BACKGROUND Congenital short bowel syndrome(CSBS)is a rare disorder characterized by a congenital shortage in the length of the small intestines,resulting in compromised intestinal functionality,frequently accompanied ...BACKGROUND Congenital short bowel syndrome(CSBS)is a rare disorder characterized by a congenital shortage in the length of the small intestines,resulting in compromised intestinal functionality,frequently accompanied by congenital intestinal malrotation.This study summarizes the experience of enteral and parenteral nutrition(PN)schemes for two cases of CSBS accompanied by intestinal malrotation to provide a reference for this condition.CASE SUMMARY Case 1 underwent surgical intervention 23 days after birth,but experienced postoperative intolerance to oral feeding.Consequently,the patient was transitioned to nasal feeding for 6 months while concurrently receiving round-the-clock PN.Despite ongoing adjustments to the caloric intake of enteral and PN throughout the treatment,cholestatic liver injury persisted.Furthermore,this child developed malnutrition by the age of 1 year.Case 2 received surgical intervention on 2 days after birth,demonstrating favorable tolerance for enteral feeding and intermittent PN.The child exhibited satisfactory growth and development without any associated complications.CONCLUSION CSBS is rarely encountered in clinical practice and is often accompanied by congenital intestinal malrotation.It can be improved with early diagnosis and active surgical intervention.Thus,we recommend early initiation of total PN,which is a highly effective measure in promoting early growth and development.展开更多
As a cutting-edge technology in the field of medical robotics,vascular interventional surgical robots have made remarkable progress in recent years.This paper focuses on the technological innovations of vascular inter...As a cutting-edge technology in the field of medical robotics,vascular interventional surgical robots have made remarkable progress in recent years.This paper focuses on the technological innovations of vascular interventional surgical robots,with particular attention to the system developed by Xu’s team that rapidly secured national patents through China’s Green Innovation Fast-Track.The article elaborates on its key breakthroughs in haptic force feedback,master-slave control accuracy,and multimodal image fusion,and discusses the potential clinical advantages these innovations confer.By benchmarking the system against comparable technologies at home and abroad,the paper forecasts its future applications in healthcare and provides a reference for subsequent R&D and clinical adoption.展开更多
A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis,which can lead to poor quality of sexual life.Here,the association between fo...A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis,which can lead to poor quality of sexual life.Here,the association between foreskin length and sexual dysfunction was evaluated.A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China(Hefei,China).Clinical characteristics,including foreskin length,were collected,and sexual function was assessed by the International Index of Erectile Function-5(IIEF-5)and Premature Ejaculation Diagnostic Tool(PEDT)questionnaires.Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction.Among the 2721 erectile dysfunction(ED)patients and 1064 premature ejaculation(PE)patients,301(11.1%)ED patients and 135(12.7%)PE patients had redundant foreskin,respectively.Men in the PE group were more likely to have redundant foreskin than men in the non-PE group(P=0.004).Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED(adjusted odds ratio[aOR]=1.31,adjusted P=0.04),moderate PE(aOR=1.38,adjusted P=0.02),and probable PE(aOR=1.37,adjusted P=0.03)after adjusting for confounding variables.Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction,especially in PE patients.Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction.展开更多
Prenatal maternal psychological distress,particularly depression,has been increasingly recognized as a factor that influences fetal growth;however,its impact on early childhood development remains less well understood...Prenatal maternal psychological distress,particularly depression,has been increasingly recognized as a factor that influences fetal growth;however,its impact on early childhood development remains less well understood.The present study investigated the association between prenatal depression and children's growth trajectories,as well as the odds of overweight and obesity from 1 to 36 months,while also accounting for maternal anxiety and stress.We analyzed data from 4710 mother-child dyads in the Jiangsu Birth Cohort,assessing maternal psychological distress across trimesters and categorizing participants into groups with mild,moderate,and severe depressive symptomatology.Children's weight-for-length z-scores(WLZ)were used to assess overweight/obesity prevalence,and growth patterns were identified through trajectory models.The results from the generalized estimating equations analysis showed that greater depressive symptomatology during pregnancy was associated with a 28%to 41%increase in the odds of childhood overweight/obesity across all three trimesters,compared with mild depressive symptomatology.We identified five distinct WLZ growth trajectory patterns,and found that mothers with greater depressive symptomatology were 39%–47%more likely to have children who followed a very-high-stable growth trajectory,compared with mothers with mild depressive symptomatology.These findings highlight the significant impact of prenatal depression on adverse growth patterns and childhood overweight/obesity,underscoring the need for early intervention.展开更多
About 25,000 rice T-DNA insertional mutant lines were generated using the vector pCAS04 which has both promoter-trapping and activation-tagging function. Southern blot analysis revealed that about 40% of these mutants...About 25,000 rice T-DNA insertional mutant lines were generated using the vector pCAS04 which has both promoter-trapping and activation-tagging function. Southern blot analysis revealed that about 40% of these mutants were single copy integration and the average T-DNA insertion number was 2.28. By extensive phenotyping in the field, quite a number of agronomically important mutants were obtained. Histochemical GUS assay with 4,310 primary mutants revealed that the GUS-staining frequency was higher than that of the previous reports in various tissues and especially high in flowers. The T-DNA flanking sequences of some mutants were isolated and the T-DNA insertion sites were mapped to the rice genome. The flanking sequence analysis demonstrated the different integration pattern of the right border and left border into rice genome. Compared with Arabidopsis and poplar, it is much varied in the T-DNA border junctions in rice.展开更多
