Owls have the potential to be keystone species for conservation in fragmented landscapes, as the absence of these predators could profoundly change community structure. Yet few studies have examined how whole communit...Owls have the potential to be keystone species for conservation in fragmented landscapes, as the absence of these predators could profoundly change community structure. Yet few studies have examined how whole communities of owls respond to fragmentation, especially in the tropics. When evaluating the effect of factors related to fragmentation, such as fragment area and distance to the edge, on these birds, it is also important in heterogeneous landscapes to ask how ＇location factors＇ such as the topography, vegetation and soil of the fragment predict their persistence. In Xishuangbanna, southwest China, we established 43 transects （200 mx60 m） within 20 forest fragments to sample nocturnal birds, both visually and aurally. We used a multimodel inference approach to identify the factors that influence owl species richness, and generalized linear mixed models to predict the occurrence probabilities of each species. We found that fragmentation factors dominated location factors, with larger fragments having more species, and four of eight species were significantly more likely to occur in large fragments. Given the potential importance of these birds on regulating small mammal and other animal populations, and thus indirectly affecting seed dispersal, we suggest further protection of large f ragments and programs to increase their connectivity to the remaining smaller fragments.展开更多
We investigate the evolutions of two prominences （P1, P2） and two bundles of coronal loops （L1, L2）, observed with SDO/AIA near the east solar limb on 2012 September 22. It is found that there were large-amplitude...We investigate the evolutions of two prominences （P1, P2） and two bundles of coronal loops （L1, L2）, observed with SDO/AIA near the east solar limb on 2012 September 22. It is found that there were large-amplitude oscillations in P1 and L1 but no detectable motions in P2 and L2. These transverse oscillations were triggered by a large-scale coronal wave, originating from a large flare in a remote active region behind the solar limb. By carefully comparing the locations and heights of these oscillating and non-oscillating structures, we conclude that the propagating height of the wave is between 50 Mm and 130 Mm. The wave energy deposited in the oscillating prominence and coronal loops is at least of the order of 10-8 erg. Furthermore, local magnetic field strength and Alfv6n speeds are derived from the oscillating periods and damping time scales, which are extracted from the time series of the oscillations. It is demon- strated that oscillations can be used in not only coronal seismology, but also to reveal the properties of the wave.展开更多
Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and ery...Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among others.With this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.Methods:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro experiments.IR-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of doses.Cell counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.Results:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 cells.Celastrol downregulated glutathione peroxidase 4(GPX4)m RNA.Molecular docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by celastrol.Importantly,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 cells.Conclusion:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis inhibitors.These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.展开更多
Background:Polycystic ovary syndrome(PCOS)is the primary cause of anovulatory infertility,bringing serious harm to women’s physical and mental health.Acupuncture may be an effective treatment for PCOS.However,systema...Background:Polycystic ovary syndrome(PCOS)is the primary cause of anovulatory infertility,bringing serious harm to women’s physical and mental health.Acupuncture may be an effective treatment for PCOS.However,systematic reviews(SRs)on the efficacy and safety of acupuncture for PCOS have reported inconsistent results,and the quality of these studies has not been adequately assessed.Objective:To summarize and evaluate the current evidence on the efficacy and safety of acupuncture for PCOS,as well as to assess the quality and risks of bias of the available SRs.Search strategy:Nine electronic databases(Cochrane Library,MEDLINE,Embase,PsycINFO,CINAHL,Chinese National Knowledge Infrastructure,Wanfang Data,Chongqing VIP Chinese Science and Technology Periodical Database,and China Biology Medicine disc)were searched from their establishment to July 27,2022.Based on the principle of combining subject words with text words,the search strategy was constructed around search terms for“acupuncture,”“polycystic ovary syndrome,”and“systematic review.”Inclusion criteria:SRs of randomized controlled trials that explored the efficacy and(or)safety of acupuncture for treating patients with PCOS were included.Data extraction and analysis:Two authors independently extracted study data according to a predesigned form.Tools for evaluating the methodological quality,risk of bias,reporting quality,and confidence in study outcomes,including A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2),Risk of Bias in Systematic Reviews(ROBIS),Preferred Reporting Items for Systematic Reviews and Metaanalyses for Acupuncture(PRISMA-A),and the Grading of Recommendations Assessment,Development and Evaluation(GRADE),were used to score the included SRs.Results:A total of 885 studies were retrieved,and 11 eligible SRs were finally included in this review.The methodological quality of 2 SRs(18.18%)was low,while the other 9 SRs(81.82%)were scored as extremely low.Four SRs(36.36%)were considered to be of low risk of bias.As for reporting quality,the reporting completeness of 9 SRs(81.82%)was more than 70%.Concerning the confidence in study results,2study results were considered to have a high quality of evidence(3.13%),14(21.88%)a“moderate”quality,28(43.75%)a“low”quality,and 20(31.24%)considered a“very low”quality.Descriptive analyses suggested that combining acupuncture with other medicines can effectively improve the clinical pregnancy rate(CPR)and ovulation rate,and reduce luteinizing hormone/follicle-stimulating hormone ratio,homeostasis model assessment of insulin resistance,and body mass index(BMI).When compared with medicine alone,acupuncture alone also can improve CPR.Further,when compared with no intervention,acupuncture had a better effect in promoting the recovery of menstrual cycle and reducing BMI.Acupuncture was reported to cause no adverse events or some adverse events without serious harm.Conclusion:The efficacy and safety of acupuncture for PCOS remains uncertain due to the limitations and inconsistencies of current evidence.More high-quality studies are needed to support the use of acupuncture in PCOS.