inverse association with social support(r=−0.627,p<0.05)and positive associations with age,disease stigma,and anxiety(r=0.325,0.575,0.421,all p’s<0.01)among patients who underwent radical prostatectomy.The findings frommultiple linear regression analysis demonstrated that educational level,age,urinary incontinence,disease stigma,anxiety,and social support significantly influenced social alienation among elderly patients who underwent radical prostatectomy(p<0.05).Conclusions:Elderly patients who undergo radical prostatectomy often experience social alienation.This study found that social alienation was associated with factors such as educational level,age,urinary incontinence,social support,anxiety,and disease stigma.Consequently,healthcare providers should actively monitor the degree of social alienation in elderly patients after radical prostatectomy and provide suitable psychological care to facilitate positive social reintegration and alleviate their feelings of social alienation.
基金This work was granted by the National Natural Science Foundation of China(81072896 and 81704198).
文摘Objective:To analyze the impact of meteorological factors on the incidence of influenza based on the Yunqi theory in Beijing area,and to establish an effective forecast modelMethods:Monthly data on the incidence of influenza from 1970 to 2004 and daily data on the meteorological factors (including daily averages of temperature,wind speed,relative humidity,vapor pressure,and daily total precipitation) from 1966 to 2004 were collected and processed under the traditional Chinese medicine (TCM) theory of six qi.A back-propagation artificial neural network was then performed to analyze the data.Results:The highest incidence of influenza occurs in the sixth qi (the period of December and January),which is characterized by dryness and coldness.Altogether six models were successfully established.Climatic data used were of the same year,one year prior,two years prior,and three years prior to the influenza data respectively.The last two models involve climatic data of the previous three years plus the current year and of the past four years plus the current year.Finally,we determined the fifth model has the highest forecast accuracy (49%).Conclusions:Meteorological factors can exert an influence on the incidence of influenza,which corresponds to TCM theory that 'the pestilence occurred three years after the abnormal climatic changes'.This study may generate interest among the public health community and other TCM theories can be applied so that public health measures can be taken to prevent and control influenza,particularly during the winter months.
基金supported by the National Key R&D Program of China (No.2018YFA0704703)National Natural Science Foundation of China (Nos.61972215,61972073,and 62172238)Natural Science Foundation of Tianjin (No.20JCZDJC00640).
文摘In cloud storage,client-side deduplication is widely used to reduce storage and communication costs.In client-side deduplication,if the cloud server detects that the user’s outsourced data have been stored,then clients will not need to reupload the data.However,the information on whether data need to be uploaded can be used as a side-channel,which can consequently be exploited by adversaries to compromise data privacy.In this paper,we propose a new threat model against side-channel attacks.Different from existing schemes,the adversary could learn the approximate ratio of stored chunks to unstored chunks in outsourced files,and this ratio will affect the probability that the adversary compromises the data privacy through side-channel attacks.Under this threat model,we design two defense schemes to minimize privacy leakage,both of which design interaction protocols between clients and the server during deduplication checks to reduce the probability that the adversary compromises data privacy.We analyze the security of our schemes,and evaluate their performances based on a real-world dataset.Compared with existing schemes,our schemes can better mitigate data privacy leakage and have a slightly lower communication cost.
基金supported by the National Natural Science Foundation of China (No.61972073)the Key Program of Natural Science Foundation of Hebei Province of China (No.F2019201290)the Natural Science Foundation of Hebei Province of China (No.F2018201153).
文摘While users enjoy the convenience of data outsourcing in the cloud,they also face the risks of data modification and private information leakage.Searchable encryption technology can perform keyword searches over encrypted data while protecting their privacy and guaranteeing the integrity of the data by verifying the search results.However,some associated problems are still encountered,such as the low efficiency of verification and uncontrollable query results.Accordingly,this paper proposes a Privacy-Preserving Searchable Encryption(PPSE)scheme based on public and private blockchains.First,we store an encrypted index in a private blockchain while outsourcing corresponding encrypted documents to a public blockchain.The encrypted documents are located through the encrypted index.This method can reduce the storage overhead on the blockchains,and improve the efficiency of transaction execution and the security of stored data.Moreover,we adopt a smart contract to introduce a secondary verification access control mechanism and restrict data users’access to the private blockchain through authorization for the purpose of guaranteeing data privacy and the correctness of access control verification.Finally,the security analysis and experimental results indicate that compared with existing schemes,the proposed scheme can not only improve the security of encrypted data but also guarantee the efficiency of the query.