This study aims to compare the prevalence of sexually transmitted infections(STIs)with semen quality in men from couples with primary and secondary infertility.Semen samples were collected from 133 men who requested f...This study aims to compare the prevalence of sexually transmitted infections(STIs)with semen quality in men from couples with primary and secondary infertility.Semen samples were collected from 133 men who requested fertility evaluation.Seminal tract infection with Ureaplasma spp.(UU),Mycoplasma hominis(MH),Mycoplasma genitalium(MG),Chlamydia trachomatis(CT),Neisseria gonorrhoeae(NG),and herpes simplex virus-2(HSV-2)was assessed by PCR-based diagnostic assays.Among all patients,the prevalence of STIs was higher in men from couples with primary infertility than that in men from couples with secondary infertility(39.7%vs 21.7%,P=0.03).The prevalence of UU was 28.8%and 13.3%in men from couples with primary and secondary infertility,respectively.Men from couples with primary infertility were more likely to be positive for UU than men from couples with secondary infertility(P=0.04).Regarding the UU subtype,the prevalence of Ureaplasma urealyticum(Uuu)and Ureaplasma parvum(Uup;including Uup1,Uup3,Uup6,and Uup14)did not differ between the two groups.No associations between the prevalence rates of MH,MG,and CT were found in men from either infertility group.A lower sperm concentration was associated with STI pathogen positivity in men with primary infertility according to the crude model(P=0.04).The crude and adjusted models showed that semen volume(both P=0.03)and semen leukocyte count(both P=0.02)were independently associated with secondary infertility.These findings suggest the importance of classifying the type of infertility during routine diagnosis of seminal tract infections.展开更多
Optoelectronic devices on silicon substrates are essential not only to the optoelectronic integrated circuit but also to low-cost lasers,large-area detectors,and so forth.Although heterogeneous integration of III-V se...Optoelectronic devices on silicon substrates are essential not only to the optoelectronic integrated circuit but also to low-cost lasers,large-area detectors,and so forth.Although heterogeneous integration of III-V semiconductors on Si has been welldeveloped,the thermal dissipation issue and the complicated fabrication process still hinders the development of these devices.The monolithic growth of III-V materials on Si has also been demonstrated by applying complicated buffer layers or interlayers.On the other hand,the growth of lattice-matched B-doped group-III-V materials is an attractive area of research.However,due to the difficulty in growth,the development is still relatively slow.Herein,we present a comprehensive review of the recent achievements in this field.We summarize and discuss the conditions and mechanisms involved in growing B-doped group-III-V materials.The unique surface morphology,crystallinity,and optical properties of the epitaxy correlating with their growth conditions are discussed,along with their respective optoelectronic applications.Finally,we detail the obstacles and challenges to exploit the potential for such practical applications fully.展开更多
Objectives To evaluate the feasibility and safety of a second generation robotic percutaneous coronary intervention(R-PCI)system in China.Background Robotic PCI has been shown to be an effective method for conducting ...Objectives To evaluate the feasibility and safety of a second generation robotic percutaneous coronary intervention(R-PCI)system in China.Background Robotic PCI has been shown to be an effective method for conducting coronary interventions.It has further benefits of more accurate lesion measurement,improved stent deployment,reduced incidence of geographic miss and reduction of operator radiation exposure.Methods This single center evaluation enrolled 10 consecutive patients who had been selected for PCI.Clinical success was defined as residual stenosis<30%and no in-hospital major adverse cardiovascular events.Learning curve effect was assessed by comparing efficiency metrics of early vs.later cases.Results Eleven lesions were treated all successfully without manual interruption or MACE events.Most lesions(63%)were ACC/AHA class B2 and C.Mean procedure time was 57.7±26.4 min,however two procedures were part of live demonstrations.Excluding the two live cases,the mean procedure time was 51.8±23.7 min.Procedural efficiency tended to improve from early cases to later cases based on PCI time(48.3±32.9 vs.25.5±13.0 min,P=0.27),fluoroscopy time(20.3±8.2 vs.12.5±4.6 min,P=0.16),contrast volume(145.0±28.9 vs.102.5±17.1 mL,P=0.05)and Air Kerma dose(1932±978 vs.1007±70 mGy,P=0.31).Conclusions Second generation robotic PCI was safe,effective and there were trends toward improvements in procedural efficiency during this early experience in China.展开更多
BACKGROUND: We aim to investigate effects of metabolic syndrome on onset age and long-termoutcomes in patients with acute coronary syndrome (ACS).METHODS: Patients with ACS (n=6,431) who underwent percutaneous coronar...BACKGROUND: We aim to investigate effects of metabolic syndrome on onset age and long-termoutcomes in patients with acute coronary syndrome (ACS).METHODS: Patients with ACS (n=6,431) who underwent percutaneous coronary interventionfrom January to December 2013 were enrolled. After excluding patients with previous coronary arterydisease, 1,558 patients were diagnosed with early-onset ACS (men aged ≤50 years;women aged≤60 years) and 3,044 patients with late-onset ACS. Baseline characteristics and five-year clinicaloutcomes were measured.RESULTS: Body mass index, triglyceride, low-density lipoprotein cholesterol, and uric acidconcentrations were significantly higher, while the high-density lipoprotein cholesterol (HDL-C)concentration was lower in the early-onset ACS group (P<0.001). Multivariate logistic regression revealedobesity (odds ratio [OR] 1.590, 95% confi dence interval [CI] 1.345–1.881), hypertriglyceridemia (OR 1.403,95% CI 1.185–1.660), and low HDL-C (OR 1.464, 95% CI 1.231–1.742) as independent risk factorsfor early-onset ACS (all P<0.001). The fi ve-year follow-up showed that the incidences of all cause death(1.5% vs. 3.8%, P<0.001), cardiac death (1.1% vs. 2.0%, P=0.023), and recurrent stroke (2.2% vs. 4.2%,P<0.001) were lower, while bleeding events were more frequent in the early-onset ACS group. A subgroupanalysis showed higher incidences of recurrent myocardial infarction (MI) and revascularization in patientswith early-onset ACS and metabolic syndrome.CONCLUSIONS: Obesity, hypertriglyceridemia, and lower HDL-C level are independent riskfactors for early-onset ACS, recurrent MI, and revascularization. The control of metabolic syndromemay reduce the incidence of early-onset ACS and improve the long-term prognosis.展开更多
