BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascu...BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.展开更多
Tropical forests store more than half of the world's terrestrial carbon(C)pool and account for one-third of global net primary productivity(NPP).Many terrestrial biosphere models(TBMs)estimate increased productivi...Tropical forests store more than half of the world's terrestrial carbon(C)pool and account for one-third of global net primary productivity(NPP).Many terrestrial biosphere models(TBMs)estimate increased productivity in tropical forests throughout the 21st century due to CO_(2)fertilization.However,phosphorus(P)liaitations on vegetation photosynthesis and productivity could significantly reduce the CO_(2)fertilization effect.Here,we used a carbon-nitrogen-phosphorus coupled model(Dynamic Land Ecosystem Model;DLEM-CNP)with heterogeneous maximum carboxylation rates to examine how P limitation has affected C fluxes in tropical forests during1860-2018.Our model results showed that the inclusion of the P processes enhanced model performance in simulating ecosystem productivity.We further compared the simulations from DLEM-CNP,DLEM-CN,and DLEMC and the results showed that the inclusion of P processes reduced the CO_(2)fertilization effect on gross primary production(GPP)by 25%and 45%,and net ecosystem production(NEP)by 28%and 41%,respectively,relative to CN-only and C-on ly models.From the 1860s to the 2010s,the DLEM-CNP estimated that in tropical forests GPP increased by 17%,plant respiration(Ra)increased by 18%,ecosystem respiration(Rh)increased by 13%,NEP increased by 121%per unit area,respectively.Additionally,factorial experiments with DLEM-CNP showed that the enhanced NPP benefiting from the CO_(2) fertilization effect had been offset by 135%due to deforestation from the 1860s to the 2010s.Our study highlights the importance of P limitation on the C cycle and the weakened CO_(2)fertilization effect resulting from P limitation in tropical forests.展开更多
Under the policy background and advocacy of carbon capture,utilization,and storage(CCUS),CO_(2)-EOR has become a promising direction in the shale oil reservoir industry.The multi-scale pore structure distribution and ...Under the policy background and advocacy of carbon capture,utilization,and storage(CCUS),CO_(2)-EOR has become a promising direction in the shale oil reservoir industry.The multi-scale pore structure distribution and fracture structure lead to complex multiphase flow,comprehensively considering multiple mechanisms is crucial for development and CO_(2) storage in fractured shale reservoirs.In this paper,a multi-mechanism coupled model is developed by MATLAB.Compared to the traditional Eclipse300 and MATLAB Reservoir Simulation Toolbox(MRST),this model considers the impact of pore structure on fluid phase behavior by the modified Peng—Robinson equation of state(PR-EOS),and the effect simultaneously radiate to Maxwell—Stefan(M—S)diffusion,stress sensitivity,the nano-confinement(NC)effect.Moreover,a modified embedded discrete fracture model(EDFM)is used to model the complex fractures,which optimizes connection types and half-transmissibility calculation approaches between non-neighboring connections(NNCs).The full implicit equation adopts the finite volume method(FVM)and Newton—Raphson iteration for discretization and solution.The model verification with the Eclipse300 and MRST is satisfactory.The results show that the interaction between the mechanisms significantly affects the production performance and storage characteristics.The effect of molecular diffusion may be overestimated in oil-dominated(liquid-dominated)shale reservoirs.The well spacing and injection gas rate are the most crucial factors affecting the production by sensitivity analysis.Moreover,the potential gas invasion risk is mentioned.This model provides a reliable theoretical basis for CO_(2)-EOR and sequestration in shale oil reservoirs.展开更多
High Mountain Asia(HMA),recognized as a third pole,needs regular and intense studies as it is susceptible to climate change.An accurate and high-resolution Digital Elevation Model(DEM)for this region enables us to ana...High Mountain Asia(HMA),recognized as a third pole,needs regular and intense studies as it is susceptible to climate change.An accurate and high-resolution Digital Elevation Model(DEM)for this region enables us to analyze it in a 3D environment and understand its intricate role as the Water Tower of Asia.The science teams of NASA realized an 8-m DEM using satellite stereo imagery for HMA,termed HMA 8-m DEM.In this research,we assessed the vertical accuracy of HMA 8-m DEM using reference elevations from ICESat-2 geolocated photons at three test sites of varied topography and land covers.Inferences were made from statistical quantifiers and elevation profiles.For the world’s highest mountain,Mount Everest,and its surroundings,Root Mean Squared