文摘Carbon cycle is one of the focuses of climate change, river carbon is an important part, while dissolved inorganic carbon (DIC) has a high proportion of river carbon flux. In this study, we did the research on the Lancang River, an important international river in the southwest of China. Water samples were obtained from 16 sections of the middle and lower reaches of the Lancang River in 2016 (11 months), then we monitored some water quality indicators and DIC content, finally analyzed the temporal-spatial distribution characteristics of DIC and the relationship between DIC content and water environment factors. The results showed that: (1) DIC contents in the middle and lower reaches of the Lancang River varied from 1.1840 mmol/L to 3.1440 mmol/L, with a mean value of about 2.2155 mmol/L. (2) At a time scale, DIC contents of dry season (spring, autumn and winter) were higher than rainy season (summer). At a space scale, DIC contents of the middle and lower reaches of the Lancang River gradually decreased from north to south, and each reservoir had the same characteristics, that is, DIC contents at upstream of the dam was lower than those at downstream of the dam. Compared to other rivers with cascade dams around the world, DIC contents within studied river were at similar level. And the reservoir’s effect of the Lancang River were not obvious, however, DIC contents in the water sampled upstream the dams had a slight stratification. (3) Water temperature, conductivity, turbidity were important factors affecting DIC content of water, and the effect of oxidation and reduction potential (ORP) and pH on DIC was relatively small.
基金Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province(20230005)Qingdao Demonstration and Guidance Project of Science and Technology to Benefit the People(21-1-4-sf-17-nsh)+3 种基金National Natural Science Foundation of China(42107419,51878363,42177028)Natural Science Foundation of Shandong Province(ZR2019YQ18)Science and Technology Support Plan for Youth Innovation of Colleges in Shandong Province(DC2000000961)National College Students Innovation and Entrepreneurship Training Program of China(S20211106514).
文摘Immobilized microbial technology has been widely used in wastewater treatment,but it has been used less frequently for soil remediation,particularly in sites that are co-contaminated with organic compounds and heavy metals.In addition,there is limited knowledge on the efficiency of remediation and microbial preferences to colonize the immobilized carriers.In this study,biochar immobilized with Sphingobium abikonense was introduced to remediate soils that were co-contaminated with phenanthrene(PHE)and copper(Cu),and the mechanisms of microbial assemblage were investigated.The immobilized microbial biochar maintained a degradation rate of more than 96%in both the first(0-6 d)and second(6-12 d)contamination periods.The addition of biochar increased the proportion of Cu bound to organic matter,and Fe-Mn oxide bound Cu in the soil.In addition,both Cu and PHE could be adsorbed into biochar pellets in the presence or absence of immobilized S.abikonense.The presence of biochar significantly increased the abundance of bacteria,such as Luteibacter,Bordetella and Dyella,that could degrade organic matter and tolerate heavy metals.Notably,the biochar could specifically select host microbes from the soil for colonization,while the presence of S.abikonense affected this preference.The autonomous selection facilitates the degradation of PHE and/or the immobilization of Cu in the soil.These results provide a green approach to efficiently and sustainably remediate soil co-contaminated with PHE and Cu and highlight the importance of microbial preference colonized in immobilized carriers.
基金Beijing Natural Science Foundation(L222027)Beijing High Level Public Health Technical Talents Training Plan(2022-1-005,Key Discipline Member-02-44).
文摘Summary What is already known about this topic?In December 2022,China revised its epidemic prevention and control strategy,leading to an increase in coronavirus disease 2019(COVID-19)cases and a peak in medical consultations.Government departments implemented relevant policies to coordinate and allocate medical resources throughout China.However,there is a scarcity of research on the status of medical consultations and the factors influencing them.
基金funded by the grants from the National Key R&D Program of China(Grant No.2019YFC1316204)the National Natural Science Foundation of China(Grant Nos.81974249,31770983,82070136,and 82104488)the Hubei Provincial Natural Science Foundation of China(Grant No.2020BHB016).
文摘Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administration significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.
基金This study was supported by the Key Research Projects in Colleges and Universities(15A560021)Key Research Projects of Henan Science and Technology Department(182107000007).
