Repeatedly unidirectional bending(RUB) was applied to the magnesium alloy sheet to improve the basal texture.The effect of RUB temperature on resulting structure and room temperature properties was investigated.The te...Repeatedly unidirectional bending(RUB) was applied to the magnesium alloy sheet to improve the basal texture.The effect of RUB temperature on resulting structure and room temperature properties was investigated.The texture components of the sheet undergoing RUB at recovery temperature were similar to those of the sheet undergoing RUB at room temperature(RT).As the RUB temperature increased to above recrystallization temperature,the texture components became more disperse and the pyramidal components increased.With the increase of RUB temperature,the grain size near the surface of the sheets undergoing RUB tended to grow up.When the sheets were processed by RUB at medium-high temperature followed by annealing at 533 K,the yield strength and fracture elongation were lower than those of the cold rolled sheet;however,the Erichsen value was slightly higher than that of the cold rolled sheet.The sheet undergoing RUB at RT followed by annealing at 533 K represented the best mechanical properties.展开更多
Objective: To observe the clinical effect of Rebixiao granule (热痹消颗粒剂, RBXG) in treating repeatedly attacking acute gouty arthritis and through experimental study on blood uric acid to explore RBXG's therape...Objective: To observe the clinical effect of Rebixiao granule (热痹消颗粒剂, RBXG) in treating repeatedly attacking acute gouty arthritis and through experimental study on blood uric acid to explore RBXG's therapeutic mechanism. Methods: Ninety repeatedly attacking acute gouty arthritis patients were divided into the treated group ( n =60) and control group ( n =30). The treated group was treated with RBXG, and the control group was treated with Futalin tablets (diclofenac sodium). The baseline treatment including good rest, low purine diet, sufficient water drinking and urine alkalization, etc. was then given to both groups. Hypoxanthine 600 mg/kg and niacin 100 mg/kg was applied to hyperuricemic mice by gastrogavage to establish the animal models. Results: The clinical effective rate of the treated group was 95.0% and that of the control 90.0%. Good therapeutic effects were won, insignificant difference ( P >0.05)was shown between the two groups. However, the cure rate of the treated group was 26.7% while that of the control group was 10.0%, with significant difference ( P <0.01) shown between them. The treated group had its blood uric acid lowered, which was significantly different ( P <0.05) from that of the control group. The animal experiment indicated that all the three groups treated with different dosages of RBXG, as well as the Ash bark and Smilax glabra rhizome groups had their blood uric acid content reduced in the hyperuricemic mice. Conclusion: RBXG has a quicker initiation and better treatment effects than sole anti-inflammatory and analgesic agents on the treatment of repeatedly attacking acute gouty arthritis, showing no obvious toxic or adverse reactions and therefore good for long-term administration and likely to be a safe TCM preparation to control the symptoms and reduce the onsets of repeatedly attacking of acute gouty arthritis. The animal experiment shows that both the compound preparation and part of the single ingredients in the recipe have the function of reducing blood uric acid. However, the compound recipe has better therapeutic effects, proving to be superior to single drugs.展开更多
This research focuses on how to control the robot easily and how to generate the better trajectories of the robot with multiple joints to implement weightlifting motion. The purpose of this research is to develop a mu...This research focuses on how to control the robot easily and how to generate the better trajectories of the robot with multiple joints to implement weightlifting motion. The purpose of this research is to develop a multijoint robot can stand up successfully with an object. This research requires the operations with two items. First, when the object is lifted up slowly, the robot could stand up as easily as possible and does not tumble down. Second, the load applied on each joint should be as small as possible. In this article, a motion control method is proposed to evaluate the variations of the load torque and rotated angle of each joint with the geometrical constraints in the procedure and find the best algorithm to generate the trajectory of a weightlifting motion by a stance robot with repeatedly direct kinematics.展开更多
In the recent past,the potential benefits of wraparound geosynthetic reinforcement technique for constructing the reinforced soil foundations have been reported.This paper presents the experimental study on the behavi...In the recent past,the potential benefits of wraparound geosynthetic reinforcement technique for constructing the reinforced soil foundations have been reported.This paper presents the experimental study on the behaviour of model strip footing resting on sandy soil bed reinforced with geosynthetic in wraparound and planar forms under monotonic and repeated loadings.The geosynthetic layers were laid according to the reinforcement ratio to minimise the scale effect.It is found that for the same amount of reinforcement material,the wraparound reinforced model resulted in less settlement in comparison to planar reinforced models.The efficiency of wraparound reinforced model increased with the increase in load amplitude and the rate of total cumulative settlement substantially decreased with the increase in number of load cycles.The wraparound reinforced model has shown about 45% lower average total settlement in comparison to unreinforced model,while the double-layer reinforced model has about 41% lower average total settlement at the cost of approximately twice the material and 1.5 times the occupied land width ratio.Moreover,wraparound models have shown much greater stability in comparison to their counterpart models when subjected to incremental repeated loading.展开更多