展开更多
Background:Clinical remission is the treatment target in rheumatoid arthritis (RA).This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.Methods:This study compos...Background:Clinical remission is the treatment target in rheumatoid arthritis (RA).This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.Methods:This study composed of 342 patients with RA.Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016.The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site.Subsequently,patients fulfilled remission criteria were further analyzed.The practicability of different definitions of remission of RA was rated by a panel of rheumatologists.Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.Results:In this cohort of 342 patients with RA,the proportions of patients achieving remission were 38.0%,29.5%,24.9%,21.1%,19.0%,18.1%,and 17.0%,based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP),DAS28 using ESR (DAS28-ESR),routine assessment of patient index data 3 (RAPID-3),Boolean,simplified disease activity index (SDAI),clinical disease activity index,and the newly described clinical deep remission (CliDR),respectively.Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0,respectively).Compared with the non-sustained intensive group,sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%,23.8%,and 21.3% in patients with RA based on Boolean (χ^2=3.937,P=0.047),SDAI (χ^2=4.666,P=0.031),and CliDR criteria (χ^2=4.297,P=0.038).The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide,followed by methotrexate,and hydroxychloroquine.Compared with the non-remission group,patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months,Z=-2.295,P=0.022).Conclusions:The findings in this study indicated that clinical deep remission is achievable in patients with RA.Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.展开更多
Background:Intensive therapy with disease modifying anti-rheumatic drugs(DMARDs)has been reported to improve the outcomes of rheumatoid arthritis(RA).However,real-world study on the effect of intensive therapy on RA s...Background:Intensive therapy with disease modifying anti-rheumatic drugs(DMARDs)has been reported to improve the outcomes of rheumatoid arthritis(RA).However,real-world study on the effect of intensive therapy on RA sustained remission is still lacking.This study aimed to investigate the outcome of sustained intensive DMARD therapy(SUIT)for RA in a real-world 5-year consecutive cohort.Methods:Based on a consecutive cohort of 610 out-patients with RA,remission of RA was assessed in 541 patients from 2012 to 2017,by dividing into SUIT,non-SUIT,and intermittent SUIT(Int-SUIT)groups.Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate(DAS28-ESR),28-joint disease activity score based on C-reactive protein(DAS28-CRP),and clinical deep remission criteria(CliDR).Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis.Results:The remission rates of the SUIT group decreased from 12.0%(65/541)to 5.6%(20/359)based on DAS28-ESR,from 14.0%(76/541)to 7.2%(26/359)based on DAS28-CRP,and from 8.5%(46/541)to 3.1%(11/359)based on CliDR,respectively,with a gradually decreasing trend during the 5 years.The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR(39.7%vs.19.5%,P=0.001),DAS28-CRP(42.0%vs.19.6%,P=0.001),and CliDR(24.5%vs.8.7%,P=0.001).The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR(39.7%vs.25.7%,P=0.043)and CliDR(24.5%vs.14.2%,P=0.047),but there was no significant difference between the two groups based on DAS28-CRP(42.0%vs.27.4%,P=0.066).Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions(for DAS28-ESR:odds ratio[OR],2.215,95%confidence interval[CI]:1.271–3.861,P=0.005;for DAS28-CRP:OR,1.520,95%CI:1.345–1.783,P=0.002;for CliDR:OR,1.525,95%CI:1.314–1.875,P=0.013).Conclusion:Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.展开更多
Aims Species diversity–productivity relationships in natural ecosystems have been well documented in the literature.However,biotic and abiotic factors that determine their relationships are still poorly understood,es...Aims Species diversity–productivity relationships in natural ecosystems have been well documented in the literature.However,biotic and abiotic factors that determine their relationships are still poorly understood,especially under future climate change scenarios.Methods Randomized block factorial experiments were performed in three meadows along an elevational gradient on Yulong Mountain,China,where open-top chambers and urea fertilizer manipulations were used to simulate warming and nitrogen addition,respectively.Besides species diversity,we measured functional diversity based on five traits:plant height,specific leaf area and leaf carbon,nitrogen and phosphorus contents.Several abiotic factors relating to climate(air temperature and precipitation)and soil chemistry(pH,organic carbon concentration,total nitrogen concentration and phosphorus concentration)were also measured.Generalized linear mixed-effect models were used to investigate the responses of species diversity and productivity to elevation,warming,nitrogen addition and their interactions.The effects of biotic and abiotic factors on the direction and magnitude of their relationship were also assessed.Important Findings Species diversity decreased with increasing elevation and declined under warming at mid-elevation,while productivity decreased with increasing elevation.Functional richness,maximum air temperature,soil pH and their interactions showed strong but negative influences on the species diversity–productivity relationship;the relationship shifted from positive to neutral and then to slightly negative as these sources of variation increased.Our study highlights the negative effects of short-term warming on species diversity and emphasizes the importance of both biotic and abiotic drivers of species diversity–productivity relationships in mountain meadow communities.展开更多
