In dentistry, panoramic X-ray images are extensively used by dentists for tooth structure analysis and disease diagnosis. However, the manual analysis of these images is time-consuming and prone to misdiagnosis or ove...In dentistry, panoramic X-ray images are extensively used by dentists for tooth structure analysis and disease diagnosis. However, the manual analysis of these images is time-consuming and prone to misdiagnosis or overlooked. While deep learning techniques have been employed to segment teeth in panoramic X-ray images, accurate segmentation of individual teeth remains an underexplored area. In this study, we propose an end-to-end deep learning method that effectively addresses this challenge by employing an improved combinatorial loss function to separate the boundaries of adjacent teeth, enabling precise segmentation of individual teeth in panoramic X-ray images. We validate the feasibility of our approach using a challenging dataset. By training our segmentation network on 115 panoramic X-ray images, we achieve an intersection over union (IoU) of 86.56% for tooth segmentation and an accuracy of 65.52% in tooth counting on 87 test set images. Experimental results demonstrate the significant improvement of our proposed method in single tooth segmentation compared to existing methods.展开更多
Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classica...Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classically activated macrophage(M1)polarization.In this study,we established THP-1-derived testing state macrophages(M0),M1 macrophages,and alternately activated macrophages(M2).Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages.Flow cytometry was used to detect phenotypic proteins(CD11b,CD38,CD80).We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048.Flow cytometry,western blot,and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response,while over-expression of lnc_000048 led to the opposite effect.Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization.Moreover,catRAPID prediction,RNA-pull down,and mass spectrometry were used to identify and screen the protein kinase RNA-activated(PKR),then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR.Immunofluorescence(IF)-RNA fluorescence in situ hybridization(FISH)double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage.We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation,leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression.Taken together,these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.展开更多
Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shel...Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.展开更多
Hydrogen energy has emerged as a pivotal solution to address the global energy crisis and pave the way for a cleaner,low-carbon,secure,and efficient modern energy system.A key imperative in the utilization of hydrogen...Hydrogen energy has emerged as a pivotal solution to address the global energy crisis and pave the way for a cleaner,low-carbon,secure,and efficient modern energy system.A key imperative in the utilization of hydrogen energy lies in the development of high-performance hydrogen storage materials.Magnesium-based hydrogen storage materials exhibit remarkable advantages,including high hydrogen storage density,cost-effectiveness,and abundant magnesium resources,making them highly promising for the hydrogen energy sector.Nonetheless,practical applications of magnesium hydride for hydrogen storage face significant challenges,primarily due to their slow kinetics and stable thermodynamic properties.Herein,we briefly summarize the thermodynamic and kinetic properties of MgH2,encompassing strategies such as alloying,nanoscaling,catalyst doping,and composite system construction to enhance its hydrogen storage performance.Notably,nanoscaling and catalyst doping have emerged as more effective modification strategies.The discussion focuses on the thermodynamic changes induced by nanoscaling and the kinetic enhancements resulting from catalyst doping.Particular emphasis lies in the synergistic improvement strategy of incorporating nanocatalysts with confinement materials,and we revisit typical works on the multi-strategy optimization of MgH2.In conclusion,we conduct an analysis of outstanding challenges and issues,followed by presenting future research and development prospects for MgH2 as hydrogen storage materials.展开更多
The oil production of the multi-fractured horizontal wells(MFHWs) declines quickly in unconventional oil reservoirs due to the fast depletion of natural energy. Gas injection has been acknowledged as an effective meth...The oil production of the multi-fractured horizontal wells(MFHWs) declines quickly in unconventional oil reservoirs due to the fast depletion of natural energy. Gas injection has been acknowledged as an effective method to improve oil recovery factor from unconventional oil reservoirs. Hydrocarbon gas huff-n-puff becomes preferable when the CO_(2) source is limited. However, the impact of complex fracture networks and well interference on the EOR performance of multiple MFHWs is still unclear. The optimal gas huff-n-puff parameters are significant for enhancing oil recovery. This work aims to optimize the hydrocarbon gas injection and production parameters for multiple MFHWs with complex fracture networks in unconventional oil reservoirs. Firstly, the numerical model based on unstructured grids is developed to characterize the complex fracture networks and capture the dynamic fracture features.Secondly, the PVT phase behavior simulation was carried out to provide the fluid model for numerical simulation. Thirdly, the optimal parameters for hydrocarbon gas huff-n-puff were obtained. Finally, the dominant factors of hydrocarbon gas huff-n-puff under complex fracture networks are obtained by fuzzy mathematical method. Results reveal that the current pressure of hydrocarbon gas injection can achieve miscible displacement. The optimal injection and production parameters are obtained by single-factor analysis to analyze the effect of individual parameter. Gas injection time is the dominant factor of hydrocarbon gas huff-n-puff in unconventional oil reservoirs with complex fracture networks. This work can offer engineers guidance for hydrocarbon gas huff-n-puff of multiple MFHWs considering the complex fracture networks.展开更多