BACKGROUND The previous studies have primarily focused on the influence of botulinum toxin A(BoNT-A)injection on emotions during the period of peak motor symptom improvement in blepharospasm patients,based on facial f...BACKGROUND The previous studies have primarily focused on the influence of botulinum toxin A(BoNT-A)injection on emotions during the period of peak motor symptom improvement in blepharospasm patients,based on facial feedback hypothesis.AIM To evaluate the sustained anxiolytic and antidepressant effects of BoNT-A in blepharospasm patients beyond motor symptom control.METHODS We recruited benign essential blepharospasm patients with BoNT-A treatment and collected their data to compare scale scores of Jankovic Rating Scale,Blepharospasm Disability Index,Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),Hamilton Anxiety Scale and Hamilton Depression Scale between pretreatment(baseline)and pre-reinjection(treatment),to further assess the effects of repeated treatments with BoNT by using sub-group analyses in the certain special states.RESULTS A total of 21 eligible blepharospasm patients were with the mean age of 58.4 years and a male-to-female ratio of 1:6.Significantly decreases in the subscale scores of SDS and SAS,including SDS well-being index,decreased capacity and hard to decide,SAS inability to sit still and headache were showed at post-a single BoNT-A injection when scale scores of Jankovic Rating Scale and Blepharospasm Disability Index were matched between baseline and posttreatment.With each additional BoNT-A injection,the odds ratio of patients with the moderate depressive symptoms decreased by 92.6%.Moreover,BoNT treatment remained a decrease in the subscale scores of SDS and SAS in patients with repeated injections.CONCLUSION This study is to demonstrate that repeated BoNT-A injection have a long-lasting relief for anxiety and depressive symptoms in blepharospasm even after its motor symptom-modulating effects have diminished.展开更多
Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we develop...Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.展开更多
Objective This study aimed to determine the temporal trends in sleep duration among Chinese adults.Methods In this series of repeated nationally representative cross-sectional surveys(China Chronic Disease and Risk Fa...Objective This study aimed to determine the temporal trends in sleep duration among Chinese adults.Methods In this series of repeated nationally representative cross-sectional surveys(China Chronic Disease and Risk Factors Surveillance)conducted between 2010 and 2018,a total of 645,420 adult participants(97,741 in 2010;175,749 in 2013;187,777 in 2015;and 184,153 in 2018)were included in the trend analysis.Linear and logistic regression models were utilized to assess trends in sleep duration.Results In 2018,the estimated overall mean sleep duration among the Chinese adult population was7.58(SD,1.45)hours per day,with no significant trend from 2010.A significant increase in short sleep duration(≤6 hours)was observed in the total population,from 15.3%(95%CI:14.1%–16.5%)in 2010 to18.5%(95%CI:17.7%–19.3%)in 2018(P<0.001).Similarly,the trend in long sleep duration(>9 hours)was also significant,increasing in weighted prevalence from 7.2%(95%CI:6.3%–8.1%)in 2010 to 9.0%(95%CI:8.2%–9.9%)in 2018(P<0.001).Conclusion The prevalence of both short and long sleep durations significantly increased among Chinese adults from 2010 to 2018,highlighting the urgency of health initiatives to promote optimal sleep duration in China.展开更多
Objective:To investigate the potential link between chromosomal polymorphisms in couples who had a medical history of idiopathic recurrent pregnancy loss.Methods:Cytogenetic investigation was conducted with mitogen(Ph...Objective:To investigate the potential link between chromosomal polymorphisms in couples who had a medical history of idiopathic recurrent pregnancy loss.Methods:Cytogenetic investigation was conducted with mitogen(Phytohemagglutinin-M,Gibco)stimulated blood T lymphocytes by Giemsa trypsin Giemsa banding and Ag-NOR banding on 580 couples with a history of idiopathic recurrent pregnancy loss and 240 couples from the general population.Thirty good chromosomal spreads were captured,karyotyped,and analyzed.The karyotypes were designated using the International System for Human Cytogenomic Nomenclature 2024.Pearson Chi-square test was used to compare the frequency of chromosomal polymorphism variations in the idiopathic recurrent pregnancy loss group with the general population group.Results:A conventional cytogenetic investigation revealed that 45.43%of couples experiencing idiopathic recurrent pregnancy loss presented with various types of chromosomal polymorphic variants,compared to 11.88%in the general population.The overall frequency of these chromosomal polymorphic variants was significantly higher in the idiopathic recurrent pregnancy loss group compared to the general population group(OR 9.97,95%CI 6.99-14.21;P<0.05).Additionally,the prevalence of polymorphic variants was higher among males(49.14%)than females(41.72%)(P=0.01).Conclusions:Chromosomal polymorphic analysis may play a crucial role in the assessment and careful clinical management of cases with idiopathic recurrent pregnancy loss,especially when no other conclusive reasons are identified during the initial evaluation.Therefore,heteromorphism should not be overlooked while investigating the causes of idiopathic recurrent pregnancy loss.展开更多
At present,there is currently a lack of unified standard methods for the determination of antimony content in groundwater in China.The precision and trueness of related detection technologies have not yet been systema...At present,there is currently a lack of unified standard methods for the determination of antimony content in groundwater in China.The precision and trueness of related detection technologies have not yet been systematically and quantitatively evaluated,which limits the effective implementation of environmental monitoring.In response to this key technical gap,this study aimed to establish a standardized method for determining antimony in groundwater using Hydride Generation–Atomic Fluorescence Spectrometry(HG-AFS).Ten laboratories participated in inter-laboratory collaborative tests,and the statistical analysis of the test data was carried out in strict accordance with the technical specifications of GB/T 6379.2—2004 and GB/T 6379.4—2006.The consistency and outliers of the data were tested by Mandel's h and k statistics,the Grubbs test and the Cochran test,and the outliers were removed to optimize the data,thereby significantly improving the reliability and accuracy.Based on the optimized data,parameters such as the repeatability limit(r),reproducibility limit(R),and method bias value(δ)were determined,and the trueness of the method was statistically evaluated.At the same time,precision-function relationships were established,and all results met the requirements.The results show that the lower the antimony content,the lower the repeatability limit(r)and reproducibility limit(R),indicating that the measurement error mainly originates from the detection limit of the method and instrument sensitivity.Therefore,improving the instrument sensitivity and reducing the detection limit are the keys to controlling the analytical error and improving precision.This study provides reliable data support and a solid technical foundation for the establishment and evaluation of standardized methods for the determination of antimony content in groundwater.展开更多
