Background:Drug-coated balloons(DCBs)are receiving increasing attention in interventional therapy for coronary artery disease.However,evidence regarding their application in acute myocardial infarction(AMI),particular...Background:Drug-coated balloons(DCBs)are receiving increasing attention in interventional therapy for coronary artery disease.However,evidence regarding their application in acute myocardial infarction(AMI),particularly in high-risk AMI patients,is limited,leading to significant clinical concerns.This study aims to compare the efficacy and safety of DCBs versus standard drug-eluting stents(DESs)in AMI patients and explore their efficacy differences in patients with ST-segment elevation myocardial infarction(STEMI),non-ST-segment elevation myocardial infarction(NSTEMI),and different risk stratifications.Methods:A single-center,retrospective cohort study was conducted,involving 86 patients who underwent percutaneous coronary intervention(PCI)for AMI between January 2023 and July 2025.Patients were divided into a DCB group(n=26)and a DES group(n=60)based on the treatment modality.According to the Killip classification of myocardial infarction at admission,patients were categorized into a low-risk group(Killip Class I,n=68)and a high-risk group(Killip Classes II-IV,n=18).The primary efficacy endpoint was targeting lesion restenosis as shown by coronary angiography follow-up(6-12 months).Safety endpoints included acute in-stent thrombosis during hospitalization(ARC criteria)and long-term coronary slow flow.A multivariate logistic regression model was used to evaluate the associations between intervention modality,risk stratification,infarction type,and endpoint events,and to test for interactions.Results:The DCB and DES groups were generally balanced in terms of baseline traditional risk factors.During hospitalization,three cases(5.0%)of acute in-stent thrombosis occurred in the DES group,all requiring urgent re-intervention,while no such events occurred in the DCB group(0%).Acute in-stent thrombosis formation was significantly associated with high-risk stratification(χ2 test,p=0.047).The overall restenosis rate was 22.1%(19/86).Multivariate analysis showed no statistically significant difference in restenosis risk between the intervention modalities(DCB vs.DES)(adjusted odds ratio[OR]=1.07,95%confidence interval[CI]0.27-4.21,p=0.920),and no statistical differences were found in subgroups based on risk stratification(p=0.382)or infarction type(p=0.484).There was a trend toward increased restenosis risk in high-risk patients(OR=12.34),but the difference was not statistically significant(95%CI 0.28-542.75,p=0.193).The incidence of long-term coronary slow flow was significantly higher in the DES group than in the DCB group(16.7%vs.3.8%,Fisher’s exact test,p=0.048),with a statistically significant difference.Conclusion:For AMI patients,DCBs demonstrate similar efficacy to DESs in preventing restenosis.However,DESs are associated with a higher risk of acute thrombosis during hospitalization,especially in high-risk patients,and a higher risk of long-term slow coronary flow.DCBs exhibit superior perioperative and long-term safety compared to DESs.Given the limited sample size,particularly the small number of high-risk patients and those treated with DCBs,the conclusions require validation through larger-scale prospective studies.展开更多
AIM:To evaluate the efficacy of the total computer vision syndrome questionnaire(CVS-Q)score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.METHODS:A...AIM:To evaluate the efficacy of the total computer vision syndrome questionnaire(CVS-Q)score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.METHODS:A total of 141 healthy computer users underwent comprehensive clinical visual function assessments,including evaluations of refractive errors,accommodation(amplitude of accommodation,positive relative accommodation,negative relative accommodation,accommodative accuracy,and accommodative facility),and vergence(phoria,positive and negative fusional vergence,near point of convergence,and vergence facility).Total CVS-Q scores were recorded to explore potential associations between symptom scores and the aforementioned clinical visual function parameters.RESULTS:The cohort included 54 males(38.3%)with a mean age of 23.9±0.58y and 87 age-matched females(61.7%)with a mean age of 23.9±0.53y.The multiple regression model was statistically significant[R²=0.60,F=13.28,degrees of freedom(DF=17122,P<0.001].This indicates that 60%of the variance in total CVS-Q scores(reflecting reported symptoms)could be explained by four clinical measurements:amplitude of accommodation,positive relative accommodation,exophoria at distance and near,and positive fusional vergence at near.CONCLUSION:The total CVS-Q score is a valid and reliable tool for predicting the presence of various nonstrabismic binocular vision anomalies and refractive errors in symptomatic computer users.展开更多
The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of ...The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.展开更多
Background:Laparoscopic anatomic hepatectomy of segment 7(LAH-S7)is a challenging surgery.In this study we aimed to investigate surgical and oncological outcomes of various approaches of LAH-S7 in patients with hepato...Background:Laparoscopic anatomic hepatectomy of segment 7(LAH-S7)is a challenging surgery.In this study we aimed to investigate surgical and oncological outcomes of various approaches of LAH-S7 in patients with hepatocellular carcinoma(HCC).A particular focus was placed on identifying the Glissonean pedicle of segment 7(G7)and the intersegmental plane.Given the scarcity of comprehensive reviews or comparative studies on clinical outcomes,we also sought to analyze the experiences and advantages associated with different approaches in relation to the anatomic variations of G7.Methods:The clinical data of 124 patients who underwent LAH-S7 for HCC across seven tertiary referral medical centers in China were retrospectively analyzed.Three surgical approaches were categorized based on the procedures used for G7 identification:the indocyanine green(ICG)fluorescence positive staining approach(IFPA),the Glissonean approach(GA),and the hepatic vein-guided approach(HVGA).Subsequently,the postoperative short-term results and oncological outcomes of the three different approaches were compared.Results:The distribution of surgical approaches among the patients was as follows:IFPA in 16(12.9%),GA in 62(50.0%),and HVGA in 46(37.1%)patients.Complications were observed in 27(21.8%)patients.The 1-,3-,and 5-year overall survival(OS)rates were 99.1%,89.2%,and 84.7%,respectively.The 1-,3-,and 5-year recurrence-free survival(RFS)rates were 99.0%,84.7%,and 69.3%,respectively.The OS and RFS rates were comparable across the three approaches.Conclusions:Following a standardized surgical procedure,LAH-S7 is demonstrated to be safe and yields favorable oncological outcomes.Surgeons performing LAH-S7 should select the appropriate surgical approach based on the anatomical characteristics and variations of G7.展开更多
Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,ven...Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infection is a prevalent disease encountered in military internal medicine and recognized as the main cause of dyspepsia,gastritis,and peptic ulcer,which are common diseases in ...BACKGROUND Helicobacter pylori(H.pylori)infection is a prevalent disease encountered in military internal medicine and recognized as the main cause of dyspepsia,gastritis,and peptic ulcer,which are common diseases in military personnel.Current guidelines in China state all patients with evidence of active infection with H.pylori are offered treatment.However,the prevalence of H.pylori infection and its regional distribution in the military population remain unclear,which hinders effective prevention and treatment strategies.Understanding the prevalence of H.pylori infection in the military population will aid in the development of customized strategies to better manage this infectious disease.AIM To investigate the prevalence of H.pylori infection in the Chinese military population in different geographic areas.METHODS This multicenter,retrospective study included 22421 individuals from five tertiary hospitals located in north,east,southwest,and northwest cities of China.H.pylori infection was identified using the urea breath test,which had been performed between January 2020 and December 2021.RESULTS Of the 22421 military service members,7416(33.1%)were urea breath test-positive.The highest prevalence of H.pylori was in the 30-39 years age group for military personnel,with an infection rate of 34.9%.The majority of infected subjects were younger than 40-years-old,accounting for 70.4%of the infected population.The individuals serviced in Lanzhou and Chengdu showed a higher infection prevalence than those in Beijing,Nanjing,and Guangzhou,with prevalence rates of 44.3%,37.9%,29.0%,31.1%,and 32.3%,respectively.CONCLUSION H.pylori infection remains a common infectious disease among military personnel in China and has a relatively high prevalence rate in northwest China.展开更多
Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarte...Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.展开更多
Mytilus contain abundant antimicrobial peptides(AMPs)that play a key role in the innate immunity.However,heterologous production of these AMPs remains challenging due to their short sequences,multiple disulfide bonds,...Mytilus contain abundant antimicrobial peptides(AMPs)that play a key role in the innate immunity.However,heterologous production of these AMPs remains challenging due to their short sequences,multiple disulfide bonds,and high content of cationic amino acids,which hinder functional expression in prokaryotic systems such as Escherichia coli.To establish a eukaryotic recombinant expression system for the AMPs of mussel and obtain recombinant mussel AMPs for subsequent studies,we reported the successful recombinant expression of myticofensin B1,a novel defensin-like AMP identified previously in Mytiluscoruscus,using the eukaryotic host Pichia pastoris.The codon-optimized gene encoding the mature myticofensin-B1(composed of 65 amino acid residues,including 6 conserved cysteine residues)was cloned into a pPICZαA vector and expressed in P.pastoris GS115.Structural fidelity of the recombinant peptide was confirmed by liquid chromatography-tandem mass spectrometry(LC-MS/MS),showing a molecular weight of 8849.9 Da,which was consistent with the theoretical prediction.Functional assays demonstrated a broad-spectrum antimicrobial activity of the recombinant myticofensin-B1,with stronger inhibition against Gram-negative bacteria.Scanning electron microscopy revealed different effects of the recombinant myticofensin-B1 against different bacteria.In addition,the recombinant myticofensin-B1 exhibited a very low hemolytic activity against sheep red blood cells and weak cytotoxicity against human A549 lung cancer cells.This study establishes P.pastoris as a powerful platform to produce functional mussel AMP and highlights the potential of the recombinant myticofensin-B1 as a therapeutic agent for aquaculture pathogens and infections.展开更多
Objective:Neoadjuvant therapy(NAT)has become the standard treatment option for patients with locally advanced breast cancer.How to non-invasively screen out patients with pathological complete response(pCR)after NAT h...Objective:Neoadjuvant therapy(NAT)has become the standard treatment option for patients with locally advanced breast cancer.How to non-invasively screen out patients with pathological complete response(pCR)after NAT has become an urgent world-wide clinical problem.Our work aims to the assessment of neoadjuvant treatment response in breast cancer patients for higher accuracy prediction using innovative artificial intelligence system.Methods:In this study,we retrospectively collected longitudinal(pre-NAT and post-NAT)multi-parametric magnetic resonance imaging(MRI)and clinicopathologic data of a total of 1,315 breast cancer patients(clinical stageⅠ-Ⅲ)who had undergone NAT followed by standard surgery and treated across 5 independent medical centers from January 2010 to January 2023.We used radiomics,3D convolutional neural network technology and clinical data statistical analysis methods to extract and screen multimodal features,and then developed and validated a Clinical-Radiomics-Deep-Learning(CRDL)model to predict patients'pCR outcomes based on multimodal fusion features.Results:We use the area under the receiver operating characteristic curve(AUC)in the primary cohort(PC)and3 external validation cohorts(VC_(1-3))to evaluate the model performance.The results showed that the AUC in the PC composed of 2 medical centers was 0.947[95%confidence interval(95%CI):0.931-0.960],and the AUC values in VC_(1-3)were 0.857(95%CI:0.810-0.901),0.883(95%CI:0.841-0.918)and 0.904(95%CI:0.860-0.941),respectively.Conclusions:The CRDL model demonstrated high accuracy and robustness in predicting pCR to NAT using multimodal fusion data.This study provides a strong foundation for non-invasive assessment of pCR status in breast cancer patients following NAT and offers critical insights to guide clinical decision-making in post-NAT treatment planning.展开更多