Error(RMSE)and Mean Absolute Error(MAE)resulted in 1.94 m and 1.66 m,respectively;however,a uniform positive bias observed in the elevation profiles indicates the seasonal snow cover change will dent the accurate estimation of the elevation in this sort of test sites.The second test site containing gentle slopes with forest patches has exhibited the Digital Surface Model(DSM)features with RMSE and MAE of 0.58 m and 0.52 m,respectively.The third test site,situated in the Zanda County of the Qinghai-Tibet,is a relatively flat terrain bed,mostly bare earth with sudden river cuts,and has minimal errors with RMSE and MAE of 0.32 m and 0.29 m,respectively,and with a negligible bias.Additionally,in one more test site,the feasibility of detecting the glacial lakes was tested,which resulted in exhibiting a flat surface over the surface of the lakes,indicating the potential of HMA 8-m DEM for deriving the hydrological parameters.The results accrued in this investigation confirm that the HMA 8-m DEM has the best vertical accuracy and should be of high use for analyzing natural hazards and monitoring glacier surfaces.展开更多
Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional p...Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin.展开更多
From June 2008 to August 2013,approximately 67 kt of CO_(2) was injected into a deep saline formation at the Ketzin pilot CO_(2) storage site.During injection,3D seismic surveys have been performed to monitor the migr...From June 2008 to August 2013,approximately 67 kt of CO_(2) was injected into a deep saline formation at the Ketzin pilot CO_(2) storage site.During injection,3D seismic surveys have been performed to monitor the migration of sequestered CO_(2).Seismic monitoring results are limited by the acquisition and signal-to-noise ratio of the acquired data.The multiphysical reservoir simulation provides information regarding the CO_(2) fluid behavior,and the approximated model should be calibrated with the monitoring results.In this work,property models are delivered from the multiphysical model during 3D repeated seismic surveys.The simulated seismic data based on the models are compared with the real data,and the results validate the effectiveness of the multiphysical inversion method.Time-lapse analysis shows the trend of CO_(2) migration during and after injection.展开更多
Metal–N–C single‐atom catalysts,mostly prepared from pyrolysis of metalorganic precursors,are widely used in heterogeneous electrocatalysis.Since metal sites with diverse local structures coexist in this type of ma...Metal–N–C single‐atom catalysts,mostly prepared from pyrolysis of metalorganic precursors,are widely used in heterogeneous electrocatalysis.Since metal sites with diverse local structures coexist in this type of material and it is challenging to characterize the local structure,a reliable structure–property relationship is difficult to establish.Conjugated macrocyclic complexes adsorbed on carbon support are well‐defined models to mimic the singleatom catalysts.Metal–N_(4)site with four electroneutral pyridine‐type ligands embedded in a graphene layer is the most commonly proposed structure of the active site of single‐atom catalysts,but its molecular counterpart has not been reported.In this work,we synthesized the conjugated macrocyclic complexes with a metal center(Co,Fe,or Ni)coordinated with four electroneutral pyridinic ligands as model catalysts for CO_(2)electroreduction.For comparison,the complexes with anionic quadri‐pyridine macrocyclic ligand were also prepared.The Co complex with the electroneutral ligand expressed a turnover frequency of CO formation more than an order of magnitude higher than that of the Co complex with the anionic ligand.Constrained ab initio molecular dynamics simulations based on the well‐defined structures of the model catalysts indicate that the Co complex with the electroneutral ligand possesses a stronger ability to mediate electron transfer from carbon to CO_(2).展开更多
This research aims to optimize the utilization of long-term sea level data from the TOPEX/Poseidon,Jason1,Jason2,and Jason3 altimetry missions for tidal modeling.We generate a time series of along-track observations a...This research aims to optimize the utilization of long-term sea level data from the TOPEX/Poseidon,Jason1,Jason2,and Jason3 altimetry missions for tidal modeling.We generate a time series of along-track observations and apply a developed method to produce tidal models with specific tidal constituents for each location.Our tidal modeling methodology follows an iterative process:partitioning sea surface height(SSH)observations into analysis/training and prediction/validation parts and ultimately identi-fying the set of tidal constituents that provide the best predictions at each time series location.The study focuses on developing 1256 time series along the altimetry tracks over the Baltic Sea,each with its own set of tidal