Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successfulanterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel...Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successfulanterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. En-hancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return topre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B)healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis,stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-Bhealing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulateT-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities inthe near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular andmolecular levels, describe studies in animal models, and provide a future direction for research.展开更多
BACKGROUND Anterior cruciate ligament reconstruction(ACLR)is the dominant clinical modality for the treatment of anterior cruciate ligament injuries.The success of ACLR is largely dependent on tendon-bone healing,and ...BACKGROUND Anterior cruciate ligament reconstruction(ACLR)is the dominant clinical modality for the treatment of anterior cruciate ligament injuries.The success of ACLR is largely dependent on tendon-bone healing,and stem cell biotherapies are often used to facilitate this process.Histone lactylation modifications are involved in the regulation of various diseases.Lactate dehydrogenase A(LDHA)has been shown to play an important role in exosomes.AIM To explore the regulation of tendon-bone healing after ACLR by LDHA in exosomes derived from bone marrow mesenchymal stem cells(BMSC-Exos).METHODS BMSC-Exos and LDHA were characterized and analyzed by transmission electron microscopy,qNano,immunofluorescence and western blotting assay.The corresponding low expression cell lines were obtained using RNA interference transfection;LDHA expression in rat bone tissues after ACLR was analyzed by western blotting.The volume of newborn bone tissues was monitored by micro-computed tomography imaging.Tendon and fibrocartilage regeneration were further analyzed and calculated by histological analysis,including hematoxylin and eosin and Safranin O-Fast green staining,respectively;LDHA levels of chondrocyte stem cells(CSPCs)after co-incubation with BMSC-Exos were analyzed by western blotting.Extracellularly secreted lactic acid content was determined by lactate assay kit.Cell viability was assessed by cell counting kit 8 assay,and the proliferation and differentiation ability of cells was further examined by the expression of collagen II,SOX9 and aggrecan.Histone H3K18 lactylation modification was analyzed by western blotting.H3K18 La binding on bone morphogenetic protein 7(BMP7)promoter was analyzed by chromatin immunoprecipitation-quantitative polymerase chain reaction;BMP7 promoter activity was analyzed by dual luciferase reporter gene;BMP7 protein expression was analyzed using quantitative polymerase chain reaction and western blotting.Then,the proliferation of CSPCs promoted by BMSC-Exos LDHA was analyzed by protein expression levels of LDHA,BMP7,collagen II,SOX9,aggrecan,extracellular lactate content,and cell counting kit 8 assay.RESULTS The spherical nanosized BMSC-Exos could be uptaken by CSPCs.LDHA was highly expressed in BMSC-Exos,which could infiltrate into the bone tissue of ACLR rats and promoted the generation of new bone tissue,as well as significantly increased the regeneration of tendon and fibrocartilage.Co-incubation of CSPCs with high-expressing LDHA BMSC-Exos increased the secretion of lactate content from CSPCs,cell viability,and the expression of markers related to cell proliferation and differentiation,including collagen II,SOX9,and aggrecan;LDHA in BMSC-Exos upregulated BMP7 through histone H3K18 lactate modification;high LDHA expression reversed the knockdown of BMP7,further increasing the proliferation and differentiation of CSPCs,thereby inducing cartilage formation.CONCLUSION LDHA in BMSC-Exos promotes BMP7 expression via H3K18 lactylation modification,which further promotes tendon-bone healing after ACLR.展开更多
Tendon-bone healing remains a significant clinical challenge due to the high risk of re-rupture following injury.While mesenchymal stem cells(MSCs)show great potential in enhancing tendon-bone healing,their clinical a...Tendon-bone healing remains a significant clinical challenge due to the high risk of re-rupture following injury.While mesenchymal stem cells(MSCs)show great potential in enhancing tendon-bone healing,their clinical application is limited by issues such as low delivery efficiency,restricted differentiation potential,and potential immunogenicity.Recently,various strategies combining MSCs with other approaches,such as preconditioning,biomaterial integration,gene modification,and exosome application,have been developed,resulting in improved therapeutic outcomes.This review explored the current methods used to optimize MSC therapy for tendon-bone healing,examining the advantages,disadvantages,and underlying mechanisms of each approach,providing a foundation for future research and clinical applications.展开更多
Neuromorphic circuits based on superconducting tunnel junctions have attracted much attention due to their highspeed computing capabilities and low energy consumption.Josephson junction circuits can effectively mimic ...Neuromorphic circuits based on superconducting tunnel junctions have attracted much attention due to their highspeed computing capabilities and low energy consumption.Josephson junction circuits can effectively mimic biological neural dynamics.Leveraging these advantages,we construct a Josephson junction neuron-like model with a phasedependent dissipative current,referred to as a memristive current.The proposed memristive Josephson junction model exhibits complex dynamical behaviors.Furthermore,considering the effect of a fast-modulated synapse,we explore synchronization phenomena in coupled networks under varying coupling conductances and excitatory/inhibitory interactions.Finally,we extend the neuromorphic Josephson junction model—exhibiting complex dynamics—to the field of image encryption.These results not only enrich the understanding of the dynamical characteristics of memristive Josephson junctions but also provide a theoretical basis and technical support for the development of new neural networks and their applications in information security technology.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary sa...Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary salt intake,and diets deficient in vegetables and fruits.Due to the often subtle and nonspecific early symptoms,coupled with the lack of routine screening programs,a significant proportion of GC cases are diagnosed at advanced stages.The etiology of GC is multifactorial,and diagnosis is confirmed histologically through endoscopic biopsy,followed by staging via computed tomography,positron emission tomography,staging laparoscopy,and endoscopic ultrasound.Treatment strategies typically involve a multidisciplinary approach including chemotherapy,surgical resection,radiotherapy,and emerging immunotherapeutic options.Despite advances in diagnostic and therapeutic modalities,the prognosis of advanced GC remains poor,with high rates of recurrence and metastasis.In recent years,increasing attention has been given to the role of tight junction(TJ)proteins in the pathogenesis and progression of GC.TJ proteins,critical components of epithelial barrier function,have been implicated in various stages of gastric carcinogenesis,from intestinal metaplasia to invasion and metastasis.Infection and inflammation,particularly due to Helicobacter pylori,disrupt TJ integrity,compromising the gastric mucosal barrier and facilitating neoplastic transformation.This review synthesizes current evidence from PubMed,EMBASE,Google Scholar,ScienceDirect,SpringerLink,and other reputable databases to provide a comprehensive overview of the involvement of TJ proteins in GC.By elucidating the molecular interplay between TJ dysregulation and gastric tumorigenesis,this work aims to highlight the potential of TJ proteins as novel diagnostic biomarkers and therapeutic targets in GC management.展开更多