Background:China still suffers heavily from rabies,although reported human cases continue to decrease year over year.There are far fewer laboratory-confirmed human cases than clinically diagnosed cases,which is a big ...Background:China still suffers heavily from rabies,although reported human cases continue to decrease year over year.There are far fewer laboratory-confirmed human cases than clinically diagnosed cases,which is a big problem that needs to be addressed.In this report,we summarize analyses of all specimens from human cases tested in our laboratory over the past 15 years,in order to promote laboratory diagnosis of rabies.Methods:From 2005 to 2019,a total of 271 samples from 164 suspected rabies cases were collected from local hospitals by the local Centers for Disease Control and Prevention(CDCs)in China.Saliva,cerebrospinal fluid(CSF),serum(blood)and urine were collected for ante-mortem diagnosis,and brain tissue,neck skin tissue and cornea were collected for post-mortem diagnosis.All of the specimens were tested by reverse transcription-polymerase chain reaction(RT-PCR),and brain tissues were also tested using fluorescent antibody test(FAT).The number of positive test results obtained using different fluids or tissues,and at different stages of the disease,were compared using a chi-square test and a more effective sampling program is recommended.Results:As the national reference laboratory for rabies surveillance in China,our laboratory has tested 271 samples from 164 suspected rabies cases collected by local CDCs since 2005.We found that saliva gave the highest number of positive test results(32%),compared with CSF and other fluids.We also found that serum or blood specimens collected in the last 3 days of life can test positive by RT-PCR.Conclusions:Serum or blood samples collected in the last 3 days of a patient’s life can be used to measure viral RNA,which means that serum samples,as well as saliva and CSF,can be used to detect viral RNA for anti-mortem diagnosis of rabies.Because of our findings,we have modified our“National Surveillance Project for Human Rabies”,by adding the collection and testing of serum samples from the end of the survival period.This will improve our national surveillance and laboratory diagnosis of human rabies.展开更多
The endosomal trafficking pathways are essential for many cellular activities.They are also important targets by many intracellular pathogens.Key regulators of the endosomal trafficking include the retromer complex an...The endosomal trafficking pathways are essential for many cellular activities.They are also important targets by many intracellular pathogens.Key regulators of the endosomal trafficking include the retromer complex and sorting nexins(SNXs).Chlamydia trachomatis effector protein IncE directly targets the retromer components SNX5 and SNX6 and suppresses retromer-mediated transport,but the exact mechanism has remained unclear.We present the crystal structure of the PX domain of SNX5 in complex with IncE,showing that IncE binds to a highly conserved hydrophobic groove of SNX5.The unique helical hairpin of SNX5/6 is essential for binding,explaining the specificity of SNX5/6 for IncE.The SNX5/6–IncE interaction is required for cellular localization of IncE and its inhibitory function.Mechanistically,IncE inhibits the association of CI-MPR cargo with retromer-containing endosomal subdomains.Our study provides new insights into the regulation of retromer-mediated transport and illustrates the intricate competition between host and pathogens in controlling cellular trafficking.展开更多
Aims Phylogenetic diversity metrics can discern the relative contributions of ecological and evolutionary processes associated with the assembly of plant communities.However,the magnitude of the potential variation as...Aims Phylogenetic diversity metrics can discern the relative contributions of ecological and evolutionary processes associated with the assembly of plant communities.However,the magnitude of the potential variation associated with phylogenetic methodologies,and its effect on estimates of phylogenetic diversity,remains poorly understood.Here,we assess how sources of variation associated with estimates of phylogenetic diversity can pote ntially affect our understanding of plant community structure for a series of temperate forest plots in China.Methods In total,20 forest plots,comprising of 274 woody species and 581 herbaceous species,were surveyed and sampled along an elevational gradient of 2800 m on Taibai Mountain,China.We used multi-model inference to search for the most parsimonious relationship between estimates of phylogenetic diversity and each of four predictors(i.e.type of phylogenetic reconstruction method,phylogenetic diversity metric,woody or herbaceous growth form and elevation),and their pairwise interactions.Important Findings There was nosignificant difference in patterns of phylogenetic diversity when using synthesis-based vs.molecular-based phylogenetic methods.Results showed that elevation,the type of phylogenetic diversity metric,growth form and their interactions,accounted for>44% of the variance in our estimates of phylogenetic diversity.In general,phylogenetic diversity decreased with increasing elevation;however,the trend was weaker for herbaceous plants than for woody plants.Moreover,the three phylogenetic diversity metrics showed consistent patterns(i.e.clustered)across the elevational gradient for woody plants.For herbaceous plants,the mean pairwise distanee showed a random distribution over the gradient.These results suggest that a better understanding of temperate forest comunity structure can be obtained when estimates of phylogenetic diversity include methodological and environmental sources of variation.展开更多