constituents.Verification of the developed tidal models against the sSH observations within the prediction/validation part reveals mean absolute error(MAE)values ranging from 0.0334 m to 0.1349 m,with an average MAE of 0.089 m.The same validation process is conducted on the FES2014 and EOT20 global tidal models,demonstrating that our tidal model,referred to as BT23(short for Baltic Tide 2023),outperforms both models with an average MAE improvement of 0.0417 m and 0.0346 m,respectively.In addition to providing details on the development of the time series and the tidal modeling procedure,we offer the 1256 along-track time series and their associated tidal models as supplementary materials.We encourage the satellite altimetry community to utilize these resources for further research and applications.展开更多
BACKGROUND Diabetic foot(DF)is a serious complication of type 2 diabetes.This study aimed to investigate the factors associated with DF occurrence and the role of delayed medical care in a cohort of patients with type...BACKGROUND Diabetic foot(DF)is a serious complication of type 2 diabetes.This study aimed to investigate the factors associated with DF occurrence and the role of delayed medical care in a cohort of patients with type 2 diabetes.AIM To reveal the impact of delayed medical treatment on the development of DF in patients with type 2 diabetes and to establish a predictive model for DF.METHODS In this retrospective cohort study,292 patients with type 2 diabetes who underwent examination at our hospital from January 2023 to December 2023 were selected and divided into the DF group(n=82,DF)and nondiabetic foot group(n=210,NDF).Differential and correlation analyses of demographic indicators,laboratory parameters,and delayed medical treatment were conducted for the two groups.Logistic regression was applied to determine influencing factors.Receiver operating characteristic(ROC)analysis was performed,and indicators with good predictive value were selected to establish a combined predictive model.RESULTS The DF group had significantly higher body mass index(BMI)(P<0.001),disease duration(P=0.012),plasma glucose levels(P<0.001),and HbA1c(P<0.001)than the NDF group.The NDF group had significantly higher Acute Thrombosis and Myocardial Infarction Health Service System(ATMHSS)scores(P<0.001)and a significantly lower delayed medical treatment rate(72.38%vs 13.41%,P<0.001).BMI,duration of diabetes,plasma glucose levels,HbA1c,diabetic peripheral neuropathy,and nephropathy were all positively correlated with DF occurrence.ATMHSS scores were negatively correlated with delayed time to seek medical treatment.The logistic regression model revealed that BMI,duration of diabetes,plasma glucose levels,HbA1c,presence of diabetic peripheral neuropathy and nephropathy,ATMHSS scores,and delayed time to seek medical treatment were influencing factors for DF.ROC analysis indicated that plasma glucose levels,HbA1c,and delayed medical treatment had good predictive value with an area under the curve of 0.933 for the combined predictive model.CONCLUSION Delayed medical treatment significantly affects the probability of DF occurrence in patients with diabetes.Plasma glucose levels,HbA1c levels,and the combined predictive model of delayed medical treatment demonstrate good predictive value.展开更多
Background,aim,and scope The tectonic uplift of the Cenozoic Tibetan Plateau has produced a chain effect,which is an excellent location for Earth system science research,and its uplift process,mechanism and environmen...Background,aim,and scope The tectonic uplift of the Cenozoic Tibetan Plateau has produced a chain effect,which is an excellent location for Earth system science research,and its uplift process,mechanism and environmental effects are the hot spot and frontier of the current research.The“Tibetan Plateau uplift-weathering-CO_(2)concentration-global climate change”model was put forward by Raymo and Ruddiman to interpret the Late Cenozoic climate change.However,there are still some questions suspended,such as does the weathering of the Tibetan Plateau have the ability to control the global climate?How to explain the modern-like global CO_(2)concentration starting at about 24 Ma?Here,a short space was taken to present a brainstorm about the above questions on account of existing geological pieces of evidence.Materials and methods In this paper,we integrate the formation and evolution of the Yangtze River and Pearl River,the origin and development of the Asian inland aridification-monsoon system,the Cenozoic tectonic uplift process of the Tibetan Plateau,and the westerly winds to discuss and analyze the relationship between the Cenozoic CO_(2)concentration changes and the uplift of the Tibetan Plateau and why the CO_(2)concentration similar to the present was formed at about 24 Ma.Results Similar correspondence of the surface uplift history of Xizang,other global mountains,and