Control over charge transport in molecular–scale devices requires a deep understanding of how minute structural changes influence electronic properties.Here,we demonstrate dual transport regimes in tunnel junctions o...Control over charge transport in molecular–scale devices requires a deep understanding of how minute structural changes influence electronic properties.Here,we demonstrate dual transport regimes in tunnel junctions of n-alk-1-yne(CnA)molecules with gold electrodes driven by conformational bifurcation—the emergence of two nearly isoenergetic(planar and skewed)molecular conformers(dihedral anglesα=180°andα≈65°at the alkyne terminus in the gas phase).Although the energy differences are small,these subtle conformational differences manifest as distinct transport behaviors,uncovered through unsupervised machine learning,which identified two junction groups:“short”and“long”chains,with distinct attenuation factors(β_(short)≈1.0 vs.β_(long)≈0.74)and contact conductances(G_(c,short)≈200μS vs.G_(c,long)≈8μS).This dramatic impact of the dihedral angle exceeds the impact of the inter-ring twist angle in biphenyl-based junctions and rivals changes induced by switching from gold to platinum electrodes or from monothiol to dithiol anchors in oligoacene and oligophenylene junctions.X-ray photoelectron spectroscopy(XPS)confirmed this bifurcation,linking the“short”and“long”groups to planar and skewed conformers,with dihedrals remarkably agreeing with the gas-phase values.This work establishes conformational bifurcation as a promising route for designing programmable nanotransport properties through anchor-group control.展开更多
Photocatalysis uses solar energy to convert nitrogen and water directly into ammonia,helping reduce dependence on fossil fuels and offering a way to integrate the nitrogen cycle into a clean energy network.Ohmic junct...Photocatalysis uses solar energy to convert nitrogen and water directly into ammonia,helping reduce dependence on fossil fuels and offering a way to integrate the nitrogen cycle into a clean energy network.Ohmic junctions between metals and semiconductors have demonstrated significant advantages in enhancing stability and reducing carrier recombination,but their application in photocatalytic nitrogen fixation is limited due to the difficulty of work function matching and the complexity of fabrication processes.In this study,density functional theory(DFT) calculations were used to confirm the work function matching between Bi and Bi_(2)Ti_(2)O_(7)(BTO),ensuring the formation of an Ohmic junction.A Bi-Bi_(2)Ti_(2)O_(7)(B-BTO) composite was successfully synthesized via a one-step hydrothermal method,using bismuth nitrate and titanium sulfate as precursors.Compared to pure BTO,the B-BTO heterojunction,driven by dual electron injection from both metal Bi and BTO,significantly increased the ammonia synthesis rate to 686.95 μmol g^(-1)h^(-1),making it the most active nitrogen fixation material among similar pyrochlorebased catalysts to date.The differential charge density calculations,photocurrent(i-t) measurements,and photoluminescence(PL) tests further validate the role of Ohmic contacts in enhancing charge transfer and prolonging carrier lifetimes.This research provides valuable insight into the application of Ohmic junctions in photocatalytic nitrogen fixation and contributes to advancements in this field.展开更多
AIM To quantitatively assess rotatory and anterior-posterior instability in vivo after anterior cruciate ligament(ACL) reconstruction using bone-patellar tendon-bone(BTB) autografts, and to clarify the influence of tu...AIM To quantitatively assess rotatory and anterior-posterior instability in vivo after anterior cruciate ligament(ACL) reconstruction using bone-patellar tendon-bone(BTB) autografts, and to clarify the influence of tunnel positions on the knee stability.METHODS Single-bundle ACL reconstruction with BTB autograft was performed on 50 patients with a mean age of 28 years using the trans-tibial(TT)(n = 20) and trans-portal(TP)(n = 30) techniques. Femoral and tibial tunnel positions were identified from the high-resolution 3 D-CT bone models two weeks after surgery. Anterolateral rotatory translation was examined using a Slocum anterolateral rotatory instability test in open magnetic resonance imaging(MRI) 1.0-1.5 years after surgery, by measuring anterior tibial translation at the medial and lateral compartments on its sagittal images. Anterior-posterior stability was evaluated with a Kneelax3 arthrometer.RESULTS A total of 40 patients(80%) were finally followed up. Femoral tunnel positions were shallower(P < 0.01) and higher(P < 0.001), and tibial tunnel positions were more posterior(P < 0.05) in the TT group compared with the TP group. Anterolateral rotatory translations in reconstructed knees were significantly correlated with the shallow femoral tunnel positions(R = 0.42, P < 0.01), and the rotatory translations were greater in the TT group(3.2 ± 1.6 mm) than in the TP group(2.0 ± 1.8 mm)(P < 0.05). Side-to-side differences of Kneelax3 arthrometer were 1.5 ± 1.3 mm in the TT, and 1.7 ± 1.6 mm in the TP group(N.S.). Lysholm scores, KOOS subscales and reinjury rate showed no difference between the two groups.CONCLUSION Anterolateral rotatory instability significantly correlated shallow femoral tunnel positions after ACL reconstruction using BTB autografts. Clinical outcomes, rotatory and anterior-posterior stability were overall satisfactory in both techniques, but the TT technique located femoral tunnels in shallower and higher positions, and tibial tunnels in more posterior positions than the TP technique, thus increased the anterolateral rotation. Anatomic ACL reconstruction with BTB autografts may restore knee function and stability.展开更多
The presence of excessive reactive oxygen species(ROS)after injuries to the enthesis could lead to cellular oxidative damage,high inflammatory response,chronic inflammation,and limited fibrochondral inductivity,making...The presence of excessive reactive oxygen species(ROS)after injuries to the enthesis could lead to cellular oxidative damage,high inflammatory response,chronic inflammation,and limited fibrochondral inductivity,making tissue repair and functional recovery difficult.Here,a multifunctional silk fibroin nanofiber modified with polydopamine and kartogenin was designed and fabricated to not only effectively reduce inflammation by scavenging ROS in the early stage of the enthesis healing but also enhance fibrocartilage formation with fibrochondrogenic induction in the later stages.The in vitro results confirmed the antioxidant capability and the fibrochondral inductivity of the functionalized nanofibers.In vivo studies showed that the multifunctional nanofiber can significantly improve the integration of tendon-bone and accelerate the regeneration of interface tissue,resulting in an excellent biomechanical property.Thus,the incorporation of antioxidant and bio-active molecules into extracellular matrix-like biomaterials in interface tissue engineering provides an integrative approach that facilitates damaged tissue regeneration and functional recovery,thereby improving the clinical outcome of the engineered tissue.展开更多
Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and ...Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren’s syndrome(SS).Employing a multifaceted approach involving patient biopsies,non-obese diabetic(NOD)mice as a SS model,salivary gland acinar cell-specific tricellulin conditional knockout(TricCKO)mice,and IFN-γ-stimulated salivary gland epithelial cells,we investigated the role of tricellulin in SS-related hyposalivation.Our data revealed diminished levels of tricellulin in salivary glands of SS patients.Similarly,NOD mice displayed a reduction in tricellulin expression from the onset of the disease,concomitant with hyposecretion and an increase in salivary albumin content.Consistent with these findings,TricCKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals.Mechanistically,the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin.Treatment with AT1001,a TJ sealer,ameliorated epithelial barrier dysfunction,restored tricellulin expression,and consequently alleviated hyposalivation in NOD mice.Importantly,treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage.Collectively,we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS.Our findings highlight tricellulin as a potential therapeutic target for hyposecretion,particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.展开更多