Background Total gastrectomy for carcinoma in the remnant stomach(CRS)remains a technically demanding procedure.Whether robotic surgery is superior,equal,or inferior to laparoscopic surgery in patients with CRS is unc...Background Total gastrectomy for carcinoma in the remnant stomach(CRS)remains a technically demanding procedure.Whether robotic surgery is superior,equal,or inferior to laparoscopic surgery in patients with CRS is unclear.This study was designed to compare the efficacy and safety of robotic total gastrectomy(RTG)and laparoscopic total gastrectomy(LTG)for the treatment of CRS.Methods In this cohort study,we retrospectively analysed the data from patients who underwent RTG or LTG for CRS at Southwest Hospital(Chongqing,China)between May 2006 and October 2019.The surgical outcomes,post-operative complications,and survival outcomes between the two groups were compared.Results Compared with LTG,RTG was associated with similar effective operation time(272.0 vs 297.9 min,P=0.170),higher total costs(105,967.2 vs 81,629.5 RMB,P<0.001),and less estimated blood loss(229.2 vs 288.8 mL,P=0.031).No significant differences were found between the robotic and laparoscopic groups in terms of conversion rate,time to first flatus,time to first soft diet,post-operative hospital stay,post-operative complications,R0 resection rate,and number of retrieved lymph nodes(all P>0.05).The 3-year disease-free survival and 3-year overall survival rates were comparable between the two groups(65.5%vs 57.5%,P=0.918;69.0%vs 60.0%,P=0.850,respectively).Conclusions RTG is a safe and feasible procedure for the treatment of CRS and could serve as an optimal treatment for CRS.展开更多
Food intake is generally assumed to reflect a regulatory tension between homeostatic and hedonic drivers.Information from individuals with memory dysfunction suggests that episodic memory may also play a significant r...Food intake is generally assumed to reflect a regulatory tension between homeostatic and hedonic drivers.Information from individuals with memory dysfunction suggests that episodic memory may also play a significant role.We reasoned that if memory influences food intake,then disrupting a genetic factor that is important in episodic memory formation should affect food intake and energy balance.We performed spatial learning tests on neuronal specific endophilin A1(EENA1)KO mice using the four-arm baited version of the radial arms maze(RAM).Energy regulation has also been evaluated.As anticipated neuronal EENA1 KO mice had impaired spatial memory.However,loss of endophilin A1 did not result in greater food intake,or altered energy absorption efficiency,relative to wild-type(WT)mice,when fed either low or high fat diets.Moreover,loss of EENA1 did not significantly affect other features of energy balance—physical activity and energy expenditure.No statistically significant changes were observed in the expression of hypothalamic neuropeptides related to food intake regulation,or circulating levels of leptin.We conclude that food intake and energy balance are largely governed by homeostatic and hedonic processes,and when these processes are intact memory probably plays a relatively minor role in food intake regulation.展开更多
Retromer is an evolutionarily conserved multimeric protein complex that mediates intracellular transport of various vesicular cargoes and functions in a wide variety of cellular processes including polarized trafficki...Retromer is an evolutionarily conserved multimeric protein complex that mediates intracellular transport of various vesicular cargoes and functions in a wide variety of cellular processes including polarized trafficking,developmental signaling and lysosome biogenesis.Through its interaction with the Rab GTPases and their effectors,membrane lipids,molecular motors,the endocytic machinery and actin nucleation promoting factors,retromer regulates sorting and trafficking of transmembrane proteins from endosomes to the trans-Golgi network（TGN） and the plasma membrane.In this review.I highlight recent progress in the understanding of relromer-medialed protein sorting and vesicle trafficking and discuss how retromer contributes to a diverse set of developmental,physiological and pathological processes.展开更多
基金financially supported by the 1000 Plan Recruitment Program of Global Experts of China to EG
文摘Owls have the potential to be keystone species for conservation in fragmented landscapes, as the absence of these predators could profoundly change community structure. Yet few studies have examined how whole communities of owls respond to fragmentation, especially in the tropics. When evaluating the effect of factors related to fragmentation, such as fragment area and distance to the edge, on these birds, it is also important in heterogeneous landscapes to ask how ＇location factors＇ such as the topography, vegetation and soil of the fragment predict their persistence. In Xishuangbanna, southwest China, we established 43 transects （200 mx60 m） within 20 forest fragments to sample nocturnal birds, both visually and aurally. We used a multimodel inference approach to identify the factors that influence owl species richness, and generalized linear mixed models to predict the occurrence probabilities of each species. We found that fragmentation factors dominated location factors, with larger fragments having more species, and four of eight species were significantly more likely to occur in large fragments. Given the potential importance of these birds on regulating small mammal and other animal populations, and thus indirectly affecting seed dispersal, we suggest further protection of large f ragments and programs to increase their connectivity to the remaining smaller fragments.