the declining CO_(2)concentration could support the theory Tibetan Plateau weathering inf luences CO_(2)concentration.Starting from 24 Ma,the most important character was the uplift and erosion of Xizang and Himalaya,collaborating with Ocean Iron Fertilization(OIF)together as an entity to control the atmospheric CO_(2)concentration because the great Asian rivers,Asian monsoons,and westerlies connected Xizang and surrounded seas together through materials transportation.Discussion Paleogeographic reconstructions from 40 Ma to 20 Ma illustrate that the main topographic change occurred in the Andes,Cordillera orogenic belt,and Xizang.We comprise a comprehensive set of evidence from independent data,which correspond temporally with the tipping point(about 24 Ma)of the atmospheric CO_(2)and we noticed that modern-like Asia monsoon,inland aridity,Asian great rivers,and climate zone formed at about 24 Ma and also there are tectonic activities for the Andes and Rockies.We raised the possibility that the modern-like atmospheric CO_(2)concentration at about 24 Ma was caused by the above geological factors.Here the rivers,monsoon,and westerlies are termed as“connectors”.In addition,these Asian rivers originated from Xizang,the monsoon,and inner Asian aridification are strongly a function of the uplift and growth of Xizang,thus,Xizang here is named as“trigger”.The distinct character of“trigger-connectors”model is that this not only takes the monsoon,westerlies,and the global great rivers into consideration but also expands the range which inf luences atmospheric CO_(2)concentration,from local points to a vast area since about 24 Ma,such as from Tibetan Plateau to Asia,including surrounded seas,after about 24 Ma.However,because the opening of the Late Oligocene-Early Miocene Antarctic periphery straits is highly coincident with the onset of modern-like global atmospheric CO_(2)concentration,we are forced to consider that they also had a significant impact on the reduction of atmospheric CO_(2)concentrations at this time.Conclusions“Trigger-connectors”was put forward to explain the Cenozoic CO_(2)variation,especially modern-like global CO_(2)concentration since about 24 Ma.Recommendations and perspectives Here we use the“trigger-connectors”model to explain the formation of modern-like CO_(2)concentrations starting at about 24 Ma,but there are still some problems.The most important premise for the“trigger-connectors”model is the constructed Cenozoic CO_(2)concentration record is reliable,which is the foundation of our hypothesis.In the future,potential improvements should focus on topographic reconstructions of Xizang and the global mountains.Here we have concentrated on Xizang in the considered timeslices but still,pay less attention to other global orogenic belts.Collaborations with geologist experts in those regions could provide valuable feedback to evaluate their potential role of them in CO_(2)evolution.What is more,considerable progress may be achieved with the addition and consideration of more and new geological data.展开更多
Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to creat...Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PT...Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.展开更多
Background:Myocardial infarction(MI)is known worldwide for its important disabling features,including myocarditis and cardiomyocyte apoptosis.It is believed that microRNA(miRNA)has a role in the cellular processes of ...Background:Myocardial infarction(MI)is known worldwide for its important disabling features,including myocarditis and cardiomyocyte apoptosis.It is believed that microRNA(miRNA)has a role in the cellular processes of apoptosis and myocarditis,and miR-219a-5p has been found to suppress the inflammatory response.However,unknown is the precise mechanism by which miR-219a-5p contributes to MI.Methods:We measured the expression of miR-219a-5p and evaluated its effects on target proteins,inflammatory factors,and apoptosis in a mouse model of MI.Echocardiography was utilized to examine the MI clinical index,and triphenyl tetrazolium chloride staining was employed to analyze the infarcted region.Enzyme-linked immunosorbent assay and Western blotting measured serum and molecular markers in heart tissues.To quantify the association with miR-219a-5p and ATPase sarcoplasmic/endoplasmic reticulum Ca^(2+)transporting 2(ATP2A2),the luciferase activity assay and Pearson’s correlation analysis were employed.Results:MiR-219a-5p exhibited low expression in a mouse model of MI,and its amplification prevented both apoptotic and inflammatory reactions.Specifically,miR-219a-5p targeted ATP2A2.Conclusion:In a mouse model of MI,miR-219a-5p exerted a potent protective effect via direct targeting of ATP2A2.展开更多
基金The study was reviewed and approved by the First People’s Hospital of Wenling(Approval No.KY-2023-2034-01).
文摘BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.