OBJECTIVE:To assess the efficacy and safety of the Qingyanyin formulated granules(轻燕饮配方颗粒,QYY),press needles(PN),and their combined application in addressing abdominal obesity(AO).This trial aims to offer a mor...OBJECTIVE:To assess the efficacy and safety of the Qingyanyin formulated granules(轻燕饮配方颗粒,QYY),press needles(PN),and their combined application in addressing abdominal obesity(AO).This trial aims to offer a more scientifically grounded therapeutic regimen for clinical interventions.METHODS:From March 2021 to July 2021,a multicenter,triple-blind,randomized 2×2 factorial design clinical trial was conducted across 7 centers in 4 major cities within China's mainland.The trial participants were patients diagnosed with AO.The trial followed a 1∶1∶1∶1 random allocation ratio,assigning participants to one of four groups:QYY placebo plus simulated press needles(SPN)(placebo+SPN),QYY plus SPN(QYY+SPN),QYY placebo plus PN(placebo+PN),and QYY plus PN(QYY+PN).The trial participants received treatment for 12 weeks.Observe the changes in waist circumference,body weight,body mass index(BMI),Beck Depression Inventory(BDI),Beck Anxiety Inventory(BAI)scores,and Pittsburgh Sleep Quality Index(PSQI)before and after treatment.RESULTS:The QYY+PN group exhibited significant improvements in waist circumference compared to placebo+PN[Difference=-1.59,95%CI(-3.03,-0.16)]and placebo+SPN groups[Difference=-2.01,95%CI(-3.46,-0.57)].QYY+PN demonstrated a significant advantage over placebo+SPN[Difference=-2.01,95%CI(-3.46,-0.57)],and no statistically significant interaction was observed between the two interventions(P>0.05).In terms of weight and BMI improvements,the QYY+PN,QYY+SPN,and the PN+placebo groups all experienced trending greater reductions in weight compared to the placebo group.In terms of the total scores of PSQI,BAI,and BDI,all four groups exhibited improvements compared to the baseline.Specifically,concerning the change in total PSQI scores,the QYY+PN group exhibited a greater reduction;Regarding the change in total BAI scores,the PN+placebo group demonstrated a greater decrease;As for the change in total BDI scores,the QYY+SPN group displayed a greater reduction.CONCLUSION:This study confirmed that QYY+PN can effectively reduce the waist circumference of patients with AO.Furthermore,the combined approach offers greater benefits than either treatment alone,all without any reported serious adverse events.展开更多
A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synth...A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.展开更多
Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen...Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.展开更多
Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In ...Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In this study,IR104 from Streptomyces aureocirculatus was identified from 157 wild-type imine reductases for the synthesis of(S)-2-((R)-2-oxo-4-propylpyrrolidin-1-yl)butanamide(antiepileptic drug Brivaracetam)via dynamic kinetic resolution reductive amination from ethyl 3-formylhexanoate and(S)-2-aminobutylamide with high diastereoselectivity.To further improve the catalytic efficiency of IR104,its mutant D191E/L195I/E253S/M258A(M3)was identified by saturation mutagenesis and iterative combinatorial mutagenesis,which exhibited a 102-fold increase in the catalytic efficiency relative to that of wild-type enzyme and high diastereoselectivity(98:2 d.r.).Crystal structural analysis and molecular dynamics simulations provided some insights into the molecular basis for the improved activity of the mutant enzyme.The imine reductase identified in this study could accept chiral amino amides/esters as amino donors for the dynamic kinetic resolution reductive amination of racemicα-substituted aldehydo-esters,expanding the substrate scope of imine reductases in the dynamic kinetic resolution-reductive amination.Finally,IR104-M3 was successfully used for the preparation of Brivaracetam at gram scale.Using this mutant,various N-substituted amino amides/esters with two chiral centers were also synthesized with up to 99:1 d.r.and 96%yields and subsequently converted intoγ-andδ-lactams,providing an efficient protocol for the synthesis of these important compounds via enzymatic dynamic kinetic resolution-reductive amination from simple building blocks.展开更多
A 16-channel arrayed waveguide grating(AWG)with an 800 GHz channel spacing in the O-band has been developed and fabricated based on silica planar lightwave circuit(PLC)technology.By extending the wave⁃length allocatio...A 16-channel arrayed waveguide grating(AWG)with an 800 GHz channel spacing in the O-band has been developed and fabricated based on silica planar lightwave circuit(PLC)technology.By extending the wave⁃length allocation from 8 channels to 16 channels as specified in IEEE 802.3bs,we increased the number of chan⁃nels and boosted transmission capacity to meet the 1.6 Tbps and higher-speed signal transmission requirements for future data centers.Through optimizing the AWG structure,it has achieved insertion loss(IL)better than-1.61 dB,loss uniformity below 0.35 dB,polarization-dependent loss(PDL)below 0.35 dB,adjacent channel cross⁃talk under-20.05 dB,ripple less than 0.75 dB,center wavelength offset under 0.22 nm and 1 dB bandwidth ex⁃ceeding 2.88 nm.The AWG has been successfully measured to transmit 53 Gbaud 4-level pulse amplitude modu⁃lation(PAM4)signal per channel and the total transmission speed can reach over 1.6 Tbps.展开更多
Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal deg...Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.展开更多
Background Clinical brain-computer interface(BCI)for mental disorders is an emerging interdisciplinary research field,posing new ethical concerns and challenges,yet lacking practical ethical governance guidelines for ...Background Clinical brain-computer interface(BCI)for mental disorders is an emerging interdisciplinary research field,posing new ethical concerns and challenges,yet lacking practical ethical governance guidelines for stakeholders and the entire community.Aims This study aims to establish a multidisciplinary consensus of principles for ethical governance of clinical BCI research for mental disorders and offer practical ethical guidance to stakeholders involved.Methods A systematic literature review,symposium and roundtable discussions,and a pre-Delphi(round 0)survey were conducted to form the questionnaire for the three-round modified Delphi study.Two rounds of surveys,followed by a third round of independent interviews of 25 experts from BCI-related research domains,were involved.We conducted quantitative analysis of responses and agreements among experts to reveal the consensus and differences regarding the ethical governance of mental BCI research from a multidisciplinary perspective.Results The Delphi panel emphasised important concerns of ethical review practices and ethical principles within the BCI context,identified qualified and highly influential institutions and personnel in conducting and advancing clinical BCI research,and recognised prioritised aspects in the risk-benefit evaluation.Experts expressed diverse opinions on specific ethical concerns,including concerns about invasive technology,its impact on humanity and potential social consequences.Agreement was reached that the practices of ethical governance of clinical BCI for mental disorders should focus on patient voluntariness,autonomy,long-term effects and related assessments of BCI interventions,as well as privacy protection,transparent reporting and ensuring that the research is conducted in qualified institutions with strong data security.Conclusions Ethical governance of clinical research on BCI for mental disorders should include interdisciplinary experts to balance various needs and incorporate the expertise of different stakeholders to avoid serious ethical issues.It requires scientifically grounded approaches,continuous monitoring and interdisciplinary collaboration to ensure evidence-based policies,comprehensive risk assessments and transparency,thereby promoting responsible innovations and protecting patient rights and well-being.展开更多