Multiferroic tunnel junctions(MFTJs),which combine tunneling magnetoresistance(TMR)and electroresistance(TER)efects,have emerged as key candidates for data storage.Two-dimensional van der Waals(vdW)MFTJs,in particular...Multiferroic tunnel junctions(MFTJs),which combine tunneling magnetoresistance(TMR)and electroresistance(TER)efects,have emerged as key candidates for data storage.Two-dimensional van der Waals(vdW)MFTJs,in particular,are promising spintronic devices for the post-Moore era.However,these vdW MFTJs are typically based on multiferroics composed of ferromagnetic and ferroelectric materials or multilayer magnetic materials with sliding ferroelectricity,which increases device fabrication complexity.In this work,we design a vdW MFTJ using bilayer MoPtGe_(2)S_(6),a material with homologous multiferroicity in each monolayer,combined with symmetric PtTe_(2)electrodes.Using frst-principles calculations based on density functional theory and nonequilibrium Green's functions,we theoretically explore the spin-polarized electronic transport properties of this MFTJ.By controlling the ferroelectric and ferromagnetic polarization directions of bilayer MoPtGe_(2)S_(6),the MFTJ can exhibit six distinct non-volatile resistance states,with maximum TMR(137%)and TER(1943%)ratios.Under biaxial strain,TMR and TER can increase to 265%and 4210%,respectively.The TER ratio also increases to 2186%under a 0.1 V bias voltage.Remarkably,the MFTJ exhibits a pronounced spin-fltering and a signifcant negative diferential resistance efect.These fndings not only highlight the potential of monolayer multiferroic MoPtGe_(2)S_(6)for MFTJs but also ofer valuable theoretical insights for future experimental investigations.展开更多
BACKGROUND The spectrum of gastric submucosal tumors(SMTs)in the upper gastrointestinal system ranges from non-neoplastic to malignant lesions,with gastrointestinal stromal tumors exhibiting inherent malignant potenti...BACKGROUND The spectrum of gastric submucosal tumors(SMTs)in the upper gastrointestinal system ranges from non-neoplastic to malignant lesions,with gastrointestinal stromal tumors exhibiting inherent malignant potential.However,the diagnosis of SMTs remains challenging,and treatment methods,especially for tumors located at the cardia or esophagogastric junction(EGJ),are not well established.Minimally invasive techniques-such as endoscopic submucosal dissection(ESD),submucosal tunneling endoscopic resection(STER),and laparoscopic wedge resection(LWR)-have been developed for these lesions.However,comparative data on their feasibility,safety,and clinical outcomes in these locations remain limited.AIM To compare ESD,STER,and LWR for SMTs at the EGJ or cardia,focusing on procedural feasibility.METHODS This single-center retrospective study included patients with SMTs less than 45 mm from the muscularis propria,growing intraluminally at the EGJ or cardia,and treated with ESD,STER,or LWR between July 2014 and September 2022.The primary outcome was relapse-free survival during follow-up.RESULTS The median age(interquartile range)was 53.0(40.0-57.5),43.0(39.0-57.0),and 56.0(43.0-64.0)years for ESD,STER,and LWR,respectively.The median follow-up time(interquartile range)was 60.0(26.5-66.5),24.0(13.0-38.0),and 35.0(21.0-60.0)months.LWR had the largest tumors(30.0 mm)and the highest rate of high-risk gastrointestinal stromal tumors(68.0%,P<0.001).Tumor recurrence occurred in one LWR patient(4.0%,P=0.600).En bloc and macroscopic resection rates were 100%(P=1.000),but microscopic resection rates differed(P=0.021).Significant minor complications occurred in 5 patients(10.0%),all grade IIIa.Tumor location(cardia/fundus,P=0.006)and prolonged procedure time(P<0.001)were significantly associated with complications.CONCLUSION ESD,STER,and LWR are effective for SMTs at the EGJ and cardia,with minor complications associated with tumor location and procedure time,and comparable recurrence rates.展开更多
Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the an...Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the antitumor activity of CD8+T cells.Our study investigates the role of JAML+CD8+T cells in HCC.Methods:We utilized time-of-flight mass cytometry and an orthotopic mouse model of HCC to examine histone modifications in tumor-infiltrating immune cells undergoing immunotherapy.Flow cytometry was used to assess CD4+T cells differentiation and JAML expression in CD8+T cells infiltrating HCC.Correlation analysis revealed a strong positive correlation between lactate dehydrogenase A+(LDHA+)CD4+T cells and JAML+CD8+T cells.Subsequently,we evaluated the therapeutic effects of an agonistic anti-JAML antibody,both alone and combined with immunotherapy.Finally,RNA sequencing was conducted to identify potential regulatory mechanisms.Results:Immunotherapy significantly increased the percentage of CD8+T cells infiltrating HCC and induced histone modifications,such as H3K18 lactylation(H3K18la)in CD4+T cells.Flow cytometry analysis revealed that lactate promotes the differentiation of CD4+T cells into Th1 cells.LDHA,an enzyme that converts pyruvate to lactate,plays a key role in this process.Correlation analysis revealed a strong positive relationship between LDHA+CD4+T cells and JAML+CD8+T cells in patients who responded to immunotherapy.Moreover,high JAML expression in CD8+T cells was associated with a more favorable prognosis.In vivo experiments demonstrated that agonistic anti-JAML antibody therapy reduced tumor volume and significantly prolonged the survival of tumor-bearing mice,independent of the effects of anti-programmed cell death protein ligand-1 antibody(αPD-L1)-mediated immunotherapy.Pathway enrichment analysis further revealed that JAML enhances CTL responses through the oxidative phosphorylation pathway.Conclusions:Activation of JAML enhances CTL responses in HCC treatment,independent ofαPD-L1-mediated immunotherapy,providing a promising strategy for advanced HCC.展开更多
Methane(CH4),the predominant component of natural gas and shale gas,is regarded as a promising carbon feedstock for chemical synthesis[1].However,considering the extreme stability of CH4 molecules,it's quite chall...Methane(CH4),the predominant component of natural gas and shale gas,is regarded as a promising carbon feedstock for chemical synthesis[1].However,considering the extreme stability of CH4 molecules,it's quite challenging in simultaneously achieving high activity and selectivity for target products under mild conditions,especially when synthesizing high-value C2t chemicals such as ethanol[2].The conversion of methane to ethanol by photocatalysis is promising for achieving transformation under ambient temperature and pressure conditions.Currently,the apparent quantum efficiency(AQE)of solar-driven methane-to-ethanol conversion is generally below 0.5%[3,4].Furthermore,the stability of photocatalysts remains inadequate,offering substantial potential for further improvement.展开更多
This study examines the influence of magnetic field and temperature on the transient voltage of a polycrystalline silicon radial junction solar cell in a dynamic regime under multispectral illumination. Radial junctio...This study examines the influence of magnetic field and temperature on the transient voltage of a polycrystalline silicon radial junction solar cell in a dynamic regime under multispectral illumination. Radial junction solar cells represent a major advancement in photovoltaic technologies, as they optimize light absorption and charge collection efficiency. The focus is on the impact of the magnetic field and temperature on the decay of transient voltage, which provides crucial information on recombination processes and the lifetime of minority carriers. The results reveal that the magnetic field tends to increase the transient voltage by directly affecting the transient electron density. Indeed, for B > 7 × 10−5 T, the magnetic field prolongs the relaxation time by increasing the transient voltage amplitude. Additionally, rising temperatures accelerate (ranging from 290 K to 450 K) recombination processes, thereby reducing the transient voltage, although this effect is moderated by the presence of a magnetic field. The study highlights the complex interaction between magnetic field and temperature, with significant impacts on the transient behaviour.展开更多