基金partially supported by the US National Science Foundation(1903722,1243232)。
文摘Tropical forests store more than half of the world's terrestrial carbon(C)pool and account for one-third of global net primary productivity(NPP).Many terrestrial biosphere models(TBMs)estimate increased productivity in tropical forests throughout the 21st century due to CO_(2)fertilization.However,phosphorus(P)liaitations on vegetation photosynthesis and productivity could significantly reduce the CO_(2)fertilization effect.Here,we used a carbon-nitrogen-phosphorus coupled model(Dynamic Land Ecosystem Model;DLEM-CNP)with heterogeneous maximum carboxylation rates to examine how P limitation has affected C fluxes in tropical forests during1860-2018.Our model results showed that the inclusion of the P processes enhanced model performance in simulating ecosystem productivity.We further compared the simulations from DLEM-CNP,DLEM-CN,and DLEMC and the results showed that the inclusion of P processes reduced the CO_(2)fertilization effect on gross primary production(GPP)by 25%and 45%,and net ecosystem production(NEP)by 28%and 41%,respectively,relative to CN-only and C-on ly models.From the 1860s to the 2010s,the DLEM-CNP estimated that in tropical forests GPP increased by 17%,plant respiration(Ra)increased by 18%,ecosystem respiration(Rh)increased by 13%,NEP increased by 121%per unit area,respectively.Additionally,factorial experiments with DLEM-CNP showed that the enhanced NPP benefiting from the CO_(2) fertilization effect had been offset by 135%due to deforestation from the 1860s to the 2010s.Our study highlights the importance of P limitation on the C cycle and the weakened CO_(2)fertilization effect resulting from P limitation in tropical forests.
基金supported by the National Natural Science Foundation of China(No.52174038 and No.52004307)China Petroleum Science and Technology Project-Major Project-Research on Tight Oil-Shale Oil Reservoir Engineering Methods and Key Technologies in Ordos Basin(No.ZLZX2020-02-04)Science Foundation of China University of Petroleum,Beijing(No.2462018YJRC015)。
文摘Under the policy background and advocacy of carbon capture,utilization,and storage(CCUS),CO_(2)-EOR has become a promising direction in the shale oil reservoir industry.The multi-scale pore structure distribution and fracture structure lead to complex multiphase flow,comprehensively considering multiple mechanisms is crucial for development and CO_(2) storage in fractured shale reservoirs.In this paper,a multi-mechanism coupled model is developed by MATLAB.Compared to the traditional Eclipse300 and MATLAB Reservoir Simulation Toolbox(MRST),this model considers the impact of pore structure on fluid phase behavior by the modified Peng—Robinson equation of state(PR-EOS),and the effect simultaneously radiate to Maxwell—Stefan(M—S)diffusion,stress sensitivity,the nano-confinement(NC)effect.Moreover,a modified embedded discrete fracture model(EDFM)is used to model the complex fractures,which optimizes connection types and half-transmissibility calculation approaches between non-neighboring connections(NNCs).The full implicit equation adopts the finite volume method(FVM)and Newton—Raphson iteration for discretization and solution.The model verification with the Eclipse300 and MRST is satisfactory.The results show that the interaction between the mechanisms significantly affects the production performance and storage characteristics.The effect of molecular diffusion may be overestimated in oil-dominated(liquid-dominated)shale reservoirs.The well spacing and injection gas rate are the most crucial factors affecting the production by sensitivity analysis.Moreover,the potential gas invasion risk is mentioned.This model provides a reliable theoretical basis for CO_(2)-EOR and sequestration in shale oil reservoirs.
基金The authors gratefully acknowledge the science teams of NASA High Mountain Asia 8-meter DEM and NASA ICESat-2 for providing access to the data.This work was conducted with the infrastructure provided by the National Remote Sensing Centre(NRSC),for which the authors were indebted to the Director,NRSC,Hyderabad.We acknowledge the continued support and scientific insights from Mr.Rakesh Fararoda,Mr.Sagar S Salunkhe,Mr.Hansraj Meena,Mr.Ashish K.Jain and other staff members of Regional Remote Sensing Centre-West,NRSC/ISRO,Jodhpur.The authors want to acknowledge Dr.Kamal Pandey,Scientist,IIRS,Dehradun,for sharing field-level information about the Auli-Joshimath.This research did not receive any specific grant from funding agencies in the public,commercial,or not-for-profit sectors.