基金supported by the National Natural Science Foundation of China (Grant Nos. 41131065, 41574165, 41421063 and 41304134)MOEC (20113402110001)+2 种基金CAS Key Research Program (KZZD-EW-01-4)the fundamental research funds for the central universities (WK2080000077)the foundation for Young Talents in College of Anhui Province (2013SQRL044ZD)
文摘We investigate the evolutions of two prominences （P1, P2） and two bundles of coronal loops （L1, L2）, observed with SDO/AIA near the east solar limb on 2012 September 22. It is found that there were large-amplitude oscillations in P1 and L1 but no detectable motions in P2 and L2. These transverse oscillations were triggered by a large-scale coronal wave, originating from a large flare in a remote active region behind the solar limb. By carefully comparing the locations and heights of these oscillating and non-oscillating structures, we conclude that the propagating height of the wave is between 50 Mm and 130 Mm. The wave energy deposited in the oscillating prominence and coronal loops is at least of the order of 10-8 erg. Furthermore, local magnetic field strength and Alfv6n speeds are derived from the oscillating periods and damping time scales, which are extracted from the time series of the oscillations. It is demon- strated that oscillations can be used in not only coronal seismology, but also to reveal the properties of the wave.
文摘Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among others.With this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.Methods:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro experiments.IR-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of doses.Cell counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.Results:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 cells.Celastrol downregulated glutathione peroxidase 4(GPX4)m RNA.Molecular docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by celastrol.Importantly,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 cells.Conclusion:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis inhibitors.These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.
基金supported by grants from the National Natural Science Foundation of China (No. 82174517)
文摘Background:Polycystic ovary syndrome(PCOS)is the primary cause of anovulatory infertility,bringing serious harm to women’s physical and mental health.Acupuncture may be an effective treatment for PCOS.However,systematic reviews(SRs)on the efficacy and safety of acupuncture for PCOS have reported inconsistent results,and the quality of these studies has not been adequately assessed.Objective:To summarize and evaluate the current evidence on the efficacy and safety of acupuncture for PCOS,as well as to assess the quality and risks of bias of the available SRs.Search strategy:Nine electronic databases(Cochrane Library,MEDLINE,Embase,PsycINFO,CINAHL,Chinese National Knowledge Infrastructure,Wanfang Data,Chongqing VIP Chinese Science and Technology Periodical Database,and China Biology Medicine disc)were searched from their establishment to July 27,2022.Based on the principle of combining subject words with text words,the search strategy was constructed around search terms for“acupuncture,”“polycystic ovary syndrome,”and“systematic review.”Inclusion criteria:SRs of randomized controlled trials that explored the efficacy and(or)safety of acupuncture for treating patients with PCOS were included.Data extraction and analysis:Two authors independently extracted study data according to a predesigned form.Tools for evaluating the methodological quality,risk of bias,reporting quality,and confidence in study outcomes,including A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2),Risk of Bias in Systematic Reviews(ROBIS),Preferred Reporting Items for Systematic Reviews and Metaanalyses for Acupuncture(PRISMA-A),and the Grading of Recommendations Assessment,Development and Evaluation(GRADE),were used to score the included SRs.Results:A total of 885 studies were retrieved,and 11 eligible SRs were finally included in this review.The methodological quality of 2 SRs(18.18%)was low,while the other 9 SRs(81.82%)were scored as extremely low.Four SRs(36.36%)were considered to be of low risk of bias.As for reporting quality,the reporting completeness of 9 SRs(81.82%)was more than 70%.Concerning the confidence in study results,2study results were considered to have a high quality of evidence(3.13%),14(21.88%)a“moderate”quality,28(43.75%)a“low”quality,and 20(31.24%)considered a“very low”quality.Descriptive analyses suggested that combining acupuncture with other medicines can effectively improve the clinical pregnancy rate(CPR)and ovulation rate,and reduce luteinizing hormone/follicle-stimulating hormone ratio,homeostasis model assessment of insulin resistance,and body mass index(BMI).When compared with medicine alone,acupuncture alone also can improve CPR.Further,when compared with no intervention,acupuncture had a better effect in promoting the recovery of menstrual cycle and reducing BMI.Acupuncture was reported to cause no adverse events or some adverse events without serious harm.Conclusion:The efficacy and safety of acupuncture for PCOS remains uncertain due to the limitations and inconsistencies of current evidence.More high-quality studies are needed to support the use of acupuncture in PCOS.