The clinical application of magnesium(Mg)and its alloys for bone fractures has been well supported by in vitro and in vivo trials.However,there were studies indicating negative effects of high dose Mg intake and susta...The clinical application of magnesium(Mg)and its alloys for bone fractures has been well supported by in vitro and in vivo trials.However,there were studies indicating negative effects of high dose Mg intake and sustained local release of Mg ions on bone metabolism or repair,which should not be ignored when developing Mg-based implants.Thus,it remains necessary to assess the biological effects of Mg implants in animal models relevant to clinical treatment modalities.The primary purpose of this study was to validate the beneficial effects of intramedullary Mg implants on the healing outcome of femoral fractures in a modified rat model.In addition,the mineralization parameters at multiple anatomical sites were evaluated,to investigate their association with healing outcome and potential clinical applications.Compared to the control group without Mg implantation,postoperative imaging at week 12 demonstrated better healing outcomes in the Mg group,with more stable unions in 3D analysis and high-mineralized bridging in 2D evaluation.The bone tissue mineral density(TMD)was higher in the Mg group at the non-operated femur and lumbar vertebra,while no differences between groups were identified regarding the bone tissue volume(TV),TMD and bone mineral content(BMC)in humerus.In the surgical femur,the Mg group presented higher TMD,but lower TV and BMC in the distal metaphyseal region,as well as reduced BMC at the osteotomy site.Principal component analysis(PCA)-based machine learning revealed that by selecting clinically relevant parameters,radiological markers could be constructed for differentiation of healing outcomes,with better performance than 2D scoring.The study provides insights and preclinical evidence for the rational investigation of bioactive materials,the identification of potential adverse effects,and the promotion of diagnostic capabilities for fracture healing.展开更多
Solid polymer composite electrolytes possess the benefits of superior compatibility with electrodes and good thermal characteristics for more secure energy storage equipment.Herein,a new gel polymer electrolyte(GPE)co...Solid polymer composite electrolytes possess the benefits of superior compatibility with electrodes and good thermal characteristics for more secure energy storage equipment.Herein,a new gel polymer electrolyte(GPE)containing NH_(2)-MIL-53(Al),[PP_(13)][TFSI],LiTFSI,and PVDF-HFP was prepared using a simple method of solution casting.The effects of encapsulating different ratios of ionic liquid([PP_(13)][TFSI])into the micropores of functionalized metal-organic frameworks(NH_(2)-MIL-53(Al))on the electrochemical properties were compared.XRD,SEM,nitrogen adsorption-desorption isotherms,and electrochemical measurements were conducted.This GPE demonstrates a superior ionic conductivity of 8.08×10^(-4)S·cm^(-1)at 60℃and can sustain a discharge specific capacity of 156.6 mA·h·g^(-1)at 0.2 C for over 100 cycles.This work might offer a potential approach to alleviate the solid-solid contact with the solid-state electrolyte and electrodes and broaden a new window for the creation of all-solid-state batteries.展开更多
The flying foxes optimization(FFO)algorithm,as a newly introduced metaheuristic algorithm,is inspired by the survival tactics of flying foxes in heat wave environments.FFO preferentially selects the best-performing in...The flying foxes optimization(FFO)algorithm,as a newly introduced metaheuristic algorithm,is inspired by the survival tactics of flying foxes in heat wave environments.FFO preferentially selects the best-performing individuals.This tendency will cause the newly generated solution to remain closely tied to the candidate optimal in the search area.To address this issue,the paper introduces an opposition-based learning-based search mechanism for FFO algorithm(IFFO).Firstly,this paper introduces niching techniques to improve the survival list method,which not only focuses on the adaptability of individuals but also considers the population’s crowding degree to enhance the global search capability.Secondly,an initialization strategy of opposition-based learning is used to perturb the initial population and elevate its quality.Finally,to verify the superiority of the improved search mechanism,IFFO,FFO and the cutting-edge metaheuristic algorithms are compared and analyzed using a set of test functions.The results prove that compared with other algorithms,IFFO is characterized by its rapid convergence,precise results and robust stability.展开更多