文摘High Mountain Asia(HMA),recognized as a third pole,needs regular and intense studies as it is susceptible to climate change.An accurate and high-resolution Digital Elevation Model(DEM)for this region enables us to analyze it in a 3D environment and understand its intricate role as the Water Tower of Asia.The science teams of NASA realized an 8-m DEM using satellite stereo imagery for HMA,termed HMA 8-m DEM.In this research,we assessed the vertical accuracy of HMA 8-m DEM using reference elevations from ICESat-2 geolocated photons at three test sites of varied topography and land covers.Inferences were made from statistical quantifiers and elevation profiles.For the world’s highest mountain,Mount Everest,and its surroundings,Root Mean Squared Error(RMSE)and Mean Absolute Error(MAE)resulted in 1.94 m and 1.66 m,respectively;however,a uniform positive bias observed in the elevation profiles indicates the seasonal snow cover change will dent the accurate estimation of the elevation in this sort of test sites.The second test site containing gentle slopes with forest patches has exhibited the Digital Surface Model(DSM)features with RMSE and MAE of 0.58 m and 0.52 m,respectively.The third test site,situated in the Zanda County of the Qinghai-Tibet,is a relatively flat terrain bed,mostly bare earth with sudden river cuts,and has minimal errors with RMSE and MAE of 0.32 m and 0.29 m,respectively,and with a negligible bias.Additionally,in one more test site,the feasibility of detecting the glacial lakes was tested,which resulted in exhibiting a flat surface over the surface of the lakes,indicating the potential of HMA 8-m DEM for deriving the hydrological parameters.The results accrued in this investigation confirm that the HMA 8-m DEM has the best vertical accuracy and should be of high use for analyzing natural hazards and monitoring glacier surfaces.
基金jointly funded by projects supported by the National Natural Science Foundation of China(Grant No.41872150)the Joint Funds of the National Natural Science Foundation of China(Grant No.U19B6003)Major Scientific and Technological Projects of CNPC during the 13th five-year plan(No.2019A-02-10)。
文摘Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin.
基金supported by the National Natural Science Foundation of China(Grant No.42025403)the Youth Innovation Promotion Association,Chinese Academy of Sciences(Grant No.2023074).
文摘From June 2008 to August 2013,approximately 67 kt of CO_(2) was injected into a deep saline formation at the Ketzin pilot CO_(2) storage site.During injection,3D seismic surveys have been performed to monitor the migration of sequestered CO_(2).Seismic monitoring results are limited by the acquisition and signal-to-noise ratio of the acquired data.The multiphysical reservoir simulation provides information regarding the CO_(2) fluid behavior,and the approximated model should be calibrated with the monitoring results.In this work,property models are delivered from the multiphysical model during 3D repeated seismic surveys.The simulated seismic data based on the models are compared with the real data,and the results validate the effectiveness of the multiphysical inversion method.Time-lapse analysis shows the trend of CO_(2) migration during and after injection.
基金Guangdong Grants,Grant/Award Number:2021ZT09C064National Natural Science Foundation of China,Grant/Award Numbers:22272073,22373045,22373045+2 种基金Shenzhen Science and Technology Program,Grant/Award Numbers:JCYJ20210324104414039,JCYJ20220818100410023,KCXST20221021111207017Guangdong Basic and Applied Basic Research Foundation,Grant/Award Numbers:2021A1515110360,2022A1515011976China Postdoctoral Science Foundation,Grant/Award Number:2022M721469。
文摘Metal–N–C single‐atom catalysts,mostly prepared from pyrolysis of metalorganic precursors,are widely used in heterogeneous electrocatalysis.Since metal sites with diverse local structures coexist in this type of material and it is challenging to characterize the local structure,a reliable structure–property relationship is difficult to establish.Conjugated macrocyclic complexes adsorbed on carbon support are well‐defined models to mimic the singleatom catalysts.Metal–N_(4)site with four electroneutral pyridine‐type ligands embedded in a graphene layer is the most commonly proposed structure of the active site of single‐atom catalysts,but its molecular counterpart has not been reported.In this work,we synthesized the conjugated macrocyclic complexes with a metal center(Co,Fe,or Ni)coordinated with four electroneutral pyridinic ligands as model catalysts for CO_(2)electroreduction.For comparison,the complexes with anionic quadri‐pyridine macrocyclic ligand were also prepared.The Co complex with the electroneutral ligand expressed a turnover frequency of CO formation more than an order of magnitude higher than that of the Co complex with the anionic ligand.Constrained ab initio molecular dynamics simulations based on the well‐defined structures of the model catalysts indicate that the Co complex with the electroneutral ligand possesses a stronger ability to mediate electron transfer from carbon to CO_(2).