Objective The national lifetime prevalence of urolithiasis is estimated at 6.6%in Iran.However,reports on the composition of kidney stones have been based on imprecise methods like the chemical analysis.No prior large...Objective The national lifetime prevalence of urolithiasis is estimated at 6.6%in Iran.However,reports on the composition of kidney stones have been based on imprecise methods like the chemical analysis.No prior large-scale study has reported the composition of kidney stones based on the gold-standard methods(X-ray diffraction or infrared spectroscopy)in Iran.This study aimed to provide the composition of kidney stones based on Fourier transform infrared spectroscopy.Methods This is a cross-sectional study assessing urinary stone composition from various cities in Iran at a referral center using infrared spectroscopy from February 2019 to March 2023.Results This study determined the stone composition of 1092 patients from 10 cities in Iran.Overall,the majority of stones were composed of calcium oxalate(n=498;45.6%)and uric acid(UA,n=488;44.7%)followed by cystine(n=49;4.5%)and struvite(n=28;2.6%).Stone composition in Shiraz and Isfahan was roughly similar with a higher percentage of UA stones(53.4%and 53.6%,respectively)while the capital city of Iran(Tehran)had less frequent UA stones(39.9%)with a higher percentage of calcium oxalate stones.The percentage of UA stones increased with age as it was 11.1%in children,42.7%in adults,and 83.3%in geriatric patients(p<0.001).About 29.6%of cystine stones were observed in children.Conclusion The most frequent stone composition among kidney stones in Iran was calcium oxalate and UA stones.This relative frequency of UA stones is considerably higher than many international reports from neighboring as well as distant countries.More cystine stones were observed in children and women.Geriatric patients’stones were mostly composed of UA.展开更多
Acetolactate synthase(ALS)-targeting herbicides are among the most widely used weed-control chemicals globally.Mutations in the ALS gene can confer herbicide resistance in crops,thereby allowing selective elimination ...Acetolactate synthase(ALS)-targeting herbicides are among the most widely used weed-control chemicals globally.Mutations in the ALS gene can confer herbicide resistance in crops,thereby allowing selective elimination of weeds without harming crops.Herbicide-resistant ALS alleles were initially discovered in weeds and subsequently developed through artificial mutagenesis techniques.With the advancement of CRISPR/Cas technologies,various genome-editing tools are now available to introduce these resistant alleles,as well as novel variants,into diverse crop species.Moreover,emerging methodologies,such as directed evolution,enable the generation and screening of large populations of random ALS mutants.Consequently,ALS has become one of the most extensively targeted genes in plant gene evolution.This paper provides a comprehensive overview of both conventional and recently developed strategies for ALS evolution,with particular emphasis on CRISPR/Cas-based genome editing and directed evolution.Future perspectives on technological application are also discussed.By advancing our understanding of herbicide-resistant ALS allele development for crop improvement,these methodologies may also pave the way for their application to the evolution of other agronomically important genes.展开更多
The uplift resistance of the soil overlying shield tunnels significantly impacts their anti-floating stability.However,research on uplift resistance concerning special-shaped shield tunnels is limited.This study combi...The uplift resistance of the soil overlying shield tunnels significantly impacts their anti-floating stability.However,research on uplift resistance concerning special-shaped shield tunnels is limited.This study combines numerical simulation with machine learning techniques to explore this issue.It presents a summary of special-shaped tunnel geometries and introduces a shape coefficient.Through the finite element software,Plaxis3D,the study simulates six key parameters—shape coefficient,burial depth ratio,tunnel’s longest horizontal length,internal friction angle,cohesion,and soil submerged bulk density—that impact uplift resistance across different conditions.Employing XGBoost and ANN methods,the feature importance of each parameter was analyzed based on the numerical simulation results.The findings demonstrate that a tunnel shape more closely resembling a circle leads to reduced uplift resistance in the overlying soil,whereas other parameters exhibit the contrary effects.Furthermore,the study reveals a diminishing trend in the feature importance of buried depth ratio,internal friction angle,tunnel longest horizontal length,cohesion,soil submerged bulk density,and shape coefficient in influencing uplift resistance.展开更多
Recent years have witnessed the ever-increasing performance of Deep Neural Networks(DNNs)in computer vision tasks.However,researchers have identified a potential vulnerability:carefully crafted adversarial examples ca...Recent years have witnessed the ever-increasing performance of Deep Neural Networks(DNNs)in computer vision tasks.However,researchers have identified a potential vulnerability:carefully crafted adversarial examples can easily mislead DNNs into incorrect behavior via the injection of imperceptible modification to the input data.In this survey,we focus on(1)adversarial attack algorithms to generate adversarial examples,(2)adversarial defense techniques to secure DNNs against adversarial examples,and(3)important problems in the realm of adversarial examples beyond attack and defense,including the theoretical explanations,trade-off issues and benign attacks in adversarial examples.Additionally,we draw a brief comparison between recently published surveys on adversarial examples,and identify the future directions for the research of adversarial examples,such as the generalization of methods and the understanding of transferability,that might be solutions to the open problems in this field.展开更多
基金Social Development Science and Technology Project of Dongguan Science and Technology Bureau(Project No.:20221800905302)。