Historically,the rapid degradation and massive gas release from magnesium(Mg)implants resulted in severe emphysema and mechanical failure.With the advent of new alloys and surface treatment methods,optimized Mg implan...Historically,the rapid degradation and massive gas release from magnesium(Mg)implants resulted in severe emphysema and mechanical failure.With the advent of new alloys and surface treatment methods,optimized Mg implants have re-entered clinics since last decade with reliable performance.However,the optimization aims at slowing down the degradation process,rather than exemption of the gas release.This study involved a systematic evaluation of current preclinical and clinical evidence,regarding the physical signs,symptoms,radiological features,pathological findings and complications potentially associated with peri±implant gas accumulation(PIGA)after musculoskeletal Mg implantation.The literature search identified 196 potentially relevant publications,and 51 papers were enrolled for further analysis,including 22 preclinical tests and 29 clinical studies published from 2005 to 2023.Various Mg-based materials have been evaluated in animal research,and the application of pure Mg and Mg alloys have been reported in clinical follow-ups involving multiple anatomical sites and musculoskeletal disorders.Soft tissue and intraosseous PIGA are common in both animal tests and clinical follow-ups,and potentially associated with certain adverse events.Radiological examinations especially micro-CT and clinical CT scans provide valuable information for quantitative and longitudinal analysis.While according to simulation tests involving Mg implantation and chemical processing,tissue fixation could lead to an increase in the volume of gas cavity,thus the results obtained from ex vivo imaging or histopathological evaluations should be interpreted with caution.There still lacks standardized procedures or consensus for both preclinical and clinical evaluation of PIGA.However,by providing focused insights into the topic,this evidence-based study will facilitate future animal tests and clinical evaluations,and support developing biocompatible Mg implants for the treatment of musculoskeletal disorders.展开更多
Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genet...Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.展开更多
BACKGROUND Gastric cancer is a common malignant tumor of the digestive system worldwide,and its early diagnosis is crucial to improve the survival rate of patients.Indocyanine green fluorescence imaging(ICG-FI),as a n...BACKGROUND Gastric cancer is a common malignant tumor of the digestive system worldwide,and its early diagnosis is crucial to improve the survival rate of patients.Indocyanine green fluorescence imaging(ICG-FI),as a new imaging technology,has shown potential application prospects in oncology surgery.The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice.AIM To assess the diagnostic efficacy of optical imaging in conjunction with indocya-nine green(ICG)-guided sentinel lymph node(SLN)biopsy for gastric cancer.METHODS Electronic databases such as PubMed,Embase,Medline,Web of Science,and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy.Stata 12.0 software was used for analysis by combining the"bivariable mixed effect model"with the"midas"command.The true positive value,false positive value,false negative value,true negative value,and other information from the included literature were extracted.A literature quality assessment map was drawn to describe the overall quality of the included literature.A forest plot was used for heterogeneity analysis,and P<0.01 was considered to indicate statistical significance.A funnel plot was used to assess publication bias,and P<0.1 was considered to indicate statistical significance.The summary receiver operating characteristic(SROC)curve was used to calculate the area under the curve(AUC)to determine the diagnostic accuracy.If there was interstudy heterogeneity(I2>50%),meta-regression analysis and subgroup analysis were performed.analysis were performed.RESULTS Optical imaging involves two methods:Near-infrared(NIR)imaging and fluorescence imaging.A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis.The positive likelihood ratio was 30.39(95%CI:0.92-1.00),the sensitivity was 0.95(95%CI:0.82-0.99),and the specificity was 1.00(95%CI:0.92-1.00).The negative likelihood ratio was 0.05(95%CI:0.01-0.20),the diagnostic odds ratio was 225.54(95%CI:88.81-572.77),and the SROC AUC was 1.00(95%CI:The crucial values were sensitivity=0.95(95%CI:0.82-0.99)and specificity=1.00(95%CI:0.92-1.00).The Deeks method revealed that the"diagnostic odds ratio"funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical(P=0.01),suggesting significant publication bias.Further meta-subgroup analysis revealed that,compared with fluorescence imaging,NIR imaging had greater sensitivity(0.98 vs 0.73).Compared with optical imaging immediately after ICG injection,optical imaging after 20 minutes obtained greater sensitivity(0.98 vs 0.70).Compared with that of patients with an average SLN detection number<4,the sensitivity of patients with a SLN detection number≥4 was greater(0.96 vs 0.68).Compared with hematoxylin-eosin(HE)staining,immunohistochemical(+HE)staining showed greater sensitivity(0.99 vs 0.84).Compared with subserous injection of ICG,submucosal injection achieved greater sensitivity(0.98 vs 0.40).Compared with 5 g/L ICG,0.5 and 0.05 g/L ICG had greater sensitivity(0.98 vs 0.83),and cT1 stage had greater sensitivity(0.96 vs 0.72)than cT2 to cT3 clinical stage.Compared with that of patients≤26,the sensitivity of patients>26 was greater(0.96 vs 0.65).Compared with the literature published before 2010,the sensitivity of the literature published after 2010 was greater(0.97 vs 0.81),and the differences were statistically significant(all P<0.05).CONCLUSION For the diagnosis of stomach cancer,optical imaging in conjunction with ICG-guided SLN biopsy is a therapeut-ically viable approach,especially for early gastric cancer.The concentration of ICG used in the SLN biopsy of gastric cancer may be too high.Moreover,NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.展开更多