Aim:The aim of this study was to investigate the factors affecting treatment success in children that got either pyeloplasty or J stent placement in ureteropelvic junction obstruction(UPJO).Patients and Methods:The st...Aim:The aim of this study was to investigate the factors affecting treatment success in children that got either pyeloplasty or J stent placement in ureteropelvic junction obstruction(UPJO).Patients and Methods:The study comprised 126 patients who either J stent placement or pyeloplasty performed by the same physician for UPJO from 2012 to 2022.The criteria for surgical intervention adhered to the European Association of Urology(EAU)recommendations.Symptomatic patients with verified obstruction,with a split renal function(SRF)over 40%,low-grade hydronephrosis(Society of Fetal Urology grade 2),and an obstructive segment measuring less than 1 cm,had Double-J stent placement.Furthermore,in infants exhibiting poor health or development retardation,a J stent was inserted as a temporary measure to alleviate obstruction and maintain renal function,notwithstanding the recommendation for pyeloplasty.Results:The treatment success rate was 43.9%in the J stent group and 88.4%in the pyeloplasty group,with a statistically significant difference(p<0.001).The kind of procedure(pyeloplasty vs.stent)was the sole independent prognostic factor predicting treatment success(HR:4.77,p<0.001)in the multiple logistic regression analysis.No statistically significant change was observed in preoperative and postoperative SRF(48%vs.48.5%,p=0.923)among patients with stent failure,confirming a transient preservation of functional advantage.Conclusion:The placement of a stent may have restricted success rates in specific patients with UPJO.Preserving renal function may be advantageous until definitive surgery,particularly in cases where there are hazards associated with anesthesia and invasive procedures.展开更多
In the rapidly evolving field of modern technology,near-infrared(NIR)photodetectors are extremely crucial for efficient and reliable optical communications.The graphene/GaAs Schottky junction photodetector leverages g...In the rapidly evolving field of modern technology,near-infrared(NIR)photodetectors are extremely crucial for efficient and reliable optical communications.The graphene/GaAs Schottky junction photodetector leverages graphene’s exceptional carrier mobility and broadband absorption,coupled with GaAs’s strong absorption in the NIR spectrum,to achieve high responsivity and rapid response times.Here,we present a NIR photodetector employing a graphene/GaAs Schottky junction tailored for communication wavelengths.We fabricated high-performance graphene/GaAs Schottky junction devices with interdigitated electrodes of varying finger widths,systematically investigating their impact on device performance.The experimental results demonstrate that incorporating interdigitated electrodes significantly enhances the collection efficiency of photogenerated carriers in graphene/GaAs photodetectors.When illuminated by 808 nm NIR light at an intensity of 7.23 mW/cm^(2),the device achieves an impressive switch ratio of 10^(7),along with a high responsivity of 40.1 mA/W and a remarkable detectivity of 2.89×10^(13)Jones.Additionally,the device is characterized by rapid response times,with rise and fall times of 18.5 and 17.5μs,respectively,at a 3 dB bandwidth.These findings underscore the significant potential of high-performance graphene/GaAs photodetectors for applications in NIR optoelectronic systems.展开更多
BACKGROUND Congenital junctional ectopic tachycardia(CJET)is a rare but life-threatening arrhythmia in neonates and infants,often refractory to conventional antiar-rhythmic therapy.Ivabradine,a selective inhibitor of ...BACKGROUND Congenital junctional ectopic tachycardia(CJET)is a rare but life-threatening arrhythmia in neonates and infants,often refractory to conventional antiar-rhythmic therapy.Ivabradine,a selective inhibitor of hyperpolarization-activated cyclic nucleotide-gated channels,has emerged as a promising drug for CJET management.AIM To evaluate the efficacy and safety of ivabradine in the management of CJET.Specifically,this study aims to analyze the dosing strategies,treatment outcomes,and the role of ivabradine as monotherapy or adjunct therapy in patients who have previously received other antiarrhythmic medications.Additionally,this review seeks to assess the impact of ivabradine on heart rate(HR)control,rhythm conversion,and its overall safety profile to provide evidence-based insights into its clinical use for CJET management.METHODS This systematic review aims to evaluate the outcomes of ivabradine,either as monotherapy or as an adjunctive therapy,in the treatment of CJET.A compre-hensive literature search was conducted across multiple electronic databases to identify relevant studies investigating the use of ivabradine in CJET.Stringent inclusion and exclusion criteria were applied to ensure the inclusion of high-quality,peer-reviewed studies.Data extraction and quality assessment were performed independently by two reviewers.RESULTS Ten studies,comprising 6 case reports,3 case series,and 1 cohort study,met the inclusion criteria.Ivabradine doses ranged from 0.025 to 0.28 mg/kg/dose,administered either as monotherapy or in combination with various antiar-rhythmic medications.Overall,ivabradine demonstrated promising results in achieving HR control,conversion to sinus rhythm,or stabilization of junctional rhythm.No significant adverse effects related to ivabradine were reported.CONCLUSION The available evidence suggests that ivabradine may be an effective adjunctive therapy or,in some cases,a potential monotherapy for the management of CJET,particularly in cases refractory to traditional antiarrhythmic medications.However,the current evidence is limited by the small sample sizes and retrospective nature of the included studies.Well-designed prospective studies with larger cohorts and longer follow-up periods are warranted to further elucidate the role of ivabradine in CJET management.展开更多
Zinc oxide(ZnO),as a broadband gap semiconductor material,exhibits unique physical and chemical properties that make it highly suitable for optoelectronics,piezoelectric devices,and gas-sensitive sensors,showing signi...Zinc oxide(ZnO),as a broadband gap semiconductor material,exhibits unique physical and chemical properties that make it highly suitable for optoelectronics,piezoelectric devices,and gas-sensitive sensors,showing significant potential for various applications.This paper focuses on the regulation and application of ZnO-based p-n junctions and piezoelectric devices.It discusses in detail the preparation of ZnO materials,the construction of p-n junctions,the optimization of piezoelectric device performance,and its application in various fields.By employing different preparation methods and strategies,high-quality ZnO thin films can be grown,and effective control of p-type conductivity achieved.This study provides both a theoretical foundation and technical support for controlling the performance of ZnO-based piezoelectric devices,as well as paving new pathways for the broader application of ZnO materials.展开更多
基金Project (No. 81171687/H0604) supported by the National Natural Science Foundation of China
文摘Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successfulanterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. En-hancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return topre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B)healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis,stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-Bhealing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulateT-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities inthe near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular andmolecular levels, describe studies in animal models, and provide a future direction for research.