文摘This research aims to optimize the utilization of long-term sea level data from the TOPEX/Poseidon,Jason1,Jason2,and Jason3 altimetry missions for tidal modeling.We generate a time series of along-track observations and apply a developed method to produce tidal models with specific tidal constituents for each location.Our tidal modeling methodology follows an iterative process:partitioning sea surface height(SSH)observations into analysis/training and prediction/validation parts and ultimately identi-fying the set of tidal constituents that provide the best predictions at each time series location.The study focuses on developing 1256 time series along the altimetry tracks over the Baltic Sea,each with its own set of tidal constituents.Verification of the developed tidal models against the sSH observations within the prediction/validation part reveals mean absolute error(MAE)values ranging from 0.0334 m to 0.1349 m,with an average MAE of 0.089 m.The same validation process is conducted on the FES2014 and EOT20 global tidal models,demonstrating that our tidal model,referred to as BT23(short for Baltic Tide 2023),outperforms both models with an average MAE improvement of 0.0417 m and 0.0346 m,respectively.In addition to providing details on the development of the time series and the tidal modeling procedure,we offer the 1256 along-track time series and their associated tidal models as supplementary materials.We encourage the satellite altimetry community to utilize these resources for further research and applications.
文摘BACKGROUND Diabetic foot(DF)is a serious complication of type 2 diabetes.This study aimed to investigate the factors associated with DF occurrence and the role of delayed medical care in a cohort of patients with type 2 diabetes.AIM To reveal the impact of delayed medical treatment on the development of DF in patients with type 2 diabetes and to establish a predictive model for DF.METHODS In this retrospective cohort study,292 patients with type 2 diabetes who underwent examination at our hospital from January 2023 to December 2023 were selected and divided into the DF group(n=82,DF)and nondiabetic foot group(n=210,NDF).Differential and correlation analyses of demographic indicators,laboratory parameters,and delayed medical treatment were conducted for the two groups.Logistic regression was applied to determine influencing factors.Receiver operating characteristic(ROC)analysis was performed,and indicators with good predictive value were selected to establish a combined predictive model.RESULTS The DF group had significantly higher body mass index(BMI)(P<0.001),disease duration(P=0.012),plasma glucose levels(P<0.001),and HbA1c(P<0.001)than the NDF group.The NDF group had significantly higher Acute Thrombosis and Myocardial Infarction Health Service System(ATMHSS)scores(P<0.001)and a significantly lower delayed medical treatment rate(72.38%vs 13.41%,P<0.001).BMI,duration of diabetes,plasma glucose levels,HbA1c,diabetic peripheral neuropathy,and nephropathy were all positively correlated with DF occurrence.ATMHSS scores were negatively correlated with delayed time to seek medical treatment.The logistic regression model revealed that BMI,duration of diabetes,plasma glucose levels,HbA1c,presence of diabetic peripheral neuropathy and nephropathy,ATMHSS scores,and delayed time to seek medical treatment were influencing factors for DF.ROC analysis indicated that plasma glucose levels,HbA1c,and delayed medical treatment had good predictive value with an area under the curve of 0.933 for the combined predictive model.CONCLUSION Delayed medical treatment significantly affects the probability of DF occurrence in patients with diabetes.Plasma glucose levels,HbA1c levels,and the combined predictive model of delayed medical treatment demonstrate good predictive value.
文摘Background,aim,and scope The tectonic uplift of the Cenozoic Tibetan Plateau has produced a chain effect,which is an excellent location for Earth system science research,and its uplift process,mechanism and environmental effects are the hot spot and frontier of the current research.The“Tibetan Plateau uplift-weathering-CO_(2)concentration-global climate change”model was put forward by Raymo and Ruddiman to interpret the Late Cenozoic climate change.However,there are still some questions suspended,such as does the weathering of the Tibetan Plateau have the ability to control the global climate?How to explain the modern-like global CO_(2)concentration starting at about 24 Ma?Here,a short space was taken to present a brainstorm about the above questions on account of existing geological pieces of evidence.Materials and methods In this paper,we integrate the formation and evolution of the Yangtze River and Pearl River,the origin and development of the Asian inland aridification-monsoon system,the Cenozoic tectonic uplift process of the Tibetan Plateau,and the westerly winds to discuss and analyze the relationship between the Cenozoic CO_(2)concentration changes and the uplift of the Tibetan Plateau and why the CO_(2)concentration similar to the present was formed at about 24 Ma.Results Similar correspondence of the surface uplift history of Xizang,other global mountains,and the declining CO_(2)concentration could support the theory