BACKGROUND Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection(MISRLR).However,limited technical guidance is available.AIM To study the utility of newly dev...BACKGROUND Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection(MISRLR).However,limited technical guidance is available.AIM To study the utility of newly developed Pringle taping method guided by liver surface in MISRLR.METHODS We retrospectively reviewed 72 cases of MISRLR performed by a single surgeon at two centers from August 2015 to July 2024.Beginning in October 2019,a liver surface-guided encirclement of hepatoduodenal ligament(LSEH)was used for repeat Pringle taping.Perioperative outcomes including Pringle taping success,operative time,blood loss,conversion rate,morbidity,and mortality were assessed.RESULTS Laparoscopic and robotic approaches were used in 63 patients and 9 patients,respectively.The median operative time,blood loss,and hospital stay were 331.5 minutes,70 mL,and 8 days,respectively.Open conversion occurred in two cases(2.8%)due to severe adhesions and right renal vein injury.Clavien-Dindo grade≥III complications occurred in 5.6%of cases with no mortality.Anti-adhesion barriers were used in 54 patients(75.0%).LSEH was attempted in 57 cases,improving Pringle taping success from 33.0%to 91.4%(P<0.001).LSEH succeeded in all patients with prior open liver resection(n=11).Among 6 patients in whom LSEH failed,3 patients(50.0%)had undergone a third liver resection,and 1 patient had a history of distal gastrectomy with choledochoduodenostomy.CONCLUSION The newly developed LSEH technique for Pringle taping in MISRLR was feasible,enhancing safety and reproducibility even in patients with a history of open liver resection.展开更多
Objective: To explore the clinical efficacy of Chinese and western integrative medicine (TCM-WM) in treating repeatedly recurrent chronic pyelonephritis (CPN) and its therapeutic mechanism.Methods: Ninety-one repeated...Objective: To explore the clinical efficacy of Chinese and western integrative medicine (TCM-WM) in treating repeatedly recurrent chronic pyelonephritis (CPN) and its therapeutic mechanism.Methods: Ninety-one repeatedly recurrent CPN patients were randomly divided into 2 groups, the control group (45 cases) treated with sufficient amount of sensitive antibiotics and other WM, the treated group (46 cases) treated with above-mentioned WM complemented with TCM syndrome differentiation (SD).Results: In the treated group completely cured was 14 cases (30.4%), markedly effective 14 cases (30.4%), the total effective rate was 91.3%; while that of the control group was 4 (8.9%), 5 (11.1%), and 48.9% respectively, (P < 0.05) and (P < 0.01); the mean days of urinary bacteria and urinary routine negative conversion were in the treated group 19.6±12.6 days and 24.3±11.5 days, obviously shorter than those of the control group (35.6±14.6 days and 53.6±16.4 days),P<0.01; the various symptoms of the treated group improved or disappeared in a short time, while in the control group a few patients improved in a longer period (P < 0.01); the various immune parameters improved in the treated group, while in the control group only IgA was elevated to some extent (P < 0.05), in comparing these data, the difference was significant (P < 0.01).Conclusion: The TCM-WM integrative treatment could obviously raise the clinical efficacy, accelerate the symptom improvement, and enhance the immune function.展开更多
On 18 November 2024,Chinese President Xi Jinping delivered a speech titled Building a Just World of Common Development at Session I of the 19th Group of 20(G20)Summit in Rio de Janeiro,Brazil.Xi Jinping has repeatedly...On 18 November 2024,Chinese President Xi Jinping delivered a speech titled Building a Just World of Common Development at Session I of the 19th Group of 20(G20)Summit in Rio de Janeiro,Brazil.Xi Jinping has repeatedly underscored the importance of promoting common development at G20 summits.Edited excerpts of his speeches on this topic since 2016 follow.展开更多
Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage se...Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.展开更多
The leucine-rich repeat(LRR)protein family is involved in a variety of fundamental metabolic and signaling processes in plants,including growth and defense responses.LRR proteins can be divided into two categories:tho...The leucine-rich repeat(LRR)protein family is involved in a variety of fundamental metabolic and signaling processes in plants,including growth and defense responses.LRR proteins can be divided into two categories:those containing LRR domains along with other structural elements,which are further subdivided into five groups,LRR receptor-like kinases,LRR receptor-like proteins,nucleotide-binding site LRR proteins,LRR-extensin proteins,and polygalacturonase-inhibiting proteins,and those containing only LRR domains.Functionally,various LRR proteins are primarily involved in plant development and responses to environmental stress.Notably,the LRR protein family plays a central role in signal transduction pathways related to stress adaptation.In this review,we classify and analyze the functions of LRR proteins in plants.While extensive research has been conducted on the roles of LRR proteins in disease resistance signaling,these proteins also play important roles in abiotic stress responses.This review highlights recent advances in understanding how LRR proteins mediate responses to biotic and abiotic stresses.Building upon these insights,further exploration of the roles of LRR proteins in abiotic stress resistance may aid efforts to develop rice varieties with enhanced stress and disease tolerance.展开更多
When microdissection testicular sperm extraction(micro-TESE)fails,a redo procedure may be the only option for patients who want a biological child.However,there are many gaps of knowledge surrounding the procedure,whi...When microdissection testicular sperm extraction(micro-TESE)fails,a redo procedure may be the only option for patients who want a biological child.However,there are many gaps of knowledge surrounding the procedure,which need to be addressed to help clinicians and patients make informed decisions.This review explores redo micro-TESE in the context of nonobstructive azoospermia(NOA).Literature was searched using Google Scholar,Medline,and PubMed.Search terms were“NOA”AND“second microdissection testicular sperm extractions”AND“redo microdissection testicles sperm extraction”AND“repeat microdissection testicular sperm extractions”AND“failed microdissection testicular sperm extractions”AND“salvage microdissection testicular sperm extractions”.Only original articles in English were included.A total of nine articles were included,consisting of four retrospective and five prospective studies.The time gap between the first and second micro-TESE varied from 6 months to 24 months.Most of the included studies reported successful surgical sperm retrieval(SSR)in the second micro-TESE in the range of 10%–21%,except in one study where it reached 42%.It has not been presented any definitive information about the use of hormonal treatment or the benefit of varicocelectomy prior to the second micro-TESE.Patients with hypospermatogenesis and Klinefelter syndrome(KS)had the highest chance of success in redo surgery.In conclusion,redo micro-TESE following a negative procedure can lead to sperm recovery in 10%–21%.Patients with hypospermatogenesis and KS have a higher chance of success.There is no enough evidence to conclude which is the best hormonal stimulation if any before a redo surgery.展开更多