[Objectives]This study was conducted to establish a rapid quantitative method for detecting antibody against Peste des Petits Ruminants Virus(PPR V)in sheep serum.[Methods]Soluble N protein and NH fusion protein were ...[Objectives]This study was conducted to establish a rapid quantitative method for detecting antibody against Peste des Petits Ruminants Virus(PPR V)in sheep serum.[Methods]Soluble N protein and NH fusion protein were obtained in Escherichia coli prokaryotic expression system by optimizing codons and expression conditions of E.coli.Furthermore,based on the purified soluble N protein and NH fusion protein,a high-sensitivity fluorescence immunoassay kit for detecting the antibody against PPR V was established.[Results]The method could quickly and quantitatively detect PPR V antibody in sheep serum,with high sensitivity and specificity,without any cross reaction to other related sheep pathogens.The intra-batch and inter-batch coefficients of variation were less than 10%and 15%,respectively,and the method had good repeatability.Through detection on 292 clinical serum samples,it was compared with the French IDVET competitive ELISA kit,and the coincidence rate of the two methods reached 93.84%.Compared with the serum neutralization test,the detected titer value of the high-sensitivity rapid fluorescence quantitative detection method was basically consistent with the tilter value obtained by the neutralization test on the standard positive serum(provided by the WOAH Brucellosis Reference Laboratory of France).[Conclusions]This method can realize rapid quantitative detection of PPR V antibody on site,and has high practical value and popularization value.展开更多
[Objectives]This study was conducted to explore rapid and large-scale screening and detection of peste des petits ruminants(PPR),so as to provide important technical means for prevention,control and purification of PP...[Objectives]This study was conducted to explore rapid and large-scale screening and detection of peste des petits ruminants(PPR),so as to provide important technical means for prevention,control and purification of PPR.[Methods]Soluble N protein and NH fusion protein were successfully obtained in an Escherichia coli expression system by optimizing E.coli codon and expression conditions.Furthermore,based on purified soluble N protein and NH fusion protein,a double-antigen sandwich time-resolved fluorescence immunoassay method for detection of peste des petits ruminants virus(PPRV)was established.[Results]The method has high sensitivity and specificity and can specifically detect the antibody against PPRV in sheep serum,and it has no cross reaction with other related diseases.The method was used to detect 292 clinical samples,and compared with French IDVET competition ELISA kit.The coincidence rates of positive samples and negative samples from the two kinds of test kits were 92.47%and 97.26%,respectively,and the overall coincidence rate was 94.86%.The intra-group and inter-group coefficients of variation in the repeatability test were less than 10%.[Conclusions]Compared with the traditional ELISA method,the double-antigen sandwich time-resolved fluorescence immunoassay for detection of PPRV has equivalent sensitivity and specificity,and simple and rapid operation,and thus high application and popularization value.展开更多
This study investigated the combinatorial expression of xanthine dehydrogenase(XDH)and chaperone XdhC from Acinetobacter baumannii and Rhodobacter capsulatus and their applications in decreasing purine content in the ...This study investigated the combinatorial expression of xanthine dehydrogenase(XDH)and chaperone XdhC from Acinetobacter baumannii and Rhodobacter capsulatus and their applications in decreasing purine content in the beer,beef and yeast.Naturally occurring xdhABC gene clusters of A.baumannii CICC 10254 and R.capsulatus CGMCC 1.3366 as well as two refactored clusters constructed by exchanging their xdhC genes were overexpressed in Escherichia coli and purified to near homogeneity.RcXDH chaperoned by AbXdhC showed nearly the same catalytic performance as that by RcXdhC,except for the decreased substrate affinity.While the AbXDH co-expressed with RcXdhC displayed enhanced acidic adaptation but weakened catalytic activity.All the XDHs degraded purines in beer,beef and yeast extract effectively,indicating potential applications in low-purine foods to prevent hyperuricemia and gout.The study also presents a method for exploiting the better chaperone XdhC and novel XDHs by functional complement activity using existing XdhCs such as RcXdhC.展开更多
文摘In dentistry, panoramic X-ray images are extensively used by dentists for tooth structure analysis and disease diagnosis. However, the manual analysis of these images is time-consuming and prone to misdiagnosis or overlooked. While deep learning techniques have been employed to segment teeth in panoramic X-ray images, accurate segmentation of individual teeth remains an underexplored area. In this study, we propose an end-to-end deep learning method that effectively addresses this challenge by employing an improved combinatorial loss function to separate the boundaries of adjacent teeth, enabling precise segmentation of individual teeth in panoramic X-ray images. We validate the feasibility of our approach using a challenging dataset. By training our segmentation network on 115 panoramic X-ray images, we achieve an intersection over union (IoU) of 86.56% for tooth segmentation and an accuracy of 65.52% in tooth counting on 87 test set images. Experimental results demonstrate the significant improvement of our proposed method in single tooth segmentation compared to existing methods.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2020MH138(to XZ).