文摘Background:Drug-coated balloons(DCBs)are receiving increasing attention in interventional therapy for coronary artery disease.However,evidence regarding their application in acute myocardial infarction(AMI),particularly in high-risk AMI patients,is limited,leading to significant clinical concerns.This study aims to compare the efficacy and safety of DCBs versus standard drug-eluting stents(DESs)in AMI patients and explore their efficacy differences in patients with ST-segment elevation myocardial infarction(STEMI),non-ST-segment elevation myocardial infarction(NSTEMI),and different risk stratifications.Methods:A single-center,retrospective cohort study was conducted,involving 86 patients who underwent percutaneous coronary intervention(PCI)for AMI between January 2023 and July 2025.Patients were divided into a DCB group(n=26)and a DES group(n=60)based on the treatment modality.According to the Killip classification of myocardial infarction at admission,patients were categorized into a low-risk group(Killip Class I,n=68)and a high-risk group(Killip Classes II-IV,n=18).The primary efficacy endpoint was targeting lesion restenosis as shown by coronary angiography follow-up(6-12 months).Safety endpoints included acute in-stent thrombosis during hospitalization(ARC criteria)and long-term coronary slow flow.A multivariate logistic regression model was used to evaluate the associations between intervention modality,risk stratification,infarction type,and endpoint events,and to test for interactions.Results:The DCB and DES groups were generally balanced in terms of baseline traditional risk factors.During hospitalization,three cases(5.0%)of acute in-stent thrombosis occurred in the DES group,all requiring urgent re-intervention,while no such events occurred in the DCB group(0%).Acute in-stent thrombosis formation was significantly associated with high-risk stratification(χ2 test,p=0.047).The overall restenosis rate was 22.1%(19/86).Multivariate analysis showed no statistically significant difference in restenosis risk between the intervention modalities(DCB vs.DES)(adjusted odds ratio[OR]=1.07,95%confidence interval[CI]0.27-4.21,p=0.920),and no statistical differences were found in subgroups based on risk stratification(p=0.382)or infarction type(p=0.484).There was a trend toward increased restenosis risk in high-risk patients(OR=12.34),but the difference was not statistically significant(95%CI 0.28-542.75,p=0.193).The incidence of long-term coronary slow flow was significantly higher in the DES group than in the DCB group(16.7%vs.3.8%,Fisher’s exact test,p=0.048),with a statistically significant difference.Conclusion:For AMI patients,DCBs demonstrate similar efficacy to DESs in preventing restenosis.However,DESs are associated with a higher risk of acute thrombosis during hospitalization,especially in high-risk patients,and a higher risk of long-term slow coronary flow.DCBs exhibit superior perioperative and long-term safety compared to DESs.Given the limited sample size,particularly the small number of high-risk patients and those treated with DCBs,the conclusions require validation through larger-scale prospective studies.
基金Supported by Ongoing Research Funding Program(ORFFT-2025-054-1),King Saud University,Riyadh,Saudi Arabia.
文摘AIM:To evaluate the efficacy of the total computer vision syndrome questionnaire(CVS-Q)score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.METHODS:A total of 141 healthy computer users underwent comprehensive clinical visual function assessments,including evaluations of refractive errors,accommodation(amplitude of accommodation,positive relative accommodation,negative relative accommodation,accommodative accuracy,and accommodative facility),and vergence(phoria,positive and negative fusional vergence,near point of convergence,and vergence facility).Total CVS-Q scores were recorded to explore potential associations between symptom scores and the aforementioned clinical visual function parameters.RESULTS:The cohort included 54 males(38.3%)with a mean age of 23.9±0.58y and 87 age-matched females(61.7%)with a mean age of 23.9±0.53y.The multiple regression model was statistically significant[R²=0.60,F=13.28,degrees of freedom(DF=17122,P<0.001].This indicates that 60%of the variance in total CVS-Q scores(reflecting reported symptoms)could be explained by four clinical measurements:amplitude of accommodation,positive relative accommodation,exophoria at distance and near,and positive fusional vergence at near.CONCLUSION:The total CVS-Q score is a valid and reliable tool for predicting the presence of various nonstrabismic binocular vision anomalies and refractive errors in symptomatic computer users.
基金supported by the National Natural Science Foundation of China(81760037)Yunling Scholar Project of Yunnan Province(YNWR-YLXZ-2019-0005)+1 种基金Hunan Provincial Innovation Platform and Talent Program(2018SK4004)Hunan Provincial Natural Science Foundation(2019JJ80048).
文摘The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.
基金supported by grants from the Scientific Research Fund of Education Department of Yunnan Province(2023J767)the National Natural Science Foundation of China(82272963 and 82472718)+6 种基金Health Research Project of Hunan Provincial Health Commission(W20242019)Hunan Provincial Health High-Level Talent Scientific Research Project(R2023096)Hunan Provincial Department of Science and Technology Health Industry Joint Fund(2024JJ9479)Guangdong Province Basic and Applied Basic Research Foundation Project-Guangdong Province Natural Science Foundation(2024A1515220154)"Leading Goose"Project of the Science and Technology Department of Zhejiang Province(2024C03049)Major Project of Health Science and Technology Program of Zhejiang Province(WKJ-ZJ-2407)the National Key Research and Development Program(2024YFB331170204).
文摘Background:Laparoscopic anatomic hepatectomy of segment 7(LAH-S7)is a challenging surgery.In this study we aimed to investigate surgical and oncological outcomes of various approaches of LAH-S7 in patients with hepatocellular carcinoma(HCC).A particular focus was placed on identifying the Glissonean pedicle of segment 7(G7)and the intersegmental plane.Given the scarcity of comprehensive reviews or comparative studies on clinical outcomes,we also sought to analyze the experiences and advantages associated with different approaches in relation to the anatomic variations of G7.Methods:The clinical data of 124 patients who underwent LAH-S7 for HCC across seven tertiary referral medical centers in China were retrospectively analyzed.Three surgical approaches were categorized based on the procedures used for G7 identification:the indocyanine green(ICG)fluorescence positive staining approach(IFPA),the Glissonean approach(GA),and the hepatic vein-guided approach(HVGA).Subsequently,the postoperative short-term results and oncological outcomes of the three different approaches were compared.Results:The distribution of surgical approaches among the patients was as follows:IFPA in 16(12.9%),GA in 62(50.0%),and HVGA in 46(37.1%)patients.Complications were observed in 27(21.8%)patients.The 1-,3-,and 5-year overall survival(OS)rates were 99.1%,89.2%,and 84.7%,respectively.The 1-,3-,and 5-year recurrence-free survival(RFS)rates were 99.0%,84.7%,and 69.3%,respectively.The OS and RFS rates were comparable across the three approaches.Conclusions:Following a standardized surgical procedure,LAH-S7 is demonstrated to be safe and yields favorable oncological outcomes.Surgeons performing LAH-S7 should select the appropriate surgical approach based on the anatomical characteristics and variations of G7.