The emission of anomalous X-ray pulsars(AXPs)and soft gamma-ray repeaters(SGRs)is believed to be powered by the dissipation of their strong magnetic fields,which coined the name“magnetar”.By combining timing and ene...The emission of anomalous X-ray pulsars(AXPs)and soft gamma-ray repeaters(SGRs)is believed to be powered by the dissipation of their strong magnetic fields,which coined the name“magnetar”.By combining timing and energy observational results,the magnetar model can be easily appreciated.From a timing perspective,the magnetic field strengths of AXPs and SGRs,which are calculated under the assumption of dipole radiation,are extremely strong.From an energy perspective,the X-ray/soft gamma-ray luminosities of AXPs and SGRs are larger than their rotational energy loss rates(i.e.,L_(x>E_(rot)).It is thus reasonable to assume that the high-energy radiation comes from magnetic energy decay,and the magnetar model has been extensively discussed(or accepted).However,we argue that:(ⅰ)Calculating magnetic fields by assuming that rotational energy loss is dominated by dipole radiation(i.e.,E_(rot)■E_(μ))may be controversial,and we suggest that the energies carried by outflowing particles should also be considered.(ⅱ)The fact that X-ray luminosity is greater than the rotational energy loss rate does not necessarily mean that the emission energy comes from the magnetic field decaying,which requires further observational testing.Furthermore,some observational facts conflict with the“magnetar”model,such as observations of anti-magnetars,high magnetic field pulsars,and radio and X-ray observations of AXPs/SGRs.Therefore,we propose a crusted strange star model as an alternative,which can explain many more observational facts of AXPs/SGRs.展开更多
Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating ...Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.展开更多
BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on th...BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.展开更多
In this study,we searched for dispersed repeats(DRs)in the rice(Oryza sativa)genome using the iterative procedure(IP)method.The results revealed that the O.sativa genome contained 79 DR families,comprising 992739 DNA ...In this study,we searched for dispersed repeats(DRs)in the rice(Oryza sativa)genome using the iterative procedure(IP)method.The results revealed that the O.sativa genome contained 79 DR families,comprising 992739 DNA repeats,of which 496762 and 495977 were identified on the forward and reverse DNA strands,respectively.The detected DRs were,on average,374 bp in length and occupied 66.4%of the O.sativa genome.Totally 61%of DRs,identified by the IP method,overlapped with previously annotated dispersed repeats(ADRs)detected using the Extensive De Novo TE Annotator(EDTA)pipeline.展开更多
X-ray irradiated La_(2)Ti_(2)O_(7):Pr^(3+)was found to show long-time sustainable mechanoluminescence(ML),which can realize the high sensitivity and real time detection of stress burst for more than 72 h.Under the exc...X-ray irradiated La_(2)Ti_(2)O_(7):Pr^(3+)was found to show long-time sustainable mechanoluminescence(ML),which can realize the high sensitivity and real time detection of stress burst for more than 72 h.Under the excitation of X-ray,La_(2)Ti_(2)O_(7):Pr^(3+)shows red ML emissions located at 610,624 and 638 nm,which are similar to the afterglow emission spectrum and can be ascribed to(1)^D_(2)-^(3)H_(4),^(3)P_(0)-(3)^H_(4)and (3)^P_(0)-^(3)H_(2)of Pr^(3+).And the linear increases of compressive load can induce the linear increases of ML intensity of the sample,indicating that the X-ray induced ML emission can be utilized to accurately detect the stress applied on the object.Furthermore,X-ray irradiated La_(2)Ti_(2)O_(7):Pr^(3+)possesses excellent stability and the repeatability of ML emission and the ML signals can keep stable even 50 load cycles after 1 h dacay.The thermoluminescence results suggest that abundant electrons are trapped in shallow and deep answered for stable ML emission.More importantly,the deeply trapped electrons induced ML emissions from X-ray irradiated La_(2)Ti_(2)O_(7):Pr^(3+)can be utilized to detect the stress bursts for a long time.When the sample is recharged by 5 min X-ray irradiation once,within 24 h decay,the 1500 N burst among many 1000 N cycles can be clearly detected,and the signal to noise ratio(S/N) reaches 1.32 and 1.26 after 12 and24 h decay,respectively.And even after 72 h decay,the S/N of 2500 N still arrives at 1.23 and that of4000 N reaches 1.97,indicative of long-time high sensitivity detection of abnormal stress.All these results suggest that the X-ray-irradiated La_(1.97)Ti_(2)O_(7):0.03Pr^(3+)/resin sample can realize the high sensitivity and real time detection of stress burst for more than 72 h,which thus possesses great potential application in early warning of the emergency disasters such as bridge fracture,tunnel collapse and so on.展开更多
基金Project(50504019) supported by the National Natural Science Foundation of ChinaProject(2008BB4040) supported by the Science Foundation of Chongqing, ChinaProject(2008AA4028) supported by Scientific and Technological Project of Chongqing Science and Technology Commission, China
文摘Repeatedly unidirectional bending(RUB) was applied to the magnesium alloy sheet to improve the basal texture.The effect of RUB temperature on resulting structure and room temperature properties was investigated.The texture components of the sheet undergoing RUB at recovery temperature were similar to those of the sheet undergoing RUB at room temperature(RT).As the RUB temperature increased to above recrystallization temperature,the texture components became more disperse and the pyramidal components increased.With the increase of RUB temperature,the grain size near the surface of the sheets undergoing RUB tended to grow up.When the sheets were processed by RUB at medium-high temperature followed by annealing at 533 K,the yield strength and fracture elongation were lower than those of the cold rolled sheet;however,the Erichsen value was slightly higher than that of the cold rolled sheet.The sheet undergoing RUB at RT followed by annealing at 533 K represented the best mechanical properties.