The anti-sliding stability of a gravity dam along its foundation surface is a key problem in the design of gravity dams.In this study,a sensitivity analysis framework was proposed for investigating the factors affecti...The anti-sliding stability of a gravity dam along its foundation surface is a key problem in the design of gravity dams.In this study,a sensitivity analysis framework was proposed for investigating the factors affecting gravity dam anti-sliding stability along the foundation surface.According to the design specifications,the loads and factors affecting the stability of a gravity dam were comprehensively selected.Afterwards,the sensitivity of the factors was preliminarily analyzed using the Sobol method with Latin hypercube sampling.Then,the results of the sensitivity analysis were verified with those obtained using the Garson method.Finally,the effects of different sampling methods,probability distribution types of factor samples,and ranges of factor values on the analysis results were evaluated.A case study of a typical gravity dam in Yunnan Province of China showed that the dominant factors affecting the gravity dam anti-sliding stability were the anti-shear cohesion,upstream and downstream water levels,anti-shear friction coefficient,uplift pressure reduction coefficient,concrete density,and silt height.Choice of sampling methods showed no significant effect,but the probability distribution type and the range of factor values greatly affected the analysis results.Therefore,these two elements should be sufficiently considered to improve the reliability of the dam anti-sliding stability analysis.展开更多
The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma(OSCC) and adjacent tissues to establish a molecular surgical boundary and provide a cancer progr...The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma(OSCC) and adjacent tissues to establish a molecular surgical boundary and provide a cancer progression model. Biopsy samples from 50 OSCC patients were divided into T(cancer), P1(0–0.5 cm), P2(0.5–1 cm), P3(1–1.5 cm) and P4(1.5–2 cm) groups based on the distances from the visible boundary of the primary focus. Twenty samples of normal mucosa were used as controls. We used immunohistochemical staining and flow cytometry to evaluate p53, p21CIP1/WAF1, e IF4 E and Ki-67 expression and to determine DNA status, respectively. Sub-mucosal invasion was present in the P1 and P2 groups as determined by haematoxylin and eosin staining.Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21CIP1/WAF1 expression displayed an opposite trend. e IF4 E expression decreased from cancerous to normal mucosae. Ki-67 expression, the heteroploidy ratio, S-phase fraction and proliferative index decreased gradually with the distance from the tumour centre. Based on these results, we suggest that the resection boundary in OSCC surgery should be beyond 2 cm from the tumour. Additionally, the adjacent tissues of the primary focus could be used as a model for assessing cancer progression.展开更多
Both boron nitride(BN)and carbon(C)have sp,sp^(2)and sp^(3)hybridization modes,thus resulting in a variety of BN and C polymorphs with similar structures,such as hexagonal BN(hBN)and graphite,cubic BN(cBN)and diamond....Both boron nitride(BN)and carbon(C)have sp,sp^(2)and sp^(3)hybridization modes,thus resulting in a variety of BN and C polymorphs with similar structures,such as hexagonal BN(hBN)and graphite,cubic BN(cBN)and diamond.Here,five types of BN polymorph structures are proposed theoretically,inspired by the graphite-diamond hybrid structures discovered in a recent experiment.These BN polymorphs with graphite-diamond hybrid structures possess excellent mechanical properties with combined high hardness and high ductility,and also exhibit various electronic properties such as semi-conductivity,semi-metallicity,and even one-and two-dimensional conductivity,differing from known insulators hBN and cBN.The simulated diffraction patterns of these BN hybrid structures could account for the unsolved diffraction patterns of intermediate products composed of so-called“compressed hBN”and diamond-like BN,caused by phase transitions in previous experiments.Thus,this work provides a theoretical basis for the presence of these types of hybrid materials during phase transitions between graphite-like and diamond-like BN polymorphs.展开更多
Nonobstructive azoospermia(NOA)is a common cause of infertility and is defined as the complete absence of sperm in ejaculation due to defective spermatogenesis.The aim of this study was to identify the genetic etiolog...Nonobstructive azoospermia(NOA)is a common cause of infertility and is defined as the complete absence of sperm in ejaculation due to defective spermatogenesis.The aim of this study was to identify the genetic etiology of NOA in an infertile male from a Chinese consanguineous family.A homozygous missense variant of the membrane-bound O-acyltransferase domain-containing 1(MBOAT1)gene(c.770C>T,p.Thr257Met)was found by whole-exome sequencing(WES).Bioinformatic analysis also showed that this variant was a pathogenic variant and that the amino acid residue in MBOAT1 was highly conserved in mammals.Quantitative polymerase chain reaction(Q-PCR)analysis showed that the mRNA level of MBOAT1 in the patient was 22.0%lower than that in his father.Furthermore,we screened variants of MBOAT1 in a broader population and found an additional homozygous variant of the MBOAT1 gene in 123 infertile men.Our data identified homozygous variants of the MBOAT1 gene associated with male infertility.This study will provide new insights for researchers to understand the molecular mechanisms of male infertility and will help clinicians make accurate diagnoses.展开更多
A novel amperometric biosensor for the detection of hydrogen peroxide is described. The biosensor was constructed by electrodepositing HRP/PPy membrane on the surface of ferrocenecarboxylic acid mediated sol-gel deriv...A novel amperometric biosensor for the detection of hydrogen peroxide is described. The biosensor was constructed by electrodepositing HRP/PPy membrane on the surface of ferrocenecarboxylic acid mediated sol-gel derived composite carbon electrode. The biosensor gives response to hydrogen peroxide in a few seconds with detection limit of 5×10-7 mol·L-1 (based on signal : noise=3). Linear range is up to 0.2 mmol·L-1.展开更多
BACKGROUND Takotsubo cardiomyopathy(TCM),or stress-induced cardiomyopathy,is associated with adverse prognosis.Limited data suggest that TCM occurring in orthotopic liver transplant(OLT)recipients is associated with e...BACKGROUND Takotsubo cardiomyopathy(TCM),or stress-induced cardiomyopathy,is associated with adverse prognosis.Limited data suggest that TCM occurring in orthotopic liver transplant(OLT)recipients is associated with elevated perioperative risk.AIM To characterize the predictors of TCM in OLT recipients,using a large,multicenter pooled electronic health database.METHODS A multi-institutional database(Explorys Inc,Cleveland,OH,USA),an aggregate of de-identified electronic health record data from 26 United States healthcare systems was surveyed.A cohort of patients with a Systematized Nomenclature of Medicine-Clinical Terms of“liver transplant”between 09/2015 and 09/2020 was identified.Subsequently,individuals who developed a new diagnosis of TCM following OLT were identified.Furthermore,the risk associations with TCM among this patient population were characterized using linear regression.RESULTS Between 09/2015 and 09/2020,of 37718540 patients in the database,38740(0.10%)had a history of OLT(60.6%had an age between 18-65 years,58.1%female).A new diagnosis of TCM was identified in 0.3%of OLT recipients(45.5%had an age between 18-65 years,72.7%female),compared to 0.04%in non-OLT patients[odds ratio(OR):7.98,95%confidence intervals:6.62-9.63,(P<0.0001)].OLT recipients who developed TCM,compared to those who did not,were more likely to be greater than 65 years of age,Caucasian,and female(P<0.05).There was also a significant association with cardiac arrhythmias,especially ventricular arrhythmias(P<0.0001).CONCLUSION TCM was significantly more likely to occur in LT recipients vs non-recipients.Older age,Caucasian ethnicity,female gender,and presence of arrhythmias were significantly associated with TCM in LT recipients.展开更多