文摘BACKGROUND Anterior cruciate ligament reconstruction(ACLR)is the dominant clinical modality for the treatment of anterior cruciate ligament injuries.The success of ACLR is largely dependent on tendon-bone healing,and stem cell biotherapies are often used to facilitate this process.Histone lactylation modifications are involved in the regulation of various diseases.Lactate dehydrogenase A(LDHA)has been shown to play an important role in exosomes.AIM To explore the regulation of tendon-bone healing after ACLR by LDHA in exosomes derived from bone marrow mesenchymal stem cells(BMSC-Exos).METHODS BMSC-Exos and LDHA were characterized and analyzed by transmission electron microscopy,qNano,immunofluorescence and western blotting assay.The corresponding low expression cell lines were obtained using RNA interference transfection;LDHA expression in rat bone tissues after ACLR was analyzed by western blotting.The volume of newborn bone tissues was monitored by micro-computed tomography imaging.Tendon and fibrocartilage regeneration were further analyzed and calculated by histological analysis,including hematoxylin and eosin and Safranin O-Fast green staining,respectively;LDHA levels of chondrocyte stem cells(CSPCs)after co-incubation with BMSC-Exos were analyzed by western blotting.Extracellularly secreted lactic acid content was determined by lactate assay kit.Cell viability was assessed by cell counting kit 8 assay,and the proliferation and differentiation ability of cells was further examined by the expression of collagen II,SOX9 and aggrecan.Histone H3K18 lactylation modification was analyzed by western blotting.H3K18 La binding on bone morphogenetic protein 7(BMP7)promoter was analyzed by chromatin immunoprecipitation-quantitative polymerase chain reaction;BMP7 promoter activity was analyzed by dual luciferase reporter gene;BMP7 protein expression was analyzed using quantitative polymerase chain reaction and western blotting.Then,the proliferation of CSPCs promoted by BMSC-Exos LDHA was analyzed by protein expression levels of LDHA,BMP7,collagen II,SOX9,aggrecan,extracellular lactate content,and cell counting kit 8 assay.RESULTS The spherical nanosized BMSC-Exos could be uptaken by CSPCs.LDHA was highly expressed in BMSC-Exos,which could infiltrate into the bone tissue of ACLR rats and promoted the generation of new bone tissue,as well as significantly increased the regeneration of tendon and fibrocartilage.Co-incubation of CSPCs with high-expressing LDHA BMSC-Exos increased the secretion of lactate content from CSPCs,cell viability,and the expression of markers related to cell proliferation and differentiation,including collagen II,SOX9,and aggrecan;LDHA in BMSC-Exos upregulated BMP7 through histone H3K18 lactate modification;high LDHA expression reversed the knockdown of BMP7,further increasing the proliferation and differentiation of CSPCs,thereby inducing cartilage formation.CONCLUSION LDHA in BMSC-Exos promotes BMP7 expression via H3K18 lactylation modification,which further promotes tendon-bone healing after ACLR.
基金Jinhua Public Welfare Technology Application Research Project,No.2025-4-229Zhejiang Province Medical and Health Science and Technology Plan,No.2022KY1343.
文摘Tendon-bone healing remains a significant clinical challenge due to the high risk of re-rupture following injury.While mesenchymal stem cells(MSCs)show great potential in enhancing tendon-bone healing,their clinical application is limited by issues such as low delivery efficiency,restricted differentiation potential,and potential immunogenicity.Recently,various strategies combining MSCs with other approaches,such as preconditioning,biomaterial integration,gene modification,and exosome application,have been developed,resulting in improved therapeutic outcomes.This review explored the current methods used to optimize MSC therapy for tendon-bone healing,examining the advantages,disadvantages,and underlying mechanisms of each approach,providing a foundation for future research and clinical applications.
基金supported by the National Natural Science Foundation of China(Grant No.12302070)the Natural Science Foundation of Ningxia(Grant No.2024AAC05002)+1 种基金the Youth Science and Technology Talent Cultivation Project of Ningxiathe Ningxia Science and Technology Leading Talent Training Program(Grant No.2022GKLRLX04)。
文摘Neuromorphic circuits based on superconducting tunnel junctions have attracted much attention due to their highspeed computing capabilities and low energy consumption.Josephson junction circuits can effectively mimic biological neural dynamics.Leveraging these advantages,we construct a Josephson junction neuron-like model with a phasedependent dissipative current,referred to as a memristive current.The proposed memristive Josephson junction model exhibits complex dynamical behaviors.Furthermore,considering the effect of a fast-modulated synapse,we explore synchronization phenomena in coupled networks under varying coupling conductances and excitatory/inhibitory interactions.Finally,we extend the neuromorphic Josephson junction model—exhibiting complex dynamics—to the field of image encryption.These results not only enrich the understanding of the dynamical characteristics of memristive Josephson junctions but also provide a theoretical basis and technical support for the development of new neural networks and their applications in information security technology.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
文摘Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary salt intake,and diets deficient in vegetables and fruits.Due to the often subtle and nonspecific early symptoms,coupled with the lack of routine screening programs,a significant proportion of GC cases are diagnosed at advanced stages.The etiology of GC is multifactorial,and diagnosis is confirmed histologically through endoscopic biopsy,followed by staging via computed tomography,positron emission tomography,staging laparoscopy,and endoscopic ultrasound.Treatment strategies typically involve a multidisciplinary approach including chemotherapy,surgical resection,radiotherapy,and emerging immunotherapeutic options.Despite advances in diagnostic and therapeutic modalities,the prognosis of advanced GC remains poor,with high rates of recurrence and metastasis.In recent years,increasing attention has been given to the role of tight junction(TJ)proteins in the pathogenesis and progression of GC.TJ proteins,critical components of epithelial barrier function,have been implicated in various stages of gastric carcinogenesis,from intestinal metaplasia to invasion and metastasis.Infection and inflammation,particularly due to Helicobacter pylori,disrupt TJ integrity,compromising the gastric mucosal barrier and facilitating neoplastic transformation.This review synthesizes current evidence from PubMed,EMBASE,Google Scholar,ScienceDirect,SpringerLink,and other reputable databases to provide a comprehensive overview of the involvement of TJ proteins in GC.By elucidating the molecular interplay between TJ dysregulation and gastric tumorigenesis,this work aims to highlight the potential of TJ proteins as novel diagnostic biomarkers and therapeutic targets in GC management.
基金financial support from the National Key R&D Program of China(2023YFA1407100)the National Natural Science Foundation of China(22373026)+1 种基金Guangdong Science and Technology Department(2021B0301030005,STKJ2023072,GDZX2304005,GDZX2504001,and 2021QN02X538)Ioan Bâldea gratefully acknowledges computational support by the state of Baden-Württemberg through bwHPC and the German Research Foundation through Grant Nos.INST 40/575-1,35/1597-1,and 35/1134-1(JUSTUS 2,bwUniCluster 2/3,and bwForCluster/MLS&WISO/HELIX 2).