基金Supported by Project of Science and Technology Commis sion Foundation of Jiangsu Province in 1998
文摘Objective: To observe the clinical effect of Rebixiao granule (热痹消颗粒剂, RBXG) in treating repeatedly attacking acute gouty arthritis and through experimental study on blood uric acid to explore RBXG's therapeutic mechanism. Methods: Ninety repeatedly attacking acute gouty arthritis patients were divided into the treated group ( n =60) and control group ( n =30). The treated group was treated with RBXG, and the control group was treated with Futalin tablets (diclofenac sodium). The baseline treatment including good rest, low purine diet, sufficient water drinking and urine alkalization, etc. was then given to both groups. Hypoxanthine 600 mg/kg and niacin 100 mg/kg was applied to hyperuricemic mice by gastrogavage to establish the animal models. Results: The clinical effective rate of the treated group was 95.0% and that of the control 90.0%. Good therapeutic effects were won, insignificant difference ( P >0.05)was shown between the two groups. However, the cure rate of the treated group was 26.7% while that of the control group was 10.0%, with significant difference ( P <0.01) shown between them. The treated group had its blood uric acid lowered, which was significantly different ( P <0.05) from that of the control group. The animal experiment indicated that all the three groups treated with different dosages of RBXG, as well as the Ash bark and Smilax glabra rhizome groups had their blood uric acid content reduced in the hyperuricemic mice. Conclusion: RBXG has a quicker initiation and better treatment effects than sole anti-inflammatory and analgesic agents on the treatment of repeatedly attacking acute gouty arthritis, showing no obvious toxic or adverse reactions and therefore good for long-term administration and likely to be a safe TCM preparation to control the symptoms and reduce the onsets of repeatedly attacking of acute gouty arthritis. The animal experiment shows that both the compound preparation and part of the single ingredients in the recipe have the function of reducing blood uric acid. However, the compound recipe has better therapeutic effects, proving to be superior to single drugs.
文摘This research focuses on how to control the robot easily and how to generate the better trajectories of the robot with multiple joints to implement weightlifting motion. The purpose of this research is to develop a multijoint robot can stand up successfully with an object. This research requires the operations with two items. First, when the object is lifted up slowly, the robot could stand up as easily as possible and does not tumble down. Second, the load applied on each joint should be as small as possible. In this article, a motion control method is proposed to evaluate the variations of the load torque and rotated angle of each joint with the geometrical constraints in the procedure and find the best algorithm to generate the trajectory of a weightlifting motion by a stance robot with repeatedly direct kinematics.
基金funded by the Higher Education Commission(HEC),Government of the Islamic Republic of Pakistan and Edith Cowan University,Perth,Australia。
文摘In the recent past,the potential benefits of wraparound geosynthetic reinforcement technique for constructing the reinforced soil foundations have been reported.This paper presents the experimental study on the behaviour of model strip footing resting on sandy soil bed reinforced with geosynthetic in wraparound and planar forms under monotonic and repeated loadings.The geosynthetic layers were laid according to the reinforcement ratio to minimise the scale effect.It is found that for the same amount of reinforcement material,the wraparound reinforced model resulted in less settlement in comparison to planar reinforced models.The efficiency of wraparound reinforced model increased with the increase in load amplitude and the rate of total cumulative settlement substantially decreased with the increase in number of load cycles.The wraparound reinforced model has shown about 45% lower average total settlement in comparison to unreinforced model,while the double-layer reinforced model has about 41% lower average total settlement at the cost of approximately twice the material and 1.5 times the occupied land width ratio.Moreover,wraparound models have shown much greater stability in comparison to their counterpart models when subjected to incremental repeated loading.
基金Supported by the Special Funds of Jiangsu Provincial Key Research and Development Projects,No.BE2019612Scientific Research Project Cooperated by Lanzhou Biotechnology Development Co.,Ltd.+3 种基金the Key R&D Program of Jiangsu Science and Technology Project,No.BE2022049 and No.BE2022049-1National Natural Science Foundation of China,No.82171249Nanjing Rehabilitation Medicine Center ProjectJiangsu Provincial Health Commission Special Fund for Aging and Health.