Background:Breast cancer is a prevalent malignant tumor affecting females,with treatment options including surgery,radiotherapy,chemotherapy,and endocrine therapy.Methods:This review synthesizes existing literature on...Background:Breast cancer is a prevalent malignant tumor affecting females,with treatment options including surgery,radiotherapy,chemotherapy,and endocrine therapy.Methods:This review synthesizes existing literature on breast cancer stem cells and their applications in breast cancer treatment.PubMed,Web of Science,and other relevant databases were systematically searched using keywords such as“breast cancer stem cells,”“immunotherapy,”“gene therapy,”and“cell therapy.”Studies published in English were included,and their findings were analyzed to provide insights into the characteristics and therapeutic potential of breast cancer stem cells.Results:Breast cancer stem cells exhibit unique properties that contribute to tumor initiation,progression,recurrence,and therapy resistance.Immunotherapy targeting breast cancer stem cells shows promise in overcoming these challenges,but issues such as lack of specificity and drug resistance need to be addressed.Conclusions:Breast cancer stem cells represent promising targets for innovative therapeutic strategies aimed at improving treatment outcomes in breast cancer patients.展开更多
It is well known that coarse-grained super-elastic NiTi shape memory alloys(SMAs)exhibit localized rather than homogeneous martensite transformation(MT),which,however,can be strongly influenced by either internal size...It is well known that coarse-grained super-elastic NiTi shape memory alloys(SMAs)exhibit localized rather than homogeneous martensite transformation(MT),which,however,can be strongly influenced by either internal size(grain size,GS)or the external size(geometric size).The coupled effect of GS and geometric size on the functional properties has not been clearly understood yet.In this work,the super-elasticity,one-way,and stress-assisted two-way shape memory effects of the polycrystalline NiTi SMAs with different aspect ratios(length/width for the gauge section)and different GSs are investigated based on the phase field method.The coupled effect of the aspect ratio and GS on the functional properties is adequately revealed.The simulated results indicate that when the aspect ratio is lower than about 4:1,the stress biaxiality and stress heterogeneity in the gauge section of the sample become more and more obvious with decreasing the aspect ratio,which can significantly influence the microstructure evolution in the process involving external stress.Therefore,the corresponding functional property is strongly dependent on the aspect ratio.With decreasing the GS and the aspect ratio(to be lower than 4:1),both the aspect ratio and GS can affect the MT or martensite reorientation in each grain and the interaction among grains.Thus,due to the strong internal constraint(i.e.,the constraint of grain boundary)and the external constraint(i.e.,the constraint of geometric boundary),the capabilities of the functional properties of NiTi SMAs are gradually weakened and highly dependent on these two factors.展开更多
Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.S...Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.Skeletal muscle,as a major metabolic organ system,undergoes significant remodeling during ALI.However,its specific regulatory contributions remain largely uncharacterized.Methods:Partial(2/3)hepatectomy and acetaminophen were used to induce ALI in male mice.RNA-sequencing(RNA-seq),assay for transposase-accessible chromatin by sequencing(ATAC-seq),chromatin immunoprecipitation,luciferase assay,Western blotting,TUNEL assay,immunohistochemistry,and phase separation assays were performed to reveal the transcriptional axis involved.Serum fibroblast growth factor binding protein 1(FGFBP1)protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.Results:Integrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid(GC)signaling-mediated regulation of fibroblast growth factor 6(FGF6)in skeletal muscle metabolism.Muscle-specific knockdown of GC receptor(GR)exacerbates ALI and suppresses liver regeneration.Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration,with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown.Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling.Moreover,FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation(LLPS)-driven condensate dynamics at the plasma membrane.Circulating FGFBP1 subsequently interacts with hepatic FGF5 through LLPS mechanisms to regulate liver regeneration.Conclusion:Our results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis,providing a potential therapeutic target and treatment strategy for ALI.展开更多
Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
文摘BACKGROUND Congenital short bowel syndrome(CSBS)is a rare disorder characterized by a congenital shortage in the length of the small intestines,resulting in compromised intestinal functionality,frequently accompanied by congenital intestinal malrotation.This study summarizes the experience of enteral and parenteral nutrition(PN)schemes for two cases of CSBS accompanied by intestinal malrotation to provide a reference for this condition.CASE SUMMARY Case 1 underwent surgical intervention 23 days after birth,but experienced postoperative intolerance to oral feeding.Consequently,the patient was transitioned to nasal feeding for 6 months while concurrently receiving round-the-clock PN.Despite ongoing adjustments to the caloric intake of enteral and PN throughout the treatment,cholestatic liver injury persisted.Furthermore,this child developed malnutrition by the age of 1 year.Case 2 received surgical intervention on 2 days after birth,demonstrating favorable tolerance for enteral feeding and intermittent PN.The child exhibited satisfactory growth and development without any associated complications.CONCLUSION CSBS is rarely encountered in clinical practice and is often accompanied by congenital intestinal malrotation.It can be improved with early diagnosis and active surgical intervention.Thus,we recommend early initiation of total PN,which is a highly effective measure in promoting early growth and development.