基金the grants from the National Natural Science Foundation of China (No.31530020 and No.81401329)Beijing Sci-Tech Program (No.Z171100000417007).
文摘Background:Clinical remission is the treatment target in rheumatoid arthritis (RA).This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.Methods:This study composed of 342 patients with RA.Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016.The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site.Subsequently,patients fulfilled remission criteria were further analyzed.The practicability of different definitions of remission of RA was rated by a panel of rheumatologists.Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.Results:In this cohort of 342 patients with RA,the proportions of patients achieving remission were 38.0%,29.5%,24.9%,21.1%,19.0%,18.1%,and 17.0%,based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP),DAS28 using ESR (DAS28-ESR),routine assessment of patient index data 3 (RAPID-3),Boolean,simplified disease activity index (SDAI),clinical disease activity index,and the newly described clinical deep remission (CliDR),respectively.Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0,respectively).Compared with the non-sustained intensive group,sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%,23.8%,and 21.3% in patients with RA based on Boolean (χ^2=3.937,P=0.047),SDAI (χ^2=4.666,P=0.031),and CliDR criteria (χ^2=4.297,P=0.038).The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide,followed by methotrexate,and hydroxychloroquine.Compared with the non-remission group,patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months,Z=-2.295,P=0.022).Conclusions:The findings in this study indicated that clinical deep remission is achievable in patients with RA.Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.
基金This study was supported by the grants from the National Natural Science Foundation of China(Nos.81701598 and 31240023)Beijing Municipal Science and Technology Projects(Nos.Z171100000417007 and Z191100006619110).
文摘Background:Intensive therapy with disease modifying anti-rheumatic drugs(DMARDs)has been reported to improve the outcomes of rheumatoid arthritis(RA).However,real-world study on the effect of intensive therapy on RA sustained remission is still lacking.This study aimed to investigate the outcome of sustained intensive DMARD therapy(SUIT)for RA in a real-world 5-year consecutive cohort.Methods:Based on a consecutive cohort of 610 out-patients with RA,remission of RA was assessed in 541 patients from 2012 to 2017,by dividing into SUIT,non-SUIT,and intermittent SUIT(Int-SUIT)groups.Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate(DAS28-ESR),28-joint disease activity score based on C-reactive protein(DAS28-CRP),and clinical deep remission criteria(CliDR).Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis.Results:The remission rates of the SUIT group decreased from 12.0%(65/541)to 5.6%(20/359)based on DAS28-ESR,from 14.0%(76/541)to 7.2%(26/359)based on DAS28-CRP,and from 8.5%(46/541)to 3.1%(11/359)based on CliDR,respectively,with a gradually decreasing trend during the 5 years.The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR(39.7%vs.19.5%,P=0.001),DAS28-CRP(42.0%vs.19.6%,P=0.001),and CliDR(24.5%vs.8.7%,P=0.001).The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR(39.7%vs.25.7%,P=0.043)and CliDR(24.5%vs.14.2%,P=0.047),but there was no significant difference between the two groups based on DAS28-CRP(42.0%vs.27.4%,P=0.066).Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions(for DAS28-ESR:odds ratio[OR],2.215,95%confidence interval[CI]:1.271–3.861,P=0.005;for DAS28-CRP:OR,1.520,95%CI:1.345–1.783,P=0.002;for CliDR:OR,1.525,95%CI:1.314–1.875,P=0.013).Conclusion:Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.
基金This study was financially supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB31000000)the National Natural Science Foundation of China(31500335).