文摘Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classically activated macrophage(M1)polarization.In this study,we established THP-1-derived testing state macrophages(M0),M1 macrophages,and alternately activated macrophages(M2).Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages.Flow cytometry was used to detect phenotypic proteins(CD11b,CD38,CD80).We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048.Flow cytometry,western blot,and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response,while over-expression of lnc_000048 led to the opposite effect.Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization.Moreover,catRAPID prediction,RNA-pull down,and mass spectrometry were used to identify and screen the protein kinase RNA-activated(PKR),then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR.Immunofluorescence(IF)-RNA fluorescence in situ hybridization(FISH)double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage.We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation,leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression.Taken together,these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.
基金supported by the Natural Science Foundation of Fujian Province of China(No.2022J01043)China Scholarship Council(201806315005 and 201703170071).
文摘Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.
基金supported by National Key Research and Development Program of China(2021YFB4000604)National Natural Science Foundation of China(52271220)111 Project(B12015)and the Fundamental Research Funds for the Central Universities.
文摘Hydrogen energy has emerged as a pivotal solution to address the global energy crisis and pave the way for a cleaner,low-carbon,secure,and efficient modern energy system.A key imperative in the utilization of hydrogen energy lies in the development of high-performance hydrogen storage materials.Magnesium-based hydrogen storage materials exhibit remarkable advantages,including high hydrogen storage density,cost-effectiveness,and abundant magnesium resources,making them highly promising for the hydrogen energy sector.Nonetheless,practical applications of magnesium hydride for hydrogen storage face significant challenges,primarily due to their slow kinetics and stable thermodynamic properties.Herein,we briefly summarize the thermodynamic and kinetic properties of MgH2,encompassing strategies such as alloying,nanoscaling,catalyst doping,and composite system construction to enhance its hydrogen storage performance.Notably,nanoscaling and catalyst doping have emerged as more effective modification strategies.The discussion focuses on the thermodynamic changes induced by nanoscaling and the kinetic enhancements resulting from catalyst doping.Particular emphasis lies in the synergistic improvement strategy of incorporating nanocatalysts with confinement materials,and we revisit typical works on the multi-strategy optimization of MgH2.In conclusion,we conduct an analysis of outstanding challenges and issues,followed by presenting future research and development prospects for MgH2 as hydrogen storage materials.
基金supported by the National Natural Science Foundation of China (31872261)the project of Northeast Asia Biodiversity Research Center (2572022DS09)the Fundamental Research Funds for the Central Universities (2572021DJ08,2572019CP11)。
基金funded by the National Natural Science Foundation of China(No.51974268)Open Fund of Key Laboratory of Ministry of Education for Improving Oil and Gas Recovery(NEPUEOR-2022-03)Research and Innovation Fund for Graduate Students of Southwest Petroleum University(No.2022KYCX005)。
文摘The oil production of the multi-fractured horizontal wells(MFHWs) declines quickly in unconventional oil reservoirs due to the fast depletion of natural energy. Gas injection has been acknowledged as an effective method to improve oil recovery factor from unconventional oil reservoirs. Hydrocarbon gas huff-n-puff becomes preferable when the CO_(2) source is limited. However, the impact of complex fracture networks and well interference on the EOR performance of multiple MFHWs is still unclear. The optimal gas huff-n-puff parameters are significant for enhancing oil recovery. This work aims to optimize the hydrocarbon gas injection and production parameters for multiple MFHWs with complex fracture networks in unconventional oil reservoirs. Firstly, the numerical model based on unstructured grids is developed to characterize the complex fracture networks and capture the dynamic fracture features.Secondly, the PVT phase behavior simulation was carried out to provide the fluid model for numerical simulation. Thirdly, the optimal parameters for hydrocarbon gas huff-n-puff were obtained. Finally, the dominant factors of hydrocarbon gas huff-n-puff under complex fracture networks are obtained by fuzzy mathematical method. Results reveal that the current pressure of hydrocarbon gas injection can achieve miscible displacement. The optimal injection and production parameters are obtained by single-factor analysis to analyze the effect of individual parameter. Gas injection time is the dominant factor of hydrocarbon gas huff-n-puff in unconventional oil reservoirs with complex fracture networks. This work can offer engineers guidance for hydrocarbon gas huff-n-puff of multiple MFHWs considering the complex fracture networks.