文摘As a cutting-edge technology in the field of medical robotics,vascular interventional surgical robots have made remarkable progress in recent years.This paper focuses on the technological innovations of vascular interventional surgical robots,with particular attention to the system developed by Xu’s team that rapidly secured national patents through China’s Green Innovation Fast-Track.The article elaborates on its key breakthroughs in haptic force feedback,master-slave control accuracy,and multimodal image fusion,and discusses the potential clinical advantages these innovations confer.By benchmarking the system against comparable technologies at home and abroad,the paper forecasts its future applications in healthcare and provides a reference for subsequent R&D and clinical adoption.
基金supported by the National Natural Science Foundation of China(No.81901543 and No.81971333)the Key Research and Development Project of Anhui Province(2022e07020014)the Joint Fund for Medical Artificial Intelligence(MAI2022Q010).
文摘A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis,which can lead to poor quality of sexual life.Here,the association between foreskin length and sexual dysfunction was evaluated.A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China(Hefei,China).Clinical characteristics,including foreskin length,were collected,and sexual function was assessed by the International Index of Erectile Function-5(IIEF-5)and Premature Ejaculation Diagnostic Tool(PEDT)questionnaires.Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction.Among the 2721 erectile dysfunction(ED)patients and 1064 premature ejaculation(PE)patients,301(11.1%)ED patients and 135(12.7%)PE patients had redundant foreskin,respectively.Men in the PE group were more likely to have redundant foreskin than men in the non-PE group(P=0.004).Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED(adjusted odds ratio[aOR]=1.31,adjusted P=0.04),moderate PE(aOR=1.38,adjusted P=0.02),and probable PE(aOR=1.37,adjusted P=0.03)after adjusting for confounding variables.Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction,especially in PE patients.Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction.
基金supported by the National Natural Science Foundation of China(Grant No.82373581 to Yuan Lin).
文摘Prenatal maternal psychological distress,particularly depression,has been increasingly recognized as a factor that influences fetal growth;however,its impact on early childhood development remains less well understood.The present study investigated the association between prenatal depression and children's growth trajectories,as well as the odds of overweight and obesity from 1 to 36 months,while also accounting for maternal anxiety and stress.We analyzed data from 4710 mother-child dyads in the Jiangsu Birth Cohort,assessing maternal psychological distress across trimesters and categorizing participants into groups with mild,moderate,and severe depressive symptomatology.Children's weight-for-length z-scores(WLZ)were used to assess overweight/obesity prevalence,and growth patterns were identified through trajectory models.The results from the generalized estimating equations analysis showed that greater depressive symptomatology during pregnancy was associated with a 28%to 41%increase in the odds of childhood overweight/obesity across all three trimesters,compared with mild depressive symptomatology.We identified five distinct WLZ growth trajectory patterns,and found that mothers with greater depressive symptomatology were 39%–47%more likely to have children who followed a very-high-stable growth trajectory,compared with mothers with mild depressive symptomatology.These findings highlight the significant impact of prenatal depression on adverse growth patterns and childhood overweight/obesity,underscoring the need for early intervention.
基金supported by the National High Technology Research and Development Program of China (No.2002AAZ2001)the National Natural Sciences Foundation of China (No.30270758 and 30621001)
文摘About 25,000 rice T-DNA insertional mutant lines were generated using the vector pCAS04 which has both promoter-trapping and activation-tagging function. Southern blot analysis revealed that about 40% of these mutants were single copy integration and the average T-DNA insertion number was 2.28. By extensive phenotyping in the field, quite a number of agronomically important mutants were obtained. Histochemical GUS assay with 4,310 primary mutants revealed that the GUS-staining frequency was higher than that of the previous reports in various tissues and especially high in flowers. The T-DNA flanking sequences of some mutants were isolated and the T-DNA insertion sites were mapped to the rice genome. The flanking sequence analysis demonstrated the different integration pattern of the right border and left border into rice genome. Compared with Arabidopsis and poplar, it is much varied in the T-DNA border junctions in rice.
基金supported by the National Key Research and Development Project(2019YFA0802600)the National Natural Science Foundation of China(No.81901543,81901545,81971333,82001495,32002354)+2 种基金the Fundamental Research Funds for the Central Universities(WK9110000063)the State Key Laboratory of Reproductive Medicine(SKLRM-K201904)the Natural Science Foundation of Anhui Provincial of China(1908085QH315).