文摘The integration of building information modeling(BIM)and lean construction(LC)provides a solution for the management of megaprojects.Previous studies have generally focused on the theoretical or empirical adoption of BIM and LC.Moreover,only a few studies have examined the approach of simultaneously using BIM and LC in megaprojects.Therefore,an intensive study on the application of BIM and LC in megaprojects,particularly to explore considerably effective integrated application modes of BIM and LC in megaprojects,will substantially promote the management efficiency of megaprojects.The current study describes a method that integrates owner-dominated BIM and LC that was developed in a case study.The proposed method provides a framework for all stakeholders to use BIM and LC in a megaproject dominated by the owner.The interactional relations among the owner,BIM,and LC were analyzed and positive interactions were identified.These positive interactions served as a basis for the implementation of this integrated approach in a case study and could be applied to other megaprojects.The megaproject(i.e.,airport construction project)was examined to verify the performance of the developed method.Results showed that the integration of BIM and LC dominated by the owner can improve management performance and achieve high quality standard.
基金supported by the State Key Laboratory of Chemical Engineering,China(No.SKL-ChE-21A02)State Key Laboratory of Organic-Inorganic Composites,China(No.oic-202101009)+2 种基金the Natural Science Foundation of Shandong Province,China(No.ZR2022MB075)the National Natural Science Foundation of China(No.22075304)Beijing Natural Science Foundation,China(No.3222050).
文摘Seeking high performance adsorbents for highly efficient treatment of wastewater containing organic dyes has become increasingly imperative worldwide.Herein,with a specific surface area(SSA)of 2,745.4 m^(2)·g^(−1),trace N-doped porous biochar nanospheres(NPBs)are derived for the first time from affluent waste corn roots,via a hydrothermal conversion followed by a mild calcined activation by K2CO3(KC)in the presence of low virulent melamine.Melamine acts as N source and synergistic activator for significant promotion in SSA,pore volume,and surface defects.The obtained NPBs(CHC-0.5N-4KC-900)are confirmed as superior adsorbents for removal of organic dyes rhodamine B(RhB,qm=1,630.7 mg·g^(−1))and Congo red(CR,qm=1,766.2 mg·g^(−1))as well as their mixtures,within not only a low(<50 mg·L^(−1))but also a high(>50,esp.250–1500 mg·L^(−1))concentration range.The values for qm are far beyond commercially activated carbon(AC)as well as most reported biomass derived carbons,undoubtedly revealing the NPBs as great promising candidate adsorbents for disposal of real industrial wastewater.In addition,the adsorption of RhB is fitted by Langmuir,Freundlich,Temkin,and Dubinin–Radushkevich isotherm models.The kinetic analysis indicates that the adsorption before equilibrium conforms to the pseudo-second-order model,and the hydrogen bonding,electrostatic attraction,and esp.π–πinteraction have contributed to the superior adsorption performance of the NPBs.
基金This study involves human participants and was approved by Institutional Review Board of Peking University Health Science Center(PU IRB)(IRB00001052-15027).
文摘Objective Assess whether local health facilities can adequately support the performance of general practitioners(GPs)trained by China’s national compulsory services programme(CSP).Design Prospective cohort study.Setting Health facilities in middle and western rural areas in China,2015–2022.Participants Cohorts of CSP graduates from 2015 to 2019 in four major medical universities.Main outcomes Job performance measured by a 12-item Job Performance Scale;productivity measured by outpatient volume per day;turnover measured by ever changing jobs within the past year.Results 91.2%,92.0%and 90.5%GPs working in township health centres reported inadequate medication,equipment and external assistance from higher level hospitals,while CSP graduates working in secondary or tertiary hospitals reported a lower rate of less than 60%.The top three tests reported as lacking were blood gases(67.7%),microbiology(61.6%)and cancer biomarkers(49.7%);the top three lacked procedures were CT scan(64.8%),MRI scan(58.1%)and ambulatory BP monitoring(55.8%);and the top three lacked drugs were drugs for cardiovascular diseases(23.3%),systematic hormonal preparations(17.7%)and traditional Chinese medicines(13.0%).Multivariable analysis showed that facility support was positively associated with job performance—adequate medication increased job performance by 2.2 points(95%CI 0.7to 3.8),and adequate external assistance increased job performance by 3.3 points(95%CI 1.8to 4.8).Facility support was also positively associated with productivity—adequate medication increased outpatients seen per day by 20%(95%CI 0.1to 0.3),and adequate equipment increased outpatients seen per day by 12%(95%CI 0.0to 0.2).Facility support did not have significant impact on turnover,but GPs who changed jobs in the past year were 1.9–2.3 times more likely to report adequate facility support.Conclusion GPs in township health centres experienced a high prevalence of shortage in facility support.The identification of a positive association between facility support and performance and productivity has implications for future research and resources deployment in primary healthcare.