文摘BACKGROUND The previous studies have primarily focused on the influence of botulinum toxin A(BoNT-A)injection on emotions during the period of peak motor symptom improvement in blepharospasm patients,based on facial feedback hypothesis.AIM To evaluate the sustained anxiolytic and antidepressant effects of BoNT-A in blepharospasm patients beyond motor symptom control.METHODS We recruited benign essential blepharospasm patients with BoNT-A treatment and collected their data to compare scale scores of Jankovic Rating Scale,Blepharospasm Disability Index,Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),Hamilton Anxiety Scale and Hamilton Depression Scale between pretreatment(baseline)and pre-reinjection(treatment),to further assess the effects of repeated treatments with BoNT by using sub-group analyses in the certain special states.RESULTS A total of 21 eligible blepharospasm patients were with the mean age of 58.4 years and a male-to-female ratio of 1:6.Significantly decreases in the subscale scores of SDS and SAS,including SDS well-being index,decreased capacity and hard to decide,SAS inability to sit still and headache were showed at post-a single BoNT-A injection when scale scores of Jankovic Rating Scale and Blepharospasm Disability Index were matched between baseline and posttreatment.With each additional BoNT-A injection,the odds ratio of patients with the moderate depressive symptoms decreased by 92.6%.Moreover,BoNT treatment remained a decrease in the subscale scores of SDS and SAS in patients with repeated injections.CONCLUSION This study is to demonstrate that repeated BoNT-A injection have a long-lasting relief for anxiety and depressive symptoms in blepharospasm even after its motor symptom-modulating effects have diminished.
基金supported partially by the Australian Government through the Australian Research Council Centres of Excellence funding scheme(project CE200100029)。
文摘Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.
基金supported by the National Natural Science Foundation of China(82341245,82371491)the Chinese Central Government(Key Project of Public Health Program)the National Key Research and Development Program of China(2018YFC1311706,2018YFC1311702)。
文摘Objective This study aimed to determine the temporal trends in sleep duration among Chinese adults.Methods In this series of repeated nationally representative cross-sectional surveys(China Chronic Disease and Risk Factors Surveillance)conducted between 2010 and 2018,a total of 645,420 adult participants(97,741 in 2010;175,749 in 2013;187,777 in 2015;and 184,153 in 2018)were included in the trend analysis.Linear and logistic regression models were utilized to assess trends in sleep duration.Results In 2018,the estimated overall mean sleep duration among the Chinese adult population was7.58(SD,1.45)hours per day,with no significant trend from 2010.A significant increase in short sleep duration(≤6 hours)was observed in the total population,from 15.3%(95%CI:14.1%–16.5%)in 2010 to18.5%(95%CI:17.7%–19.3%)in 2018(P<0.001).Similarly,the trend in long sleep duration(>9 hours)was also significant,increasing in weighted prevalence from 7.2%(95%CI:6.3%–8.1%)in 2010 to 9.0%(95%CI:8.2%–9.9%)in 2018(P<0.001).Conclusion The prevalence of both short and long sleep durations significantly increased among Chinese adults from 2010 to 2018,highlighting the urgency of health initiatives to promote optimal sleep duration in China.
基金funded by the Technology Development Board(TDB)of India's Ministry of Science and Technology(TDB/M-25/2018-19).
文摘Objective:To investigate the potential link between chromosomal polymorphisms in couples who had a medical history of idiopathic recurrent pregnancy loss.Methods:Cytogenetic investigation was conducted with mitogen(Phytohemagglutinin-M,Gibco)stimulated blood T lymphocytes by Giemsa trypsin Giemsa banding and Ag-NOR banding on 580 couples with a history of idiopathic recurrent pregnancy loss and 240 couples from the general population.Thirty good chromosomal spreads were captured,karyotyped,and analyzed.The karyotypes were designated using the International System for Human Cytogenomic Nomenclature 2024.Pearson Chi-square test was used to compare the frequency of chromosomal polymorphism variations in the idiopathic recurrent pregnancy loss group with the general population group.Results:A conventional cytogenetic investigation revealed that 45.43%of couples experiencing idiopathic recurrent pregnancy loss presented with various types of chromosomal polymorphic variants,compared to 11.88%in the general population.The overall frequency of these chromosomal polymorphic variants was significantly higher in the idiopathic recurrent pregnancy loss group compared to the general population group(OR 9.97,95%CI 6.99-14.21;P<0.05).Additionally,the prevalence of polymorphic variants was higher among males(49.14%)than females(41.72%)(P=0.01).Conclusions:Chromosomal polymorphic analysis may play a crucial role in the assessment and careful clinical management of cases with idiopathic recurrent pregnancy loss,especially when no other conclusive reasons are identified during the initial evaluation.Therefore,heteromorphism should not be overlooked while investigating the causes of idiopathic recurrent pregnancy loss.
基金supported by the National Natural Science Foundation of China(Project No.42307555).
文摘At present,there is currently a lack of unified standard methods for the determination of antimony content in groundwater in China.The precision and trueness of related detection technologies have not yet been systematically and quantitatively evaluated,which limits the effective implementation of environmental monitoring.In response to this key technical gap,this study aimed to establish a standardized method for determining antimony in groundwater using Hydride Generation–Atomic Fluorescence Spectrometry(HG-AFS).Ten laboratories participated in inter-laboratory collaborative tests,and the statistical analysis of the test data was carried out in strict accordance with the technical specifications of GB/T 6379.2—2004 and GB/T 6379.4—2006.The consistency and outliers of the data were tested by Mandel's h and k statistics,the Grubbs test and the Cochran test,and the outliers were removed to optimize the data,thereby significantly improving the reliability and accuracy.Based on the optimized data,parameters such as the repeatability limit(r),reproducibility limit(R),and method bias value(δ)were determined,and the trueness of the method was statistically evaluated.At the same time,precision-function relationships were established,and all results met the requirements.The results show that the lower the antimony content,the lower the repeatability limit(r)and reproducibility limit(R),indicating that the measurement error mainly originates from the detection limit of the method and instrument sensitivity.Therefore,improving the instrument sensitivity and reducing the detection limit are the keys to controlling the analytical error and improving precision.This study provides reliable data support and a solid technical foundation for the establishment and evaluation of standardized methods for the determination of antimony content in groundwater.