文摘This study aims to compare the prevalence of sexually transmitted infections(STIs)with semen quality in men from couples with primary and secondary infertility.Semen samples were collected from 133 men who requested fertility evaluation.Seminal tract infection with Ureaplasma spp.(UU),Mycoplasma hominis(MH),Mycoplasma genitalium(MG),Chlamydia trachomatis(CT),Neisseria gonorrhoeae(NG),and herpes simplex virus-2(HSV-2)was assessed by PCR-based diagnostic assays.Among all patients,the prevalence of STIs was higher in men from couples with primary infertility than that in men from couples with secondary infertility(39.7%vs 21.7%,P=0.03).The prevalence of UU was 28.8%and 13.3%in men from couples with primary and secondary infertility,respectively.Men from couples with primary infertility were more likely to be positive for UU than men from couples with secondary infertility(P=0.04).Regarding the UU subtype,the prevalence of Ureaplasma urealyticum(Uuu)and Ureaplasma parvum(Uup;including Uup1,Uup3,Uup6,and Uup14)did not differ between the two groups.No associations between the prevalence rates of MH,MG,and CT were found in men from either infertility group.A lower sperm concentration was associated with STI pathogen positivity in men with primary infertility according to the crude model(P=0.04).The crude and adjusted models showed that semen volume(both P=0.03)and semen leukocyte count(both P=0.02)were independently associated with secondary infertility.These findings suggest the importance of classifying the type of infertility during routine diagnosis of seminal tract infections.
文摘Optoelectronic devices on silicon substrates are essential not only to the optoelectronic integrated circuit but also to low-cost lasers,large-area detectors,and so forth.Although heterogeneous integration of III-V semiconductors on Si has been welldeveloped,the thermal dissipation issue and the complicated fabrication process still hinders the development of these devices.The monolithic growth of III-V materials on Si has also been demonstrated by applying complicated buffer layers or interlayers.On the other hand,the growth of lattice-matched B-doped group-III-V materials is an attractive area of research.However,due to the difficulty in growth,the development is still relatively slow.Herein,we present a comprehensive review of the recent achievements in this field.We summarize and discuss the conditions and mechanisms involved in growing B-doped group-III-V materials.The unique surface morphology,crystallinity,and optical properties of the epitaxy correlating with their growth conditions are discussed,along with their respective optoelectronic applications.Finally,we detail the obstacles and challenges to exploit the potential for such practical applications fully.
文摘Objectives To evaluate the feasibility and safety of a second generation robotic percutaneous coronary intervention(R-PCI)system in China.Background Robotic PCI has been shown to be an effective method for conducting coronary interventions.It has further benefits of more accurate lesion measurement,improved stent deployment,reduced incidence of geographic miss and reduction of operator radiation exposure.Methods This single center evaluation enrolled 10 consecutive patients who had been selected for PCI.Clinical success was defined as residual stenosis<30%and no in-hospital major adverse cardiovascular events.Learning curve effect was assessed by comparing efficiency metrics of early vs.later cases.Results Eleven lesions were treated all successfully without manual interruption or MACE events.Most lesions(63%)were ACC/AHA class B2 and C.Mean procedure time was 57.7±26.4 min,however two procedures were part of live demonstrations.Excluding the two live cases,the mean procedure time was 51.8±23.7 min.Procedural efficiency tended to improve from early cases to later cases based on PCI time(48.3±32.9 vs.25.5±13.0 min,P=0.27),fluoroscopy time(20.3±8.2 vs.12.5±4.6 min,P=0.16),contrast volume(145.0±28.9 vs.102.5±17.1 mL,P=0.05)and Air Kerma dose(1932±978 vs.1007±70 mGy,P=0.31).Conclusions Second generation robotic PCI was safe,effective and there were trends toward improvements in procedural efficiency during this early experience in China.
基金supported by the National Key Researchand Development Program of China (2016YFC130130 [Subtopic:2016YFC1301301]).
文摘BACKGROUND: We aim to investigate effects of metabolic syndrome on onset age and long-termoutcomes in patients with acute coronary syndrome (ACS).METHODS: Patients with ACS (n=6,431) who underwent percutaneous coronary interventionfrom January to December 2013 were enrolled. After excluding patients with previous coronary arterydisease, 1,558 patients were diagnosed with early-onset ACS (men aged ≤50 years;women aged≤60 years) and 3,044 patients with late-onset ACS. Baseline characteristics and five-year clinicaloutcomes were measured.RESULTS: Body mass index, triglyceride, low-density lipoprotein cholesterol, and uric acidconcentrations were significantly higher, while the high-density lipoprotein cholesterol (HDL-C)concentration was lower in the early-onset ACS group (P<0.001). Multivariate logistic regression revealedobesity (odds ratio [OR] 1.590, 95% confi dence interval [CI] 1.345–1.881), hypertriglyceridemia (OR 1.403,95% CI 1.185–1.660), and low HDL-C (OR 1.464, 95% CI 1.231–1.742) as independent risk factorsfor early-onset ACS (all P<0.001). The fi ve-year follow-up showed that the incidences of all cause death(1.5% vs. 3.8%, P<0.001), cardiac death (1.1% vs. 2.0%, P=0.023), and recurrent stroke (2.2% vs. 4.2%,P<0.001) were lower, while bleeding events were more frequent in the early-onset ACS group. A subgroupanalysis showed higher incidences of recurrent myocardial infarction (MI) and revascularization in patientswith early-onset ACS and metabolic syndrome.CONCLUSIONS: Obesity, hypertriglyceridemia, and lower HDL-C level are independent riskfactors for early-onset ACS, recurrent MI, and revascularization. The control of metabolic syndromemay reduce the incidence of early-onset ACS and improve the long-term prognosis.