文摘Aims Species diversity–productivity relationships in natural ecosystems have been well documented in the literature.However,biotic and abiotic factors that determine their relationships are still poorly understood,especially under future climate change scenarios.Methods Randomized block factorial experiments were performed in three meadows along an elevational gradient on Yulong Mountain,China,where open-top chambers and urea fertilizer manipulations were used to simulate warming and nitrogen addition,respectively.Besides species diversity,we measured functional diversity based on five traits:plant height,specific leaf area and leaf carbon,nitrogen and phosphorus contents.Several abiotic factors relating to climate(air temperature and precipitation)and soil chemistry(pH,organic carbon concentration,total nitrogen concentration and phosphorus concentration)were also measured.Generalized linear mixed-effect models were used to investigate the responses of species diversity and productivity to elevation,warming,nitrogen addition and their interactions.The effects of biotic and abiotic factors on the direction and magnitude of their relationship were also assessed.Important Findings Species diversity decreased with increasing elevation and declined under warming at mid-elevation,while productivity decreased with increasing elevation.Functional richness,maximum air temperature,soil pH and their interactions showed strong but negative influences on the species diversity–productivity relationship;the relationship shifted from positive to neutral and then to slightly negative as these sources of variation increased.Our study highlights the negative effects of short-term warming on species diversity and emphasizes the importance of both biotic and abiotic drivers of species diversity–productivity relationships in mountain meadow communities.
基金This work was supported by the National Science and Technology Major Project(2017ZX10104001,2018ZX10201002,2018ZX10713002,2018ZX10734404,2018ZX10102001)the National Program on Key Research Project of China(2016YFD0500400)+1 种基金the National Key R&D Program of China(2017YFC1200503)the Science and Technology Project of Chinese Center for Disease Control and Prevention(JY18–2-12).
文摘Background:China still suffers heavily from rabies,although reported human cases continue to decrease year over year.There are far fewer laboratory-confirmed human cases than clinically diagnosed cases,which is a big problem that needs to be addressed.In this report,we summarize analyses of all specimens from human cases tested in our laboratory over the past 15 years,in order to promote laboratory diagnosis of rabies.Methods:From 2005 to 2019,a total of 271 samples from 164 suspected rabies cases were collected from local hospitals by the local Centers for Disease Control and Prevention(CDCs)in China.Saliva,cerebrospinal fluid(CSF),serum(blood)and urine were collected for ante-mortem diagnosis,and brain tissue,neck skin tissue and cornea were collected for post-mortem diagnosis.All of the specimens were tested by reverse transcription-polymerase chain reaction(RT-PCR),and brain tissues were also tested using fluorescent antibody test(FAT).The number of positive test results obtained using different fluids or tissues,and at different stages of the disease,were compared using a chi-square test and a more effective sampling program is recommended.Results:As the national reference laboratory for rabies surveillance in China,our laboratory has tested 271 samples from 164 suspected rabies cases collected by local CDCs since 2005.We found that saliva gave the highest number of positive test results(32%),compared with CSF and other fluids.We also found that serum or blood specimens collected in the last 3 days of life can test positive by RT-PCR.Conclusions:Serum or blood samples collected in the last 3 days of a patient’s life can be used to measure viral RNA,which means that serum samples,as well as saliva and CSF,can be used to detect viral RNA for anti-mortem diagnosis of rabies.Because of our findings,we have modified our“National Surveillance Project for Human Rabies”,by adding the collection and testing of serum samples from the end of the survival period.This will improve our national surveillance and laboratory diagnosis of human rabies.
基金Research is supported by Natural Science Foundation of China(NSFC)Grants(#80502629 to QS,#31471334 to J-JL and#31671477 to DJ)DJ is a‘One Thousand Talents’program scholar,supported by Chinese Central Government and Sichuan Province.
文摘The endosomal trafficking pathways are essential for many cellular activities.They are also important targets by many intracellular pathogens.Key regulators of the endosomal trafficking include the retromer complex and sorting nexins(SNXs).Chlamydia trachomatis effector protein IncE directly targets the retromer components SNX5 and SNX6 and suppresses retromer-mediated transport,but the exact mechanism has remained unclear.We present the crystal structure of the PX domain of SNX5 in complex with IncE,showing that IncE binds to a highly conserved hydrophobic groove of SNX5.The unique helical hairpin of SNX5/6 is essential for binding,explaining the specificity of SNX5/6 for IncE.The SNX5/6–IncE interaction is required for cellular localization of IncE and its inhibitory function.Mechanistically,IncE inhibits the association of CI-MPR cargo with retromer-containing endosomal subdomains.Our study provides new insights into the regulation of retromer-mediated transport and illustrates the intricate competition between host and pathogens in controlling cellular trafficking.
基金supported by the National Natural Science Foundation of China(31500335)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB31000000).