基金supported by the Beijing Natural Science Foundation(No.Z230016)the National Key Research and Development Program of China(No.2022YFC 2502606)+4 种基金the Major Program of the National Natural Science Foundation of China(No.82293630)the Peking University Medicine Fund for the World’s Leading Discipline or Discipline Cluster Development(No.71003Y3035)the Plan Project of Tongzhou Municipal Science and Technology(No.KJ2024CX045)the National Natural Science Foundation of China(No.82170208)the Fundamental Research Funds for the Central Universities。
文摘Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is a prevalent disease encountered in military internal medicine and recognized as the main cause of dyspepsia,gastritis,and peptic ulcer,which are common diseases in military personnel.Current guidelines in China state all patients with evidence of active infection with H.pylori are offered treatment.However,the prevalence of H.pylori infection and its regional distribution in the military population remain unclear,which hinders effective prevention and treatment strategies.Understanding the prevalence of H.pylori infection in the military population will aid in the development of customized strategies to better manage this infectious disease.AIM To investigate the prevalence of H.pylori infection in the Chinese military population in different geographic areas.METHODS This multicenter,retrospective study included 22421 individuals from five tertiary hospitals located in north,east,southwest,and northwest cities of China.H.pylori infection was identified using the urea breath test,which had been performed between January 2020 and December 2021.RESULTS Of the 22421 military service members,7416(33.1%)were urea breath test-positive.The highest prevalence of H.pylori was in the 30-39 years age group for military personnel,with an infection rate of 34.9%.The majority of infected subjects were younger than 40-years-old,accounting for 70.4%of the infected population.The individuals serviced in Lanzhou and Chengdu showed a higher infection prevalence than those in Beijing,Nanjing,and Guangzhou,with prevalence rates of 44.3%,37.9%,29.0%,31.1%,and 32.3%,respectively.CONCLUSION H.pylori infection remains a common infectious disease among military personnel in China and has a relatively high prevalence rate in northwest China.
基金supported by grants from the National Natural Science Foundation of China(91959203,82272836 and 82373017)。
文摘Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.
基金supported by the National Natural Science Foundation of China(32271580,42020104009)the Fundamental Research Funds for Zhejiang Provincial Universities and Research Institutes(JX6311101923)。
文摘Mytilus contain abundant antimicrobial peptides(AMPs)that play a key role in the innate immunity.However,heterologous production of these AMPs remains challenging due to their short sequences,multiple disulfide bonds,and high content of cationic amino acids,which hinder functional expression in prokaryotic systems such as Escherichia coli.To establish a eukaryotic recombinant expression system for the AMPs of mussel and obtain recombinant mussel AMPs for subsequent studies,we reported the successful recombinant expression of myticofensin B1,a novel defensin-like AMP identified previously in Mytiluscoruscus,using the eukaryotic host Pichia pastoris.The codon-optimized gene encoding the mature myticofensin-B1(composed of 65 amino acid residues,including 6 conserved cysteine residues)was cloned into a pPICZαA vector and expressed in P.pastoris GS115.Structural fidelity of the recombinant peptide was confirmed by liquid chromatography-tandem mass spectrometry(LC-MS/MS),showing a molecular weight of 8849.9 Da,which was consistent with the theoretical prediction.Functional assays demonstrated a broad-spectrum antimicrobial activity of the recombinant myticofensin-B1,with stronger inhibition against Gram-negative bacteria.Scanning electron microscopy revealed different effects of the recombinant myticofensin-B1 against different bacteria.In addition,the recombinant myticofensin-B1 exhibited a very low hemolytic activity against sheep red blood cells and weak cytotoxicity against human A549 lung cancer cells.This study establishes P.pastoris as a powerful platform to produce functional mussel AMP and highlights the potential of the recombinant myticofensin-B1 as a therapeutic agent for aquaculture pathogens and infections.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2023-JKCS-23)the Special Research Fund for Central Universities,Peking Union Medical College[No.2022-I2M-C&T-A-014,CAMS Innovation Fund for Medical Sciences(CIFMS)]。
文摘Objective:Neoadjuvant therapy(NAT)has become the standard treatment option for patients with locally advanced breast cancer.How to non-invasively screen out patients with pathological complete response(pCR)after NAT has become an urgent world-wide clinical problem.Our work aims to the assessment of neoadjuvant treatment response in breast cancer patients for higher accuracy prediction using innovative artificial intelligence system.Methods:In this study,we retrospectively collected longitudinal(pre-NAT and post-NAT)multi-parametric magnetic resonance imaging(MRI)and clinicopathologic data of a total of 1,315 breast cancer patients(clinical stageⅠ-Ⅲ)who had undergone NAT followed by standard surgery and treated across 5 independent medical centers from January 2010 to January 2023.We used radiomics,3D convolutional neural network technology and clinical data statistical analysis methods to extract and screen multimodal features,and then developed and validated a Clinical-Radiomics-Deep-Learning(CRDL)model to predict patients'pCR outcomes based on multimodal fusion features.Results:We use the area under the receiver operating characteristic curve(AUC)in the primary cohort(PC)and3 external validation cohorts(VC_(1-3))to evaluate the model performance.The results showed that the AUC in the PC composed of 2 medical centers was 0.947[95%confidence interval(95%CI):0.931-0.960],and the AUC values in VC_(1-3)were 0.857(95%CI:0.810-0.901),0.883(95%CI:0.841-0.918)and 0.904(95%CI:0.860-0.941),respectively.Conclusions:The CRDL model demonstrated high accuracy and robustness in predicting pCR to NAT using multimodal fusion data.This study provides a strong foundation for non-invasive assessment of pCR status in breast cancer patients following NAT and offers critical insights to guide clinical decision-making in post-NAT treatment planning.