基金supported by the National Natural Science Foundation of China(Grant No.52079120).
文摘The anti-sliding stability of a gravity dam along its foundation surface is a key problem in the design of gravity dams.In this study,a sensitivity analysis framework was proposed for investigating the factors affecting gravity dam anti-sliding stability along the foundation surface.According to the design specifications,the loads and factors affecting the stability of a gravity dam were comprehensively selected.Afterwards,the sensitivity of the factors was preliminarily analyzed using the Sobol method with Latin hypercube sampling.Then,the results of the sensitivity analysis were verified with those obtained using the Garson method.Finally,the effects of different sampling methods,probability distribution types of factor samples,and ranges of factor values on the analysis results were evaluated.A case study of a typical gravity dam in Yunnan Province of China showed that the dominant factors affecting the gravity dam anti-sliding stability were the anti-shear cohesion,upstream and downstream water levels,anti-shear friction coefficient,uplift pressure reduction coefficient,concrete density,and silt height.Choice of sampling methods showed no significant effect,but the probability distribution type and the range of factor values greatly affected the analysis results.Therefore,these two elements should be sufficiently considered to improve the reliability of the dam anti-sliding stability analysis.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81001209 and 81172578)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 81321002)
文摘The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma(OSCC) and adjacent tissues to establish a molecular surgical boundary and provide a cancer progression model. Biopsy samples from 50 OSCC patients were divided into T(cancer), P1(0–0.5 cm), P2(0.5–1 cm), P3(1–1.5 cm) and P4(1.5–2 cm) groups based on the distances from the visible boundary of the primary focus. Twenty samples of normal mucosa were used as controls. We used immunohistochemical staining and flow cytometry to evaluate p53, p21CIP1/WAF1, e IF4 E and Ki-67 expression and to determine DNA status, respectively. Sub-mucosal invasion was present in the P1 and P2 groups as determined by haematoxylin and eosin staining.Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21CIP1/WAF1 expression displayed an opposite trend. e IF4 E expression decreased from cancerous to normal mucosae. Ki-67 expression, the heteroploidy ratio, S-phase fraction and proliferative index decreased gradually with the distance from the tumour centre. Based on these results, we suggest that the resection boundary in OSCC surgery should be beyond 2 cm from the tumour. Additionally, the adjacent tissues of the primary focus could be used as a model for assessing cancer progression.
基金supported by the National Natural Science Foundation of China(Grant Nos.52090020,91963203,U20A20238,51772260,52073245,and 51722209)the National Key R&D Program of China(Grant Nos.2018YFA0703400 and 2018YFA0305900)+1 种基金the Natural Science Foundation for Distinguished Young Scholars of Hebei Province of China(Grant No.E2018203349)the Talent Research Project in Hebei Province(Grant No.2020HBQZYC003)。
文摘Both boron nitride(BN)and carbon(C)have sp,sp^(2)and sp^(3)hybridization modes,thus resulting in a variety of BN and C polymorphs with similar structures,such as hexagonal BN(hBN)and graphite,cubic BN(cBN)and diamond.Here,five types of BN polymorph structures are proposed theoretically,inspired by the graphite-diamond hybrid structures discovered in a recent experiment.These BN polymorphs with graphite-diamond hybrid structures possess excellent mechanical properties with combined high hardness and high ductility,and also exhibit various electronic properties such as semi-conductivity,semi-metallicity,and even one-and two-dimensional conductivity,differing from known insulators hBN and cBN.The simulated diffraction patterns of these BN hybrid structures could account for the unsolved diffraction patterns of intermediate products composed of so-called“compressed hBN”and diamond-like BN,caused by phase transitions in previous experiments.Thus,this work provides a theoretical basis for the presence of these types of hybrid materials during phase transitions between graphite-like and diamond-like BN polymorphs.
基金This research was supported by the National Key Research and Development Project(2019YFA0802600)the National Natural Science Foundation of China(81971333).
文摘Nonobstructive azoospermia(NOA)is a common cause of infertility and is defined as the complete absence of sperm in ejaculation due to defective spermatogenesis.The aim of this study was to identify the genetic etiology of NOA in an infertile male from a Chinese consanguineous family.A homozygous missense variant of the membrane-bound O-acyltransferase domain-containing 1(MBOAT1)gene(c.770C>T,p.Thr257Met)was found by whole-exome sequencing(WES).Bioinformatic analysis also showed that this variant was a pathogenic variant and that the amino acid residue in MBOAT1 was highly conserved in mammals.Quantitative polymerase chain reaction(Q-PCR)analysis showed that the mRNA level of MBOAT1 in the patient was 22.0%lower than that in his father.Furthermore,we screened variants of MBOAT1 in a broader population and found an additional homozygous variant of the MBOAT1 gene in 123 infertile men.Our data identified homozygous variants of the MBOAT1 gene associated with male infertility.This study will provide new insights for researchers to understand the molecular mechanisms of male infertility and will help clinicians make accurate diagnoses.
文摘A novel amperometric biosensor for the detection of hydrogen peroxide is described. The biosensor was constructed by electrodepositing HRP/PPy membrane on the surface of ferrocenecarboxylic acid mediated sol-gel derived composite carbon electrode. The biosensor gives response to hydrogen peroxide in a few seconds with detection limit of 5×10-7 mol·L-1 (based on signal : noise=3). Linear range is up to 0.2 mmol·L-1.