文摘BACKGROUND Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection(MISRLR).However,limited technical guidance is available.AIM To study the utility of newly developed Pringle taping method guided by liver surface in MISRLR.METHODS We retrospectively reviewed 72 cases of MISRLR performed by a single surgeon at two centers from August 2015 to July 2024.Beginning in October 2019,a liver surface-guided encirclement of hepatoduodenal ligament(LSEH)was used for repeat Pringle taping.Perioperative outcomes including Pringle taping success,operative time,blood loss,conversion rate,morbidity,and mortality were assessed.RESULTS Laparoscopic and robotic approaches were used in 63 patients and 9 patients,respectively.The median operative time,blood loss,and hospital stay were 331.5 minutes,70 mL,and 8 days,respectively.Open conversion occurred in two cases(2.8%)due to severe adhesions and right renal vein injury.Clavien-Dindo grade≥III complications occurred in 5.6%of cases with no mortality.Anti-adhesion barriers were used in 54 patients(75.0%).LSEH was attempted in 57 cases,improving Pringle taping success from 33.0%to 91.4%(P<0.001).LSEH succeeded in all patients with prior open liver resection(n=11).Among 6 patients in whom LSEH failed,3 patients(50.0%)had undergone a third liver resection,and 1 patient had a history of distal gastrectomy with choledochoduodenostomy.CONCLUSION The newly developed LSEH technique for Pringle taping in MISRLR was feasible,enhancing safety and reproducibility even in patients with a history of open liver resection.
文摘Objective: To explore the clinical efficacy of Chinese and western integrative medicine (TCM-WM) in treating repeatedly recurrent chronic pyelonephritis (CPN) and its therapeutic mechanism.Methods: Ninety-one repeatedly recurrent CPN patients were randomly divided into 2 groups, the control group (45 cases) treated with sufficient amount of sensitive antibiotics and other WM, the treated group (46 cases) treated with above-mentioned WM complemented with TCM syndrome differentiation (SD).Results: In the treated group completely cured was 14 cases (30.4%), markedly effective 14 cases (30.4%), the total effective rate was 91.3%; while that of the control group was 4 (8.9%), 5 (11.1%), and 48.9% respectively, (P < 0.05) and (P < 0.01); the mean days of urinary bacteria and urinary routine negative conversion were in the treated group 19.6±12.6 days and 24.3±11.5 days, obviously shorter than those of the control group (35.6±14.6 days and 53.6±16.4 days),P<0.01; the various symptoms of the treated group improved or disappeared in a short time, while in the control group a few patients improved in a longer period (P < 0.01); the various immune parameters improved in the treated group, while in the control group only IgA was elevated to some extent (P < 0.05), in comparing these data, the difference was significant (P < 0.01).Conclusion: The TCM-WM integrative treatment could obviously raise the clinical efficacy, accelerate the symptom improvement, and enhance the immune function.
文摘On 18 November 2024,Chinese President Xi Jinping delivered a speech titled Building a Just World of Common Development at Session I of the 19th Group of 20(G20)Summit in Rio de Janeiro,Brazil.Xi Jinping has repeatedly underscored the importance of promoting common development at G20 summits.Edited excerpts of his speeches on this topic since 2016 follow.
基金supported by the National Natural Science Foundation of China, No.61932008Natural Science Foundation of Shanghai, No.21ZR1403200 (both to JC)。
文摘Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.
基金supported by the National Natural Science Foundation of China(Grant Nos.32072048 and U2004204)National Key Research and Development Program of China(Grant No.2023YFF1001200)+2 种基金China Rice Research Institute Basal Research Fund(Grant No.CPSIBRF-CNRRI-202404)Academician Workstation of National Nanfan Research Institute(Sanya),Chinese Agricultural Academic Science(CAAS),(Grant Nos.YBXM2422 and YBXM2423)Agricultural Science and Technology Innovation Program of CAAS,China.
文摘The leucine-rich repeat(LRR)protein family is involved in a variety of fundamental metabolic and signaling processes in plants,including growth and defense responses.LRR proteins can be divided into two categories:those containing LRR domains along with other structural elements,which are further subdivided into five groups,LRR receptor-like kinases,LRR receptor-like proteins,nucleotide-binding site LRR proteins,LRR-extensin proteins,and polygalacturonase-inhibiting proteins,and those containing only LRR domains.Functionally,various LRR proteins are primarily involved in plant development and responses to environmental stress.Notably,the LRR protein family plays a central role in signal transduction pathways related to stress adaptation.In this review,we classify and analyze the functions of LRR proteins in plants.While extensive research has been conducted on the roles of LRR proteins in disease resistance signaling,these proteins also play important roles in abiotic stress responses.This review highlights recent advances in understanding how LRR proteins mediate responses to biotic and abiotic stresses.Building upon these insights,further exploration of the roles of LRR proteins in abiotic stress resistance may aid efforts to develop rice varieties with enhanced stress and disease tolerance.
文摘When microdissection testicular sperm extraction(micro-TESE)fails,a redo procedure may be the only option for patients who want a biological child.However,there are many gaps of knowledge surrounding the procedure,which need to be addressed to help clinicians and patients make informed decisions.This review explores redo micro-TESE in the context of nonobstructive azoospermia(NOA).Literature was searched using Google Scholar,Medline,and PubMed.Search terms were“NOA”AND“second microdissection testicular sperm extractions”AND“redo microdissection testicles sperm extraction”AND“repeat microdissection testicular sperm extractions”AND“failed microdissection testicular sperm extractions”AND“salvage microdissection testicular sperm extractions”.Only original articles in English were included.A total of nine articles were included,consisting of four retrospective and five prospective studies.The time gap between the first and second micro-TESE varied from 6 months to 24 months.Most of the included studies reported successful surgical sperm retrieval(SSR)in the second micro-TESE in the range of 10%–21%,except in one study where it reached 42%.It has not been presented any definitive information about the use of hormonal treatment or the benefit of varicocelectomy prior to the second micro-TESE.Patients with hypospermatogenesis and Klinefelter syndrome(KS)had the highest chance of success in redo surgery.In conclusion,redo micro-TESE following a negative procedure can lead to sperm recovery in 10%–21%.Patients with hypospermatogenesis and KS have a higher chance of success.There is no enough evidence to conclude which is the best hormonal stimulation if any before a redo surgery.