文摘The clinical application of magnesium(Mg)and its alloys for bone fractures has been well supported by in vitro and in vivo trials.However,there were studies indicating negative effects of high dose Mg intake and sustained local release of Mg ions on bone metabolism or repair,which should not be ignored when developing Mg-based implants.Thus,it remains necessary to assess the biological effects of Mg implants in animal models relevant to clinical treatment modalities.The primary purpose of this study was to validate the beneficial effects of intramedullary Mg implants on the healing outcome of femoral fractures in a modified rat model.In addition,the mineralization parameters at multiple anatomical sites were evaluated,to investigate their association with healing outcome and potential clinical applications.Compared to the control group without Mg implantation,postoperative imaging at week 12 demonstrated better healing outcomes in the Mg group,with more stable unions in 3D analysis and high-mineralized bridging in 2D evaluation.The bone tissue mineral density(TMD)was higher in the Mg group at the non-operated femur and lumbar vertebra,while no differences between groups were identified regarding the bone tissue volume(TV),TMD and bone mineral content(BMC)in humerus.In the surgical femur,the Mg group presented higher TMD,but lower TV and BMC in the distal metaphyseal region,as well as reduced BMC at the osteotomy site.Principal component analysis(PCA)-based machine learning revealed that by selecting clinically relevant parameters,radiological markers could be constructed for differentiation of healing outcomes,with better performance than 2D scoring.The study provides insights and preclinical evidence for the rational investigation of bioactive materials,the identification of potential adverse effects,and the promotion of diagnostic capabilities for fracture healing.
基金financially supported by National Natural Science Foundation of China(21701083)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX20_3137)。
文摘Solid polymer composite electrolytes possess the benefits of superior compatibility with electrodes and good thermal characteristics for more secure energy storage equipment.Herein,a new gel polymer electrolyte(GPE)containing NH_(2)-MIL-53(Al),[PP_(13)][TFSI],LiTFSI,and PVDF-HFP was prepared using a simple method of solution casting.The effects of encapsulating different ratios of ionic liquid([PP_(13)][TFSI])into the micropores of functionalized metal-organic frameworks(NH_(2)-MIL-53(Al))on the electrochemical properties were compared.XRD,SEM,nitrogen adsorption-desorption isotherms,and electrochemical measurements were conducted.This GPE demonstrates a superior ionic conductivity of 8.08×10^(-4)S·cm^(-1)at 60℃and can sustain a discharge specific capacity of 156.6 mA·h·g^(-1)at 0.2 C for over 100 cycles.This work might offer a potential approach to alleviate the solid-solid contact with the solid-state electrolyte and electrodes and broaden a new window for the creation of all-solid-state batteries.
基金support from the Ningxia Natural Science Foundation Project(2023AAC03361).
文摘The flying foxes optimization(FFO)algorithm,as a newly introduced metaheuristic algorithm,is inspired by the survival tactics of flying foxes in heat wave environments.FFO preferentially selects the best-performing individuals.This tendency will cause the newly generated solution to remain closely tied to the candidate optimal in the search area.To address this issue,the paper introduces an opposition-based learning-based search mechanism for FFO algorithm(IFFO).Firstly,this paper introduces niching techniques to improve the survival list method,which not only focuses on the adaptability of individuals but also considers the population’s crowding degree to enhance the global search capability.Secondly,an initialization strategy of opposition-based learning is used to perturb the initial population and elevate its quality.Finally,to verify the superiority of the improved search mechanism,IFFO,FFO and the cutting-edge metaheuristic algorithms are compared and analyzed using a set of test functions.The results prove that compared with other algorithms,IFFO is characterized by its rapid convergence,precise results and robust stability.