Tibetan Plateau weathering inf luences CO_(2)concentration.Starting from 24 Ma,the most important character was the uplift and erosion of Xizang and Himalaya,collaborating with Ocean Iron Fertilization(OIF)together as an entity to control the atmospheric CO_(2)concentration because the great Asian rivers,Asian monsoons,and westerlies connected Xizang and surrounded seas together through materials transportation.Discussion Paleogeographic reconstructions from 40 Ma to 20 Ma illustrate that the main topographic change occurred in the Andes,Cordillera orogenic belt,and Xizang.We comprise a comprehensive set of evidence from independent data,which correspond temporally with the tipping point(about 24 Ma)of the atmospheric CO_(2)and we noticed that modern-like Asia monsoon,inland aridity,Asian great rivers,and climate zone formed at about 24 Ma and also there are tectonic activities for the Andes and Rockies.We raised the possibility that the modern-like atmospheric CO_(2)concentration at about 24 Ma was caused by the above geological factors.Here the rivers,monsoon,and westerlies are termed as“connectors”.In addition,these Asian rivers originated from Xizang,the monsoon,and inner Asian aridification are strongly a function of the uplift and growth of Xizang,thus,Xizang here is named as“trigger”.The distinct character of“trigger-connectors”model is that this not only takes the monsoon,westerlies,and the global great rivers into consideration but also expands the range which inf luences atmospheric CO_(2)concentration,from local points to a vast area since about 24 Ma,such as from Tibetan Plateau to Asia,including surrounded seas,after about 24 Ma.However,because the opening of the Late Oligocene-Early Miocene Antarctic periphery straits is highly coincident with the onset of modern-like global atmospheric CO_(2)concentration,we are forced to consider that they also had a significant impact on the reduction of atmospheric CO_(2)concentrations at this time.Conclusions“Trigger-connectors”was put forward to explain the Cenozoic CO_(2)variation,especially modern-like global CO_(2)concentration since about 24 Ma.Recommendations and perspectives Here we use the“trigger-connectors”model to explain the formation of modern-like CO_(2)concentrations starting at about 24 Ma,but there are still some problems.The most important premise for the“trigger-connectors”model is the constructed Cenozoic CO_(2)concentration record is reliable,which is the foundation of our hypothesis.In the future,potential improvements should focus on topographic reconstructions of Xizang and the global mountains.Here we have concentrated on Xizang in the considered timeslices but still,pay less attention to other global orogenic belts.Collaborations with geologist experts in those regions could provide valuable feedback to evaluate their potential role of them in CO_(2)evolution.What is more,considerable progress may be achieved with the addition and consideration of more and new geological data.
基金supported by the National Natural Science Foundation of China[No.U21A20334,82373544]Hebei Provincial Department of Science and Technology Centrally Guided Local Development Fund Project[236Z7705G]Occupational health risk assessment and the formulation of national occupational health standards[102393220020090000020].
文摘Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
基金supported by the Natural Science Research Project of Anhui Province University, No.2023AH040394 (to TY)Hefei Comprehensive National Science Center Leading Medicine and Frontier Technology Research Institute Project, No.2023IHM01073 (to TY)the Natural Science Foundation of Anhui Province, Nos.2308085QH258 (to JW), 2008085MH246 (to TY)。
文摘Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.
基金supported by the National Nature Science Foundation of the People’s Republic of China(No.81400225 for Zulong Sheng and No.82000382 for Yanru He)the Jiangsu Provincial Medical Youth Talent(No.QNRC2016815).
文摘Background:Myocardial infarction(MI)is known worldwide for its important disabling features,including myocarditis and cardiomyocyte apoptosis.It is believed that microRNA(miRNA)has a role in the cellular processes of apoptosis and myocarditis,and miR-219a-5p has been found to suppress the inflammatory response.However,unknown is the precise mechanism by which miR-219a-5p contributes to MI.Methods:We measured the expression of miR-219a-5p and evaluated its effects on target proteins,inflammatory factors,and apoptosis in a mouse model of MI.Echocardiography was utilized to examine the MI clinical index,and triphenyl tetrazolium chloride staining was employed to analyze the infarcted region.Enzyme-linked immunosorbent assay and Western blotting measured serum and molecular markers in heart tissues.To quantify the association with miR-219a-5p and ATPase sarcoplasmic/endoplasmic reticulum Ca^(2+)transporting 2(ATP2A2),the luciferase activity assay and Pearson’s correlation analysis were employed.Results:MiR-219a-5p exhibited low expression in a mouse model of MI,and its amplification prevented both apoptotic and inflammatory reactions.Specifically,miR-219a-5p targeted ATP2A2.Conclusion:In a mouse model of MI,miR-219a-5p exerted a potent protective effect via direct targeting of ATP2A2.