基金supported by the National Natural Science Foundation of China(12273008,12025303,12403046)the National SKA Program of China(2022SKA0130104)+3 种基金the Natural Science and Technology Foundation of Guizhou Province(QiankehejichuMS[2025]266,[2023]024,ZK[2022]304)the Foundation of Guizhou Provincial Education Department(KY(2020)003)the Academic New Seedling Fund Project of Guizhou Normal University([2022]B18)the Major Science and Technology Program of Xinjiang Uygur Autonomous Region(2022A03013-4).
文摘The emission of anomalous X-ray pulsars(AXPs)and soft gamma-ray repeaters(SGRs)is believed to be powered by the dissipation of their strong magnetic fields,which coined the name“magnetar”.By combining timing and energy observational results,the magnetar model can be easily appreciated.From a timing perspective,the magnetic field strengths of AXPs and SGRs,which are calculated under the assumption of dipole radiation,are extremely strong.From an energy perspective,the X-ray/soft gamma-ray luminosities of AXPs and SGRs are larger than their rotational energy loss rates(i.e.,L_(x>E_(rot)).It is thus reasonable to assume that the high-energy radiation comes from magnetic energy decay,and the magnetar model has been extensively discussed(or accepted).However,we argue that:(ⅰ)Calculating magnetic fields by assuming that rotational energy loss is dominated by dipole radiation(i.e.,E_(rot)■E_(μ))may be controversial,and we suggest that the energies carried by outflowing particles should also be considered.(ⅱ)The fact that X-ray luminosity is greater than the rotational energy loss rate does not necessarily mean that the emission energy comes from the magnetic field decaying,which requires further observational testing.Furthermore,some observational facts conflict with the“magnetar”model,such as observations of anti-magnetars,high magnetic field pulsars,and radio and X-ray observations of AXPs/SGRs.Therefore,we propose a crusted strange star model as an alternative,which can explain many more observational facts of AXPs/SGRs.
文摘Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.
基金Supported by National Natural Science Foundation of China,No.82160762Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Scientific Research Project,No.GXZYA20230267+2 种基金China Undergraduate Innovation and Entrepreneurship Training Program,No.S202410598060XChina Undergraduate Innovation and Entrepreneurship Training Program,No.X202410598360Future Academic Star of Guangxi Medical University,No.WLXSZX24074.
文摘BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.
基金supported by the Russian Science Foundation,Russia(Grant No.24-24-00031).
文摘In this study,we searched for dispersed repeats(DRs)in the rice(Oryza sativa)genome using the iterative procedure(IP)method.The results revealed that the O.sativa genome contained 79 DR families,comprising 992739 DNA repeats,of which 496762 and 495977 were identified on the forward and reverse DNA strands,respectively.The detected DRs were,on average,374 bp in length and occupied 66.4%of the O.sativa genome.Totally 61%of DRs,identified by the IP method,overlapped with previously annotated dispersed repeats(ADRs)detected using the Extensive De Novo TE Annotator(EDTA)pipeline.
基金Project supported by the State Key Research Projects of Shandong Natural Science Foundation (ZR2020KB019)the fund of "Two-Hundred Talent" Plan of Yantai City+1 种基金the National Natural Science Foundation of China(11974013)the Natural Science Foundation of Fujian Province (2022J011270)。
文摘X-ray irradiated La_(2)Ti_(2)O_(7):Pr^(3+)was found to show long-time sustainable mechanoluminescence(ML),which can realize the high sensitivity and real time detection of stress burst for more than 72 h.Under the excitation of X-ray,La_(2)Ti_(2)O_(7):Pr^(3+)shows red ML emissions located at 610,624 and 638 nm,which are similar to the afterglow emission spectrum and can be ascribed to(1)^D_(2)-^(3)H_(4),^(3)P_(0)-(3)^H_(4)and (3)^P_(0)-^(3)H_(2)of Pr^(3+).And the linear increases of compressive load can induce the linear increases of ML intensity of the sample,indicating that the X-ray induced ML emission can be utilized to accurately detect the stress applied on the object.Furthermore,X-ray irradiated La_(2)Ti_(2)O_(7):Pr^(3+)possesses excellent stability and the repeatability of ML emission and the ML signals can keep stable even 50 load cycles after 1 h dacay.The thermoluminescence results suggest that abundant electrons are trapped in shallow and deep answered for stable ML emission.More importantly,the deeply trapped electrons induced ML emissions from X-ray irradiated La_(2)Ti_(2)O_(7):Pr^(3+)can be utilized to detect the stress bursts for a long time.When the sample is recharged by 5 min X-ray irradiation once,within 24 h decay,the 1500 N burst among many 1000 N cycles can be clearly detected,and the signal to noise ratio(S/N) reaches 1.32 and 1.26 after 12 and24 h decay,respectively.And even after 72 h decay,the S/N of 2500 N still arrives at 1.23 and that of4000 N reaches 1.97,indicative of long-time high sensitivity detection of abnormal stress.All these results suggest that the X-ray-irradiated La_(1.97)Ti_(2)O_(7):0.03Pr^(3+)/resin sample can realize the high sensitivity and real time detection of stress burst for more than 72 h,which thus possesses great potential application in early warning of the emergency disasters such as bridge fracture,tunnel collapse and so on.