基金National Key Research and Development Project:Clinical Evaluation of the Interventional Techniques for Abdominal Obesity(No.2019YFC1710102)。
文摘OBJECTIVE:To assess the efficacy and safety of the Qingyanyin formulated granules(轻燕饮配方颗粒,QYY),press needles(PN),and their combined application in addressing abdominal obesity(AO).This trial aims to offer a more scientifically grounded therapeutic regimen for clinical interventions.METHODS:From March 2021 to July 2021,a multicenter,triple-blind,randomized 2×2 factorial design clinical trial was conducted across 7 centers in 4 major cities within China's mainland.The trial participants were patients diagnosed with AO.The trial followed a 1∶1∶1∶1 random allocation ratio,assigning participants to one of four groups:QYY placebo plus simulated press needles(SPN)(placebo+SPN),QYY plus SPN(QYY+SPN),QYY placebo plus PN(placebo+PN),and QYY plus PN(QYY+PN).The trial participants received treatment for 12 weeks.Observe the changes in waist circumference,body weight,body mass index(BMI),Beck Depression Inventory(BDI),Beck Anxiety Inventory(BAI)scores,and Pittsburgh Sleep Quality Index(PSQI)before and after treatment.RESULTS:The QYY+PN group exhibited significant improvements in waist circumference compared to placebo+PN[Difference=-1.59,95%CI(-3.03,-0.16)]and placebo+SPN groups[Difference=-2.01,95%CI(-3.46,-0.57)].QYY+PN demonstrated a significant advantage over placebo+SPN[Difference=-2.01,95%CI(-3.46,-0.57)],and no statistically significant interaction was observed between the two interventions(P>0.05).In terms of weight and BMI improvements,the QYY+PN,QYY+SPN,and the PN+placebo groups all experienced trending greater reductions in weight compared to the placebo group.In terms of the total scores of PSQI,BAI,and BDI,all four groups exhibited improvements compared to the baseline.Specifically,concerning the change in total PSQI scores,the QYY+PN group exhibited a greater reduction;Regarding the change in total BAI scores,the PN+placebo group demonstrated a greater decrease;As for the change in total BDI scores,the QYY+SPN group displayed a greater reduction.CONCLUSION:This study confirmed that QYY+PN can effectively reduce the waist circumference of patients with AO.Furthermore,the combined approach offers greater benefits than either treatment alone,all without any reported serious adverse events.
基金supported by grants from the Guangxi Science and Technology Major Project(GKAA24206023)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Natural Science Foundation of China(32272120)the National Key Research and Development Program of China(2024YFF1000800)the Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops Major Project(FCBRCE-202502,FCBRCE-202504).
文摘A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.
基金supported by the National Natural Science Foundation of China,Nos.82171387 and 31830111(both to SL).
文摘Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.
文摘Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In this study,IR104 from Streptomyces aureocirculatus was identified from 157 wild-type imine reductases for the synthesis of(S)-2-((R)-2-oxo-4-propylpyrrolidin-1-yl)butanamide(antiepileptic drug Brivaracetam)via dynamic kinetic resolution reductive amination from ethyl 3-formylhexanoate and(S)-2-aminobutylamide with high diastereoselectivity.To further improve the catalytic efficiency of IR104,its mutant D191E/L195I/E253S/M258A(M3)was identified by saturation mutagenesis and iterative combinatorial mutagenesis,which exhibited a 102-fold increase in the catalytic efficiency relative to that of wild-type enzyme and high diastereoselectivity(98:2 d.r.).Crystal structural analysis and molecular dynamics simulations provided some insights into the molecular basis for the improved activity of the mutant enzyme.The imine reductase identified in this study could accept chiral amino amides/esters as amino donors for the dynamic kinetic resolution reductive amination of racemicα-substituted aldehydo-esters,expanding the substrate scope of imine reductases in the dynamic kinetic resolution-reductive amination.Finally,IR104-M3 was successfully used for the preparation of Brivaracetam at gram scale.Using this mutant,various N-substituted amino amides/esters with two chiral centers were also synthesized with up to 99:1 d.r.and 96%yields and subsequently converted intoγ-andδ-lactams,providing an efficient protocol for the synthesis of these important compounds via enzymatic dynamic kinetic resolution-reductive amination from simple building blocks.
基金Supported by the National Key Research and Development Program of China(2021YFB2800201)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB43000000)。
文摘A 16-channel arrayed waveguide grating(AWG)with an 800 GHz channel spacing in the O-band has been developed and fabricated based on silica planar lightwave circuit(PLC)technology.By extending the wave⁃length allocation from 8 channels to 16 channels as specified in IEEE 802.3bs,we increased the number of chan⁃nels and boosted transmission capacity to meet the 1.6 Tbps and higher-speed signal transmission requirements for future data centers.Through optimizing the AWG structure,it has achieved insertion loss(IL)better than-1.61 dB,loss uniformity below 0.35 dB,polarization-dependent loss(PDL)below 0.35 dB,adjacent channel cross⁃talk under-20.05 dB,ripple less than 0.75 dB,center wavelength offset under 0.22 nm and 1 dB bandwidth ex⁃ceeding 2.88 nm.The AWG has been successfully measured to transmit 53 Gbaud 4-level pulse amplitude modu⁃lation(PAM4)signal per channel and the total transmission speed can reach over 1.6 Tbps.
基金supported by the National Natural Science Foundation of China,Nos.82171076(to XS)and U22A20311(to XS),82101168(to TL)Shanghai Science and technology Innovation Action Plan,No.23Y11901300(to JS)+1 种基金Science and Technology Commission of Shanghai Municipality,No.21ZR1451500(to TL)Shanghai Pujiang Program,No.22PJ1412200(to BY)。
文摘Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.
基金funded by the Shanghai Philosophy and Social Science Planning Project (2021BZX008)the National Social Science Foundation of China (23BZX110)the National Office for Philosophy and Social Science (20&ZD045).