文摘Control over charge transport in molecular–scale devices requires a deep understanding of how minute structural changes influence electronic properties.Here,we demonstrate dual transport regimes in tunnel junctions of n-alk-1-yne(CnA)molecules with gold electrodes driven by conformational bifurcation—the emergence of two nearly isoenergetic(planar and skewed)molecular conformers(dihedral anglesα=180°andα≈65°at the alkyne terminus in the gas phase).Although the energy differences are small,these subtle conformational differences manifest as distinct transport behaviors,uncovered through unsupervised machine learning,which identified two junction groups:“short”and“long”chains,with distinct attenuation factors(β_(short)≈1.0 vs.β_(long)≈0.74)and contact conductances(G_(c,short)≈200μS vs.G_(c,long)≈8μS).This dramatic impact of the dihedral angle exceeds the impact of the inter-ring twist angle in biphenyl-based junctions and rivals changes induced by switching from gold to platinum electrodes or from monothiol to dithiol anchors in oligoacene and oligophenylene junctions.X-ray photoelectron spectroscopy(XPS)confirmed this bifurcation,linking the“short”and“long”groups to planar and skewed conformers,with dihedrals remarkably agreeing with the gas-phase values.This work establishes conformational bifurcation as a promising route for designing programmable nanotransport properties through anchor-group control.
基金supported by the Natural Science Foundation of China (NSFC,No.52372212)。
文摘Photocatalysis uses solar energy to convert nitrogen and water directly into ammonia,helping reduce dependence on fossil fuels and offering a way to integrate the nitrogen cycle into a clean energy network.Ohmic junctions between metals and semiconductors have demonstrated significant advantages in enhancing stability and reducing carrier recombination,but their application in photocatalytic nitrogen fixation is limited due to the difficulty of work function matching and the complexity of fabrication processes.In this study,density functional theory(DFT) calculations were used to confirm the work function matching between Bi and Bi_(2)Ti_(2)O_(7)(BTO),ensuring the formation of an Ohmic junction.A Bi-Bi_(2)Ti_(2)O_(7)(B-BTO) composite was successfully synthesized via a one-step hydrothermal method,using bismuth nitrate and titanium sulfate as precursors.Compared to pure BTO,the B-BTO heterojunction,driven by dual electron injection from both metal Bi and BTO,significantly increased the ammonia synthesis rate to 686.95 μmol g^(-1)h^(-1),making it the most active nitrogen fixation material among similar pyrochlorebased catalysts to date.The differential charge density calculations,photocurrent(i-t) measurements,and photoluminescence(PL) tests further validate the role of Ohmic contacts in enhancing charge transfer and prolonging carrier lifetimes.This research provides valuable insight into the application of Ohmic junctions in photocatalytic nitrogen fixation and contributes to advancements in this field.
基金Supported by JSPS Fellowships for Research Abroad,No.H27-787International Research Fund for Subsidy of Kyushu University School of Medicine Alumni
文摘AIM To quantitatively assess rotatory and anterior-posterior instability in vivo after anterior cruciate ligament(ACL) reconstruction using bone-patellar tendon-bone(BTB) autografts, and to clarify the influence of tunnel positions on the knee stability.METHODS Single-bundle ACL reconstruction with BTB autograft was performed on 50 patients with a mean age of 28 years using the trans-tibial(TT)(n = 20) and trans-portal(TP)(n = 30) techniques. Femoral and tibial tunnel positions were identified from the high-resolution 3 D-CT bone models two weeks after surgery. Anterolateral rotatory translation was examined using a Slocum anterolateral rotatory instability test in open magnetic resonance imaging(MRI) 1.0-1.5 years after surgery, by measuring anterior tibial translation at the medial and lateral compartments on its sagittal images. Anterior-posterior stability was evaluated with a Kneelax3 arthrometer.RESULTS A total of 40 patients(80%) were finally followed up. Femoral tunnel positions were shallower(P < 0.01) and higher(P < 0.001), and tibial tunnel positions were more posterior(P < 0.05) in the TT group compared with the TP group. Anterolateral rotatory translations in reconstructed knees were significantly correlated with the shallow femoral tunnel positions(R = 0.42, P < 0.01), and the rotatory translations were greater in the TT group(3.2 ± 1.6 mm) than in the TP group(2.0 ± 1.8 mm)(P < 0.05). Side-to-side differences of Kneelax3 arthrometer were 1.5 ± 1.3 mm in the TT, and 1.7 ± 1.6 mm in the TP group(N.S.). Lysholm scores, KOOS subscales and reinjury rate showed no difference between the two groups.CONCLUSION Anterolateral rotatory instability significantly correlated shallow femoral tunnel positions after ACL reconstruction using BTB autografts. Clinical outcomes, rotatory and anterior-posterior stability were overall satisfactory in both techniques, but the TT technique located femoral tunnels in shallower and higher positions, and tibial tunnels in more posterior positions than the TP technique, thus increased the anterolateral rotation. Anatomic ACL reconstruction with BTB autografts may restore knee function and stability.
基金supported financially by the National Natural Science Foundation of China[No.11532004,11832008]Innovation and Attracting Talents Program for College and University(“111”Project)[No.B06023]。
文摘The presence of excessive reactive oxygen species(ROS)after injuries to the enthesis could lead to cellular oxidative damage,high inflammatory response,chronic inflammation,and limited fibrochondral inductivity,making tissue repair and functional recovery difficult.Here,a multifunctional silk fibroin nanofiber modified with polydopamine and kartogenin was designed and fabricated to not only effectively reduce inflammation by scavenging ROS in the early stage of the enthesis healing but also enhance fibrocartilage formation with fibrochondrogenic induction in the later stages.The in vitro results confirmed the antioxidant capability and the fibrochondral inductivity of the functionalized nanofibers.In vivo studies showed that the multifunctional nanofiber can significantly improve the integration of tendon-bone and accelerate the regeneration of interface tissue,resulting in an excellent biomechanical property.Thus,the incorporation of antioxidant and bio-active molecules into extracellular matrix-like biomaterials in interface tissue engineering provides an integrative approach that facilitates damaged tissue regeneration and functional recovery,thereby improving the clinical outcome of the engineered tissue.
基金supported by the National Natural Science Foundation of China(grants 31972908,81991500,81991502,and 32030010)Beijing Natural Science Foundation(grant 7202082).