基金supported by the Science and Technology Basic Work Program (2013FY113500)the National Key Research and Development Program (2016YFE 0113500) from the Ministry of Science and Technology of Chinathe European Union’s Horizon 2020 EVAg project (No 653316)
文摘Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective studies of epidemic outbreaks. Here, we report three confirmed patients(2015–2016) with typical symptoms of severe fever with thrombocytopenia syndrome disease(SFTS) who were farmers resident in different regions in Hubei Province. Three new SFTSV strains were isolated from the serum samples of each patient. Characterization of viral growth properties showed that there were no significant differences in virus production. All strains were completely sequenced, and phylogenetic analysis showed that unlike the other strains from Hubei province, which belonged to the SFTSV C3 genotype, one of the three strains belonged to the SFTSV C2 genotype. These results suggested that multiple SFTSV genotypes have been circulating in Hubei Province, providing insights into SFTSV evolution and improving our understanding of SFTSV prevalence in Hubei Province.
基金supported by the Hunan Provincial Key Research and Development Project(Nos.2019WK2031 and 2017SK2351)the National Natural Science Foundation of China(No.51408219)+1 种基金the Natural Science Foundation of Hu-nan Province(No.2020JJ5259)the Outstanding Youth Fund Project of the Hunan Education Department(No.18B094)。
文摘Heavy metal pollution affects soil ecological function.Biochar and compost can effectively remediate heavy metals and increase soil nutrients.The effects and mechanisms of biochar and compost amendments on soil nitrogen cycle function in heavy-metal contaminated soils are not fully understood.This study examined how biochar,compost,and their integrated use affected ammonia-oxidizing microorganisms in heavy metal polluted soil.Quantitative PCR was used to determine the abundance of ammonia-oxidizing archaea(AOA)and bacteria(AOB).Ammonia monooxygenase(AMO)activity was evaluated by the enzymelinked immunosorbent assay.Results showed that compost rather than biochar improved nitrogen conversion in soil.Biochar,compost,or their integrated application significantly reduced the effective Zn and Cd speciation.Adding compost obviously increased As and Cu effective speciation,bacterial 16 S rRNA abundance,and AMO activity.AOB,stimulated by compost addition,was significantly more abundant than AOA throughout remediation.Correlation analysis showed that AOB abundance positively correlated with NO_(3)^(-)-N(r=0.830,P<0.01),and that AMO activity had significant correlation with EC(r=-0.908,P<0.01)and water-soluble carbon(r=-0.868,P<0.01).Those seem to be the most vital factors affecting AOB community and their function in heavy metal-polluted soil remediated by biochar and compost.
基金This research was supported by the Strategic Priority Research Program from the Chinese Academy of Sciences(grant no.XDB27040102)the 100-Talent Program of the Chinese Academy of Sciences and the National Natural Science Foundation of China(NSFC)(grant no.31871397)to C.K.Support from a President's International Fellowship Initiative(PIFI)postdoctoral fellowship from the Chinese Academy of Sciences(no.2019PB0066)to V.D.is also acknowledged.
文摘Oxidative post-translational modifications of specific chloroplast proteins contribute to the initiation of retrograde signaling.The Arabidopsis thaliana EXECUTER1(EX1)protein,a chloroplast-localized singlet oxygen(^(1)O_(2))sensor,undergoes tryptophan(Trp)643 oxidation by^(1)O_(2),a chloroplast-derived and light-dependent reactive oxygen species.The indole side chain of Trp is vulnerable to^(1)O_(2),leading to the generation of oxidized Trp variants and priming EX1 for degradation by a membrane-bound FtsH protease.The perception of^(1)O_(2)via Trp643 oxidation and subsequent EX1 proteolysis facilitate chloroplast-to-nucleus retrograde signaling.In this study,we discovered that the EX1-like protein EX2 also undergoes^(1)O_(2)-dependent Trp530 oxidation and FtsH-dependent turnover,which attenuates^(1)O_(2)signaling by decelerating EX1-Trp643 oxidation and subsequent EX1 degradation.Consistent with this finding,the loss of EX2 function reinforces EX1-dependent retrograde signaling by accelerating EX1-Trp643 oxidation and subsequent EX1 proteolysis,whereas overexpression of EX2 produces molecular phenotypes opposite to those observed in the loss-of-function mutants of EX2.Intriguingly,phylogenetic analysis suggests that EX2 may have emerged evolutionarily to attenuate the sensitivity of EX1 toward^(1)O_(2).Collectively,these results suggest that EX2 functions as a negative regulator of the EX1 signalosome through its own^(1)O_(2)-dependent oxidation,providing a new mechanistic insight into the regulation of EX1-mediated^(1)O_(2)signaling.