文摘Background Clinical brain-computer interface(BCI)for mental disorders is an emerging interdisciplinary research field,posing new ethical concerns and challenges,yet lacking practical ethical governance guidelines for stakeholders and the entire community.Aims This study aims to establish a multidisciplinary consensus of principles for ethical governance of clinical BCI research for mental disorders and offer practical ethical guidance to stakeholders involved.Methods A systematic literature review,symposium and roundtable discussions,and a pre-Delphi(round 0)survey were conducted to form the questionnaire for the three-round modified Delphi study.Two rounds of surveys,followed by a third round of independent interviews of 25 experts from BCI-related research domains,were involved.We conducted quantitative analysis of responses and agreements among experts to reveal the consensus and differences regarding the ethical governance of mental BCI research from a multidisciplinary perspective.Results The Delphi panel emphasised important concerns of ethical review practices and ethical principles within the BCI context,identified qualified and highly influential institutions and personnel in conducting and advancing clinical BCI research,and recognised prioritised aspects in the risk-benefit evaluation.Experts expressed diverse opinions on specific ethical concerns,including concerns about invasive technology,its impact on humanity and potential social consequences.Agreement was reached that the practices of ethical governance of clinical BCI for mental disorders should focus on patient voluntariness,autonomy,long-term effects and related assessments of BCI interventions,as well as privacy protection,transparent reporting and ensuring that the research is conducted in qualified institutions with strong data security.Conclusions Ethical governance of clinical research on BCI for mental disorders should include interdisciplinary experts to balance various needs and incorporate the expertise of different stakeholders to avoid serious ethical issues.It requires scientifically grounded approaches,continuous monitoring and interdisciplinary collaboration to ensure evidence-based policies,comprehensive risk assessments and transparency,thereby promoting responsible innovations and protecting patient rights and well-being.
文摘Objective The national lifetime prevalence of urolithiasis is estimated at 6.6%in Iran.However,reports on the composition of kidney stones have been based on imprecise methods like the chemical analysis.No prior large-scale study has reported the composition of kidney stones based on the gold-standard methods(X-ray diffraction or infrared spectroscopy)in Iran.This study aimed to provide the composition of kidney stones based on Fourier transform infrared spectroscopy.Methods This is a cross-sectional study assessing urinary stone composition from various cities in Iran at a referral center using infrared spectroscopy from February 2019 to March 2023.Results This study determined the stone composition of 1092 patients from 10 cities in Iran.Overall,the majority of stones were composed of calcium oxalate(n=498;45.6%)and uric acid(UA,n=488;44.7%)followed by cystine(n=49;4.5%)and struvite(n=28;2.6%).Stone composition in Shiraz and Isfahan was roughly similar with a higher percentage of UA stones(53.4%and 53.6%,respectively)while the capital city of Iran(Tehran)had less frequent UA stones(39.9%)with a higher percentage of calcium oxalate stones.The percentage of UA stones increased with age as it was 11.1%in children,42.7%in adults,and 83.3%in geriatric patients(p<0.001).About 29.6%of cystine stones were observed in children.Conclusion The most frequent stone composition among kidney stones in Iran was calcium oxalate and UA stones.This relative frequency of UA stones is considerably higher than many international reports from neighboring as well as distant countries.More cystine stones were observed in children and women.Geriatric patients’stones were mostly composed of UA.
基金Guangdong Basic and Applied Basic Research Foundation(2023B1515120050,2023A1515110529 and 2024A1515012454)Shenzhen Science and Technology Program(JCYJ20230807145759008 and KJZD20240903100206009).
文摘Acetolactate synthase(ALS)-targeting herbicides are among the most widely used weed-control chemicals globally.Mutations in the ALS gene can confer herbicide resistance in crops,thereby allowing selective elimination of weeds without harming crops.Herbicide-resistant ALS alleles were initially discovered in weeds and subsequently developed through artificial mutagenesis techniques.With the advancement of CRISPR/Cas technologies,various genome-editing tools are now available to introduce these resistant alleles,as well as novel variants,into diverse crop species.Moreover,emerging methodologies,such as directed evolution,enable the generation and screening of large populations of random ALS mutants.Consequently,ALS has become one of the most extensively targeted genes in plant gene evolution.This paper provides a comprehensive overview of both conventional and recently developed strategies for ALS evolution,with particular emphasis on CRISPR/Cas-based genome editing and directed evolution.Future perspectives on technological application are also discussed.By advancing our understanding of herbicide-resistant ALS allele development for crop improvement,these methodologies may also pave the way for their application to the evolution of other agronomically important genes.
基金Guangzhou Metro Scientific Research Project(No.JT204-100111-23001)Chongqing Municipal Special Project for Technological Innovation and Application Development(No.CSTB2022TIAD-KPX0101)Science and Technology Research and Development Program of China State Railway Group Co.,Ltd.(No.N2023G045)。
文摘The uplift resistance of the soil overlying shield tunnels significantly impacts their anti-floating stability.However,research on uplift resistance concerning special-shaped shield tunnels is limited.This study combines numerical simulation with machine learning techniques to explore this issue.It presents a summary of special-shaped tunnel geometries and introduces a shape coefficient.Through the finite element software,Plaxis3D,the study simulates six key parameters—shape coefficient,burial depth ratio,tunnel’s longest horizontal length,internal friction angle,cohesion,and soil submerged bulk density—that impact uplift resistance across different conditions.Employing XGBoost and ANN methods,the feature importance of each parameter was analyzed based on the numerical simulation results.The findings demonstrate that a tunnel shape more closely resembling a circle leads to reduced uplift resistance in the overlying soil,whereas other parameters exhibit the contrary effects.Furthermore,the study reveals a diminishing trend in the feature importance of buried depth ratio,internal friction angle,tunnel longest horizontal length,cohesion,soil submerged bulk density,and shape coefficient in influencing uplift resistance.
基金Supported by the National Natural Science Foundation of China(U1903214,62372339,62371350,61876135)the Ministry of Education Industry University Cooperative Education Project(202102246004,220800006041043,202002142012)the Fundamental Research Funds for the Central Universities(2042023kf1033)。
文摘Recent years have witnessed the ever-increasing performance of Deep Neural Networks(DNNs)in computer vision tasks.However,researchers have identified a potential vulnerability:carefully crafted adversarial examples can easily mislead DNNs into incorrect behavior via the injection of imperceptible modification to the input data.In this survey,we focus on(1)adversarial attack algorithms to generate adversarial examples,(2)adversarial defense techniques to secure DNNs against adversarial examples,and(3)important problems in the realm of adversarial examples beyond attack and defense,including the theoretical explanations,trade-off issues and benign attacks in adversarial examples.Additionally,we draw a brief comparison between recently published surveys on adversarial examples,and identify the future directions for the research of adversarial examples,such as the generalization of methods and the understanding of transferability,that might be solutions to the open problems in this field.