文摘Aims Phylogenetic diversity metrics can discern the relative contributions of ecological and evolutionary processes associated with the assembly of plant communities.However,the magnitude of the potential variation associated with phylogenetic methodologies,and its effect on estimates of phylogenetic diversity,remains poorly understood.Here,we assess how sources of variation associated with estimates of phylogenetic diversity can pote ntially affect our understanding of plant community structure for a series of temperate forest plots in China.Methods In total,20 forest plots,comprising of 274 woody species and 581 herbaceous species,were surveyed and sampled along an elevational gradient of 2800 m on Taibai Mountain,China.We used multi-model inference to search for the most parsimonious relationship between estimates of phylogenetic diversity and each of four predictors(i.e.type of phylogenetic reconstruction method,phylogenetic diversity metric,woody or herbaceous growth form and elevation),and their pairwise interactions.Important Findings There was nosignificant difference in patterns of phylogenetic diversity when using synthesis-based vs.molecular-based phylogenetic methods.Results showed that elevation,the type of phylogenetic diversity metric,growth form and their interactions,accounted for>44% of the variance in our estimates of phylogenetic diversity.In general,phylogenetic diversity decreased with increasing elevation;however,the trend was weaker for herbaceous plants than for woody plants.Moreover,the three phylogenetic diversity metrics showed consistent patterns(i.e.clustered)across the elevational gradient for woody plants.For herbaceous plants,the mean pairwise distanee showed a random distribution over the gradient.These results suggest that a better understanding of temperate forest comunity structure can be obtained when estimates of phylogenetic diversity include methodological and environmental sources of variation.
文摘Background Total gastrectomy for carcinoma in the remnant stomach(CRS)remains a technically demanding procedure.Whether robotic surgery is superior,equal,or inferior to laparoscopic surgery in patients with CRS is unclear.This study was designed to compare the efficacy and safety of robotic total gastrectomy(RTG)and laparoscopic total gastrectomy(LTG)for the treatment of CRS.Methods In this cohort study,we retrospectively analysed the data from patients who underwent RTG or LTG for CRS at Southwest Hospital(Chongqing,China)between May 2006 and October 2019.The surgical outcomes,post-operative complications,and survival outcomes between the two groups were compared.Results Compared with LTG,RTG was associated with similar effective operation time(272.0 vs 297.9 min,P=0.170),higher total costs(105,967.2 vs 81,629.5 RMB,P<0.001),and less estimated blood loss(229.2 vs 288.8 mL,P=0.031).No significant differences were found between the robotic and laparoscopic groups in terms of conversion rate,time to first flatus,time to first soft diet,post-operative hospital stay,post-operative complications,R0 resection rate,and number of retrieved lymph nodes(all P>0.05).The 3-year disease-free survival and 3-year overall survival rates were comparable between the two groups(65.5%vs 57.5%,P=0.918;69.0%vs 60.0%,P=0.850,respectively).Conclusions RTG is a safe and feasible procedure for the treatment of CRS and could serve as an optimal treatment for CRS.
基金supported by funding from the National Key R&D program of China (2019YFA0801900 to JR Speakman, 2016YFA0500100 to J-J. Liu)the National Natural Science Foundation of China (92057206 to JR Speakman, 31530039 to J-J. Liu and 32070785 to Y. Yang)the Strategic Priority Research Program of Chinese Academy of Science (XDB32020100 to J-J. Liu and XDB13030100 to JR Speakman)
文摘Food intake is generally assumed to reflect a regulatory tension between homeostatic and hedonic drivers.Information from individuals with memory dysfunction suggests that episodic memory may also play a significant role.We reasoned that if memory influences food intake,then disrupting a genetic factor that is important in episodic memory formation should affect food intake and energy balance.We performed spatial learning tests on neuronal specific endophilin A1(EENA1)KO mice using the four-arm baited version of the radial arms maze(RAM).Energy regulation has also been evaluated.As anticipated neuronal EENA1 KO mice had impaired spatial memory.However,loss of endophilin A1 did not result in greater food intake,or altered energy absorption efficiency,relative to wild-type(WT)mice,when fed either low or high fat diets.Moreover,loss of EENA1 did not significantly affect other features of energy balance—physical activity and energy expenditure.No statistically significant changes were observed in the expression of hypothalamic neuropeptides related to food intake regulation,or circulating levels of leptin.We conclude that food intake and energy balance are largely governed by homeostatic and hedonic processes,and when these processes are intact memory probably plays a relatively minor role in food intake regulation.
基金supported by the National Natural Science Foundation of China(Nos.31325017,31471334 and 31530039)the National Basic Research Program(No.2014CB942802)
文摘Retromer is an evolutionarily conserved multimeric protein complex that mediates intracellular transport of various vesicular cargoes and functions in a wide variety of cellular processes including polarized trafficking,developmental signaling and lysosome biogenesis.Through its interaction with the Rab GTPases and their effectors,membrane lipids,molecular motors,the endocytic machinery and actin nucleation promoting factors,retromer regulates sorting and trafficking of transmembrane proteins from endosomes to the trans-Golgi network（TGN） and the plasma membrane.In this review.I highlight recent progress in the understanding of relromer-medialed protein sorting and vesicle trafficking and discuss how retromer contributes to a diverse set of developmental,physiological and pathological processes.