基金a grant from the state of Schleswig-Holstein and the European Union ERDF-European Regional Development Fund(Zukunftsprogramm Wirtschaft)。
文摘Historically,the rapid degradation and massive gas release from magnesium(Mg)implants resulted in severe emphysema and mechanical failure.With the advent of new alloys and surface treatment methods,optimized Mg implants have re-entered clinics since last decade with reliable performance.However,the optimization aims at slowing down the degradation process,rather than exemption of the gas release.This study involved a systematic evaluation of current preclinical and clinical evidence,regarding the physical signs,symptoms,radiological features,pathological findings and complications potentially associated with peri±implant gas accumulation(PIGA)after musculoskeletal Mg implantation.The literature search identified 196 potentially relevant publications,and 51 papers were enrolled for further analysis,including 22 preclinical tests and 29 clinical studies published from 2005 to 2023.Various Mg-based materials have been evaluated in animal research,and the application of pure Mg and Mg alloys have been reported in clinical follow-ups involving multiple anatomical sites and musculoskeletal disorders.Soft tissue and intraosseous PIGA are common in both animal tests and clinical follow-ups,and potentially associated with certain adverse events.Radiological examinations especially micro-CT and clinical CT scans provide valuable information for quantitative and longitudinal analysis.While according to simulation tests involving Mg implantation and chemical processing,tissue fixation could lead to an increase in the volume of gas cavity,thus the results obtained from ex vivo imaging or histopathological evaluations should be interpreted with caution.There still lacks standardized procedures or consensus for both preclinical and clinical evaluation of PIGA.However,by providing focused insights into the topic,this evidence-based study will facilitate future animal tests and clinical evaluations,and support developing biocompatible Mg implants for the treatment of musculoskeletal disorders.
基金supported by the Major Program of National Natural Science Foundation of China (No. 91959205)National Natural Science Foundation of China (No. 82141117)+3 种基金The Capital’s Funds for Health Improvement and Research (CFH) (No. 2022-2-1023)Beijing Xisike Clinical Oncology Research Foundation Ypierrefabre (No. 202101-0099)Beijing Municipal Administration of Hospitals Incubating Program (No. PX2020045)Science Foundation of Peking University Cancer Hospital (No. 2020-4)。
文摘Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.
文摘BACKGROUND Gastric cancer is a common malignant tumor of the digestive system worldwide,and its early diagnosis is crucial to improve the survival rate of patients.Indocyanine green fluorescence imaging(ICG-FI),as a new imaging technology,has shown potential application prospects in oncology surgery.The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice.AIM To assess the diagnostic efficacy of optical imaging in conjunction with indocya-nine green(ICG)-guided sentinel lymph node(SLN)biopsy for gastric cancer.METHODS Electronic databases such as PubMed,Embase,Medline,Web of Science,and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy.Stata 12.0 software was used for analysis by combining the"bivariable mixed effect model"with the"midas"command.The true positive value,false positive value,false negative value,true negative value,and other information from the included literature were extracted.A literature quality assessment map was drawn to describe the overall quality of the included literature.A forest plot was used for heterogeneity analysis,and P<0.01 was considered to indicate statistical significance.A funnel plot was used to assess publication bias,and P<0.1 was considered to indicate statistical significance.The summary receiver operating characteristic(SROC)curve was used to calculate the area under the curve(AUC)to determine the diagnostic accuracy.If there was interstudy heterogeneity(I2>50%),meta-regression analysis and subgroup analysis were performed.analysis were performed.RESULTS Optical imaging involves two methods:Near-infrared(NIR)imaging and fluorescence imaging.A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis.The positive likelihood ratio was 30.39(95%CI:0.92-1.00),the sensitivity was 0.95(95%CI:0.82-0.99),and the specificity was 1.00(95%CI:0.92-1.00).The negative likelihood ratio was 0.05(95%CI:0.01-0.20),the diagnostic odds ratio was 225.54(95%CI:88.81-572.77),and the SROC AUC was 1.00(95%CI:The crucial values were sensitivity=0.95(95%CI:0.82-0.99)and specificity=1.00(95%CI:0.92-1.00).The Deeks method revealed that the"diagnostic odds ratio"funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical(P=0.01),suggesting significant publication bias.Further meta-subgroup analysis revealed that,compared with fluorescence imaging,NIR imaging had greater sensitivity(0.98 vs 0.73).Compared with optical imaging immediately after ICG injection,optical imaging after 20 minutes obtained greater sensitivity(0.98 vs 0.70).Compared with that of patients with an average SLN detection number<4,the sensitivity of patients with a SLN detection number≥4 was greater(0.96 vs 0.68).Compared with hematoxylin-eosin(HE)staining,immunohistochemical(+HE)staining showed greater sensitivity(0.99 vs 0.84).Compared with subserous injection of ICG,submucosal injection achieved greater sensitivity(0.98 vs 0.40).Compared with 5 g/L ICG,0.5 and 0.05 g/L ICG had greater sensitivity(0.98 vs 0.83),and cT1 stage had greater sensitivity(0.96 vs 0.72)than cT2 to cT3 clinical stage.Compared with that of patients≤26,the sensitivity of patients>26 was greater(0.96 vs 0.65).Compared with the literature published before 2010,the sensitivity of the literature published after 2010 was greater(0.97 vs 0.81),and the differences were statistically significant(all P<0.05).CONCLUSION For the diagnosis of stomach cancer,optical imaging in conjunction with ICG-guided SLN biopsy is a therapeut-ically viable approach,especially for early gastric cancer.The concentration of ICG used in the SLN biopsy of gastric cancer may be too high.Moreover,NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.