文摘BACKGROUND Takotsubo cardiomyopathy(TCM),or stress-induced cardiomyopathy,is associated with adverse prognosis.Limited data suggest that TCM occurring in orthotopic liver transplant(OLT)recipients is associated with elevated perioperative risk.AIM To characterize the predictors of TCM in OLT recipients,using a large,multicenter pooled electronic health database.METHODS A multi-institutional database(Explorys Inc,Cleveland,OH,USA),an aggregate of de-identified electronic health record data from 26 United States healthcare systems was surveyed.A cohort of patients with a Systematized Nomenclature of Medicine-Clinical Terms of“liver transplant”between 09/2015 and 09/2020 was identified.Subsequently,individuals who developed a new diagnosis of TCM following OLT were identified.Furthermore,the risk associations with TCM among this patient population were characterized using linear regression.RESULTS Between 09/2015 and 09/2020,of 37718540 patients in the database,38740(0.10%)had a history of OLT(60.6%had an age between 18-65 years,58.1%female).A new diagnosis of TCM was identified in 0.3%of OLT recipients(45.5%had an age between 18-65 years,72.7%female),compared to 0.04%in non-OLT patients[odds ratio(OR):7.98,95%confidence intervals:6.62-9.63,(P<0.0001)].OLT recipients who developed TCM,compared to those who did not,were more likely to be greater than 65 years of age,Caucasian,and female(P<0.05).There was also a significant association with cardiac arrhythmias,especially ventricular arrhythmias(P<0.0001).CONCLUSION TCM was significantly more likely to occur in LT recipients vs non-recipients.Older age,Caucasian ethnicity,female gender,and presence of arrhythmias were significantly associated with TCM in LT recipients.
基金supported by Jiangsu Province“333”Project(BRA2020380).
文摘Background:Breast cancer is a prevalent malignant tumor affecting females,with treatment options including surgery,radiotherapy,chemotherapy,and endocrine therapy.Methods:This review synthesizes existing literature on breast cancer stem cells and their applications in breast cancer treatment.PubMed,Web of Science,and other relevant databases were systematically searched using keywords such as“breast cancer stem cells,”“immunotherapy,”“gene therapy,”and“cell therapy.”Studies published in English were included,and their findings were analyzed to provide insights into the characteristics and therapeutic potential of breast cancer stem cells.Results:Breast cancer stem cells exhibit unique properties that contribute to tumor initiation,progression,recurrence,and therapy resistance.Immunotherapy targeting breast cancer stem cells shows promise in overcoming these challenges,but issues such as lack of specificity and drug resistance need to be addressed.Conclusions:Breast cancer stem cells represent promising targets for innovative therapeutic strategies aimed at improving treatment outcomes in breast cancer patients.
基金supported by the National Natural Science Foundation of China (Grant Nos.12202294 and 12022208)the Project funded by China Postdoctoral Science Foundation (Grant No.2022M712243)the Fundamental Research Funds for the Central Universities (Grant No.2023SCU12098).
文摘It is well known that coarse-grained super-elastic NiTi shape memory alloys(SMAs)exhibit localized rather than homogeneous martensite transformation(MT),which,however,can be strongly influenced by either internal size(grain size,GS)or the external size(geometric size).The coupled effect of GS and geometric size on the functional properties has not been clearly understood yet.In this work,the super-elasticity,one-way,and stress-assisted two-way shape memory effects of the polycrystalline NiTi SMAs with different aspect ratios(length/width for the gauge section)and different GSs are investigated based on the phase field method.The coupled effect of the aspect ratio and GS on the functional properties is adequately revealed.The simulated results indicate that when the aspect ratio is lower than about 4:1,the stress biaxiality and stress heterogeneity in the gauge section of the sample become more and more obvious with decreasing the aspect ratio,which can significantly influence the microstructure evolution in the process involving external stress.Therefore,the corresponding functional property is strongly dependent on the aspect ratio.With decreasing the GS and the aspect ratio(to be lower than 4:1),both the aspect ratio and GS can affect the MT or martensite reorientation in each grain and the interaction among grains.Thus,due to the strong internal constraint(i.e.,the constraint of grain boundary)and the external constraint(i.e.,the constraint of geometric boundary),the capabilities of the functional properties of NiTi SMAs are gradually weakened and highly dependent on these two factors.
基金supported by the NSFC Distinguished Young Scholars Fund(82325010)the National Natural Science Foundation of China(82370874)+4 种基金the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212700)the Major Natural Science Project of the Scientific Research and Innovation Plan of Shanghai Municipal Commission of Education(2023ZKZD17)the Shanghai Research Center for Endocrine and Metabolic Diseases(2022ZZ01002)the Shanghai Key Discipline of Public Health Grants Award(GWVI-11.1-20)the Basic Scientific Research Project(General Cultivation Program)of Shanghai Sixth People’s Hospital(ynms202203).
文摘Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.Skeletal muscle,as a major metabolic organ system,undergoes significant remodeling during ALI.However,its specific regulatory contributions remain largely uncharacterized.Methods:Partial(2/3)hepatectomy and acetaminophen were used to induce ALI in male mice.RNA-sequencing(RNA-seq),assay for transposase-accessible chromatin by sequencing(ATAC-seq),chromatin immunoprecipitation,luciferase assay,Western blotting,TUNEL assay,immunohistochemistry,and phase separation assays were performed to reveal the transcriptional axis involved.Serum fibroblast growth factor binding protein 1(FGFBP1)protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.Results:Integrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid(GC)signaling-mediated regulation of fibroblast growth factor 6(FGF6)in skeletal muscle metabolism.Muscle-specific knockdown of GC receptor(GR)exacerbates ALI and suppresses liver regeneration.Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration,with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown.Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling.Moreover,FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation(LLPS)-driven condensate dynamics at the plasma membrane.Circulating FGFBP1 subsequently interacts with hepatic FGF5 through LLPS mechanisms to regulate liver regeneration.Conclusion:Our results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis,providing a potential therapeutic target and treatment strategy for ALI.
基金supported by the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.