文摘Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren’s syndrome(SS).Employing a multifaceted approach involving patient biopsies,non-obese diabetic(NOD)mice as a SS model,salivary gland acinar cell-specific tricellulin conditional knockout(TricCKO)mice,and IFN-γ-stimulated salivary gland epithelial cells,we investigated the role of tricellulin in SS-related hyposalivation.Our data revealed diminished levels of tricellulin in salivary glands of SS patients.Similarly,NOD mice displayed a reduction in tricellulin expression from the onset of the disease,concomitant with hyposecretion and an increase in salivary albumin content.Consistent with these findings,TricCKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals.Mechanistically,the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin.Treatment with AT1001,a TJ sealer,ameliorated epithelial barrier dysfunction,restored tricellulin expression,and consequently alleviated hyposalivation in NOD mice.Importantly,treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage.Collectively,we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS.Our findings highlight tricellulin as a potential therapeutic target for hyposecretion,particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
基金supported by the National Key R&D Program of China(Grant No.2022YFB3505301)the National Key R&D Program of Shanxi Province(Grant No.202302050201014)+1 种基金the National Natural Science Foundation of China(Grant No.12304148)the Natural Science Basic Research Program of Shanxi Province(Grant No.202203021222219)。
文摘Multiferroic tunnel junctions(MFTJs),which combine tunneling magnetoresistance(TMR)and electroresistance(TER)efects,have emerged as key candidates for data storage.Two-dimensional van der Waals(vdW)MFTJs,in particular,are promising spintronic devices for the post-Moore era.However,these vdW MFTJs are typically based on multiferroics composed of ferromagnetic and ferroelectric materials or multilayer magnetic materials with sliding ferroelectricity,which increases device fabrication complexity.In this work,we design a vdW MFTJ using bilayer MoPtGe_(2)S_(6),a material with homologous multiferroicity in each monolayer,combined with symmetric PtTe_(2)electrodes.Using frst-principles calculations based on density functional theory and nonequilibrium Green's functions,we theoretically explore the spin-polarized electronic transport properties of this MFTJ.By controlling the ferroelectric and ferromagnetic polarization directions of bilayer MoPtGe_(2)S_(6),the MFTJ can exhibit six distinct non-volatile resistance states,with maximum TMR(137%)and TER(1943%)ratios.Under biaxial strain,TMR and TER can increase to 265%and 4210%,respectively.The TER ratio also increases to 2186%under a 0.1 V bias voltage.Remarkably,the MFTJ exhibits a pronounced spin-fltering and a signifcant negative diferential resistance efect.These fndings not only highlight the potential of monolayer multiferroic MoPtGe_(2)S_(6)for MFTJs but also ofer valuable theoretical insights for future experimental investigations.
文摘BACKGROUND The spectrum of gastric submucosal tumors(SMTs)in the upper gastrointestinal system ranges from non-neoplastic to malignant lesions,with gastrointestinal stromal tumors exhibiting inherent malignant potential.However,the diagnosis of SMTs remains challenging,and treatment methods,especially for tumors located at the cardia or esophagogastric junction(EGJ),are not well established.Minimally invasive techniques-such as endoscopic submucosal dissection(ESD),submucosal tunneling endoscopic resection(STER),and laparoscopic wedge resection(LWR)-have been developed for these lesions.However,comparative data on their feasibility,safety,and clinical outcomes in these locations remain limited.AIM To compare ESD,STER,and LWR for SMTs at the EGJ or cardia,focusing on procedural feasibility.METHODS This single-center retrospective study included patients with SMTs less than 45 mm from the muscularis propria,growing intraluminally at the EGJ or cardia,and treated with ESD,STER,or LWR between July 2014 and September 2022.The primary outcome was relapse-free survival during follow-up.RESULTS The median age(interquartile range)was 53.0(40.0-57.5),43.0(39.0-57.0),and 56.0(43.0-64.0)years for ESD,STER,and LWR,respectively.The median follow-up time(interquartile range)was 60.0(26.5-66.5),24.0(13.0-38.0),and 35.0(21.0-60.0)months.LWR had the largest tumors(30.0 mm)and the highest rate of high-risk gastrointestinal stromal tumors(68.0%,P<0.001).Tumor recurrence occurred in one LWR patient(4.0%,P=0.600).En bloc and macroscopic resection rates were 100%(P=1.000),but microscopic resection rates differed(P=0.021).Significant minor complications occurred in 5 patients(10.0%),all grade IIIa.Tumor location(cardia/fundus,P=0.006)and prolonged procedure time(P<0.001)were significantly associated with complications.CONCLUSION ESD,STER,and LWR are effective for SMTs at the EGJ and cardia,with minor complications associated with tumor location and procedure time,and comparable recurrence rates.
基金funded by the Major Research Plan of the National Natural Science Foundation of China(No.92159202)the National Key Research and Development Program of China(No.2021YFA1100500)+1 种基金the Leading Innovation Team Project of Hangzhou Medical College(No.CXLJ202401)the Key Research and Development Plan of Zhejiang Provincial Department of Science and Technology(No.2024C03051)。
文摘Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the antitumor activity of CD8+T cells.Our study investigates the role of JAML+CD8+T cells in HCC.Methods:We utilized time-of-flight mass cytometry and an orthotopic mouse model of HCC to examine histone modifications in tumor-infiltrating immune cells undergoing immunotherapy.Flow cytometry was used to assess CD4+T cells differentiation and JAML expression in CD8+T cells infiltrating HCC.Correlation analysis revealed a strong positive correlation between lactate dehydrogenase A+(LDHA+)CD4+T cells and JAML+CD8+T cells.Subsequently,we evaluated the therapeutic effects of an agonistic anti-JAML antibody,both alone and combined with immunotherapy.Finally,RNA sequencing was conducted to identify potential regulatory mechanisms.Results:Immunotherapy significantly increased the percentage of CD8+T cells infiltrating HCC and induced histone modifications,such as H3K18 lactylation(H3K18la)in CD4+T cells.Flow cytometry analysis revealed that lactate promotes the differentiation of CD4+T cells into Th1 cells.LDHA,an enzyme that converts pyruvate to lactate,plays a key role in this process.Correlation analysis revealed a strong positive relationship between LDHA+CD4+T cells and JAML+CD8+T cells in patients who responded to immunotherapy.Moreover,high JAML expression in CD8+T cells was associated with a more favorable prognosis.In vivo experiments demonstrated that agonistic anti-JAML antibody therapy reduced tumor volume and significantly prolonged the survival of tumor-bearing mice,independent of the effects of anti-programmed cell death protein ligand-1 antibody(αPD-L1)-mediated immunotherapy.Pathway enrichment analysis further revealed that JAML enhances CTL responses through the oxidative phosphorylation pathway.Conclusions:Activation of JAML enhances CTL responses in HCC treatment,independent ofαPD-L1-mediated immunotherapy,providing a promising strategy for advanced HCC.
基金the support from the National Natural Science Foundation of China(52202306)Program from Guangdong Introducing Innovative and Entrepreneurial Teams(2019ZT08L101 and RCTDPT-2020-001)+1 种基金Shenzhen Key Laboratory of Eco-materials and Renewable Energy(ZDSYS20200922160400001)the Provincial Talent Plan of Guangdong(2023TB0012).