基金Supported by The National Project for the Prevention and Control of Major Exotic Animal Diseases(2022YFD1800500)National Mutton Sheep Industrial Technology System(CARS39).
文摘[Objectives]This study was conducted to establish a rapid quantitative method for detecting antibody against Peste des Petits Ruminants Virus(PPR V)in sheep serum.[Methods]Soluble N protein and NH fusion protein were obtained in Escherichia coli prokaryotic expression system by optimizing codons and expression conditions of E.coli.Furthermore,based on the purified soluble N protein and NH fusion protein,a high-sensitivity fluorescence immunoassay kit for detecting the antibody against PPR V was established.[Results]The method could quickly and quantitatively detect PPR V antibody in sheep serum,with high sensitivity and specificity,without any cross reaction to other related sheep pathogens.The intra-batch and inter-batch coefficients of variation were less than 10%and 15%,respectively,and the method had good repeatability.Through detection on 292 clinical serum samples,it was compared with the French IDVET competitive ELISA kit,and the coincidence rate of the two methods reached 93.84%.Compared with the serum neutralization test,the detected titer value of the high-sensitivity rapid fluorescence quantitative detection method was basically consistent with the tilter value obtained by the neutralization test on the standard positive serum(provided by the WOAH Brucellosis Reference Laboratory of France).[Conclusions]This method can realize rapid quantitative detection of PPR V antibody on site,and has high practical value and popularization value.
基金Supported by National Key R&D Program for the Prevention and Control of Major Exotic Animal Diseases(2022YFD1800500)National Mutton Sheep Industrial Technology System(CARS39)+2 种基金Key Research and Development Program of Shandong Province(Major Science and Technology Innovation Project)(2021CXGC011306)Scientific Research Project of General Administration of Customs(2024HK033)Scientific Research Project of Jinan Customs(2023JK005).
文摘[Objectives]This study was conducted to explore rapid and large-scale screening and detection of peste des petits ruminants(PPR),so as to provide important technical means for prevention,control and purification of PPR.[Methods]Soluble N protein and NH fusion protein were successfully obtained in an Escherichia coli expression system by optimizing E.coli codon and expression conditions.Furthermore,based on purified soluble N protein and NH fusion protein,a double-antigen sandwich time-resolved fluorescence immunoassay method for detection of peste des petits ruminants virus(PPRV)was established.[Results]The method has high sensitivity and specificity and can specifically detect the antibody against PPRV in sheep serum,and it has no cross reaction with other related diseases.The method was used to detect 292 clinical samples,and compared with French IDVET competition ELISA kit.The coincidence rates of positive samples and negative samples from the two kinds of test kits were 92.47%and 97.26%,respectively,and the overall coincidence rate was 94.86%.The intra-group and inter-group coefficients of variation in the repeatability test were less than 10%.[Conclusions]Compared with the traditional ELISA method,the double-antigen sandwich time-resolved fluorescence immunoassay for detection of PPRV has equivalent sensitivity and specificity,and simple and rapid operation,and thus high application and popularization value.
基金funded by the National Natural Science Foundation of China(21868003)the Guangxi Natural Science Foundation(2018AD19022,2017GXNSFAA198265)the Nanning Science and Technology Development Project(2017014).
文摘This study investigated the combinatorial expression of xanthine dehydrogenase(XDH)and chaperone XdhC from Acinetobacter baumannii and Rhodobacter capsulatus and their applications in decreasing purine content in the beer,beef and yeast.Naturally occurring xdhABC gene clusters of A.baumannii CICC 10254 and R.capsulatus CGMCC 1.3366 as well as two refactored clusters constructed by exchanging their xdhC genes were overexpressed in Escherichia coli and purified to near homogeneity.RcXDH chaperoned by AbXdhC showed nearly the same catalytic performance as that by RcXdhC,except for the decreased substrate affinity.While the AbXDH co-expressed with RcXdhC displayed enhanced acidic adaptation but weakened catalytic activity.All the XDHs degraded purines in beer,beef and yeast extract effectively,indicating potential applications in low-purine foods to prevent hyperuricemia and gout.The study also presents a method for exploiting the better chaperone XdhC and novel XDHs by functional complement activity using existing XdhCs such as RcXdhC.