文摘Methane(CH4),the predominant component of natural gas and shale gas,is regarded as a promising carbon feedstock for chemical synthesis[1].However,considering the extreme stability of CH4 molecules,it's quite challenging in simultaneously achieving high activity and selectivity for target products under mild conditions,especially when synthesizing high-value C2t chemicals such as ethanol[2].The conversion of methane to ethanol by photocatalysis is promising for achieving transformation under ambient temperature and pressure conditions.Currently,the apparent quantum efficiency(AQE)of solar-driven methane-to-ethanol conversion is generally below 0.5%[3,4].Furthermore,the stability of photocatalysts remains inadequate,offering substantial potential for further improvement.
文摘This study examines the influence of magnetic field and temperature on the transient voltage of a polycrystalline silicon radial junction solar cell in a dynamic regime under multispectral illumination. Radial junction solar cells represent a major advancement in photovoltaic technologies, as they optimize light absorption and charge collection efficiency. The focus is on the impact of the magnetic field and temperature on the decay of transient voltage, which provides crucial information on recombination processes and the lifetime of minority carriers. The results reveal that the magnetic field tends to increase the transient voltage by directly affecting the transient electron density. Indeed, for B > 7 × 10−5 T, the magnetic field prolongs the relaxation time by increasing the transient voltage amplitude. Additionally, rising temperatures accelerate (ranging from 290 K to 450 K) recombination processes, thereby reducing the transient voltage, although this effect is moderated by the presence of a magnetic field. The study highlights the complex interaction between magnetic field and temperature, with significant impacts on the transient behaviour.
文摘Aim:The aim of this study was to investigate the factors affecting treatment success in children that got either pyeloplasty or J stent placement in ureteropelvic junction obstruction(UPJO).Patients and Methods:The study comprised 126 patients who either J stent placement or pyeloplasty performed by the same physician for UPJO from 2012 to 2022.The criteria for surgical intervention adhered to the European Association of Urology(EAU)recommendations.Symptomatic patients with verified obstruction,with a split renal function(SRF)over 40%,low-grade hydronephrosis(Society of Fetal Urology grade 2),and an obstructive segment measuring less than 1 cm,had Double-J stent placement.Furthermore,in infants exhibiting poor health or development retardation,a J stent was inserted as a temporary measure to alleviate obstruction and maintain renal function,notwithstanding the recommendation for pyeloplasty.Results:The treatment success rate was 43.9%in the J stent group and 88.4%in the pyeloplasty group,with a statistically significant difference(p<0.001).The kind of procedure(pyeloplasty vs.stent)was the sole independent prognostic factor predicting treatment success(HR:4.77,p<0.001)in the multiple logistic regression analysis.No statistically significant change was observed in preoperative and postoperative SRF(48%vs.48.5%,p=0.923)among patients with stent failure,confirming a transient preservation of functional advantage.Conclusion:The placement of a stent may have restricted success rates in specific patients with UPJO.Preserving renal function may be advantageous until definitive surgery,particularly in cases where there are hazards associated with anesthesia and invasive procedures.
基金supported by the National Natural Science Foundation of China(62375279)Suzhou Industrial Science and Technology Program(SYG202340,SJC2023004)Distinguished Young Scholar Fund of Natural Science Foundation of Jiangsu Province(BK20240125).
文摘In the rapidly evolving field of modern technology,near-infrared(NIR)photodetectors are extremely crucial for efficient and reliable optical communications.The graphene/GaAs Schottky junction photodetector leverages graphene’s exceptional carrier mobility and broadband absorption,coupled with GaAs’s strong absorption in the NIR spectrum,to achieve high responsivity and rapid response times.Here,we present a NIR photodetector employing a graphene/GaAs Schottky junction tailored for communication wavelengths.We fabricated high-performance graphene/GaAs Schottky junction devices with interdigitated electrodes of varying finger widths,systematically investigating their impact on device performance.The experimental results demonstrate that incorporating interdigitated electrodes significantly enhances the collection efficiency of photogenerated carriers in graphene/GaAs photodetectors.When illuminated by 808 nm NIR light at an intensity of 7.23 mW/cm^(2),the device achieves an impressive switch ratio of 10^(7),along with a high responsivity of 40.1 mA/W and a remarkable detectivity of 2.89×10^(13)Jones.Additionally,the device is characterized by rapid response times,with rise and fall times of 18.5 and 17.5μs,respectively,at a 3 dB bandwidth.These findings underscore the significant potential of high-performance graphene/GaAs photodetectors for applications in NIR optoelectronic systems.
文摘BACKGROUND Congenital junctional ectopic tachycardia(CJET)is a rare but life-threatening arrhythmia in neonates and infants,often refractory to conventional antiar-rhythmic therapy.Ivabradine,a selective inhibitor of hyperpolarization-activated cyclic nucleotide-gated channels,has emerged as a promising drug for CJET management.AIM To evaluate the efficacy and safety of ivabradine in the management of CJET.Specifically,this study aims to analyze the dosing strategies,treatment outcomes,and the role of ivabradine as monotherapy or adjunct therapy in patients who have previously received other antiarrhythmic medications.Additionally,this review seeks to assess the impact of ivabradine on heart rate(HR)control,rhythm conversion,and its overall safety profile to provide evidence-based insights into its clinical use for CJET management.METHODS This systematic review aims to evaluate the outcomes of ivabradine,either as monotherapy or as an adjunctive therapy,in the treatment of CJET.A compre-hensive literature search was conducted across multiple electronic databases to identify relevant studies investigating the use of ivabradine in CJET.Stringent inclusion and exclusion criteria were applied to ensure the inclusion of high-quality,peer-reviewed studies.Data extraction and quality assessment were performed independently by two reviewers.RESULTS Ten studies,comprising 6 case reports,3 case series,and 1 cohort study,met the inclusion criteria.Ivabradine doses ranged from 0.025 to 0.28 mg/kg/dose,administered either as monotherapy or in combination with various antiar-rhythmic medications.Overall,ivabradine demonstrated promising results in achieving HR control,conversion to sinus rhythm,or stabilization of junctional rhythm.No significant adverse effects related to ivabradine were reported.CONCLUSION The available evidence suggests that ivabradine may be an effective adjunctive therapy or,in some cases,a potential monotherapy for the management of CJET,particularly in cases refractory to traditional antiarrhythmic medications.However,the current evidence is limited by the small sample sizes and retrospective nature of the included studies.Well-designed prospective studies with larger cohorts and longer follow-up periods are warranted to further elucidate the role of ivabradine in CJET management.
基金The Natural Science Foundation of Guangdong Province(Project No.2023A1515012352)。
文摘Zinc oxide(ZnO),as a broadband gap semiconductor material,exhibits unique physical and chemical properties that make it highly suitable for optoelectronics,piezoelectric devices,and gas-sensitive sensors,showing significant potential for various applications.This paper focuses on the regulation and application of ZnO-based p-n junctions and piezoelectric devices.It discusses in detail the preparation of ZnO materials,the construction of p-n junctions,the optimization of piezoelectric device performance,and its application in various fields.By employing different preparation methods and strategies,high-quality ZnO thin films can be grown,and effective control of p-type conductivity achieved.This study provides both a theoretical foundation and technical support for controlling the performance of ZnO-based piezoelectric devices,as well as paving new pathways for the broader application of ZnO materials.
