在过去的二十年里,随着IMiD和indisulam等MG降解剂的出现,分子胶(MGs)逐渐引起了制药界的关注。这些分子通过促进靶蛋白和E3连接酶之间的相互作用来降解靶蛋白。此外,MGs作为化学诱导剂,促进同源蛋白和异源蛋白的二聚化形成三元复合物,...在过去的二十年里,随着IMiD和indisulam等MG降解剂的出现,分子胶(MGs)逐渐引起了制药界的关注。这些分子通过促进靶蛋白和E3连接酶之间的相互作用来降解靶蛋白。此外,MGs作为化学诱导剂,促进同源蛋白和异源蛋白的二聚化形成三元复合物,在调节生物活性方面具有很大的前景。本文重点介绍MGs在药物开发领域的应用,包括蛋白质–蛋白质相互作用(PPI)稳定性和蛋白质降解。我们深入分析了各种MGs的结构以及MGs与各种生物活性分子之间的相互作用,从而为PPI稳定剂和新型降解剂的开发提供了新的视角。Over the past two decades, molecular glues (MGs) have gradually attracted the attention of the pharmaceutical community with the advent of MG degraders such as IMiDs and indisulam. Such molecules degrade the target protein by promoting the interaction between the target protein and E3 ligase. In addition, as a chemical inducer, MGs promote the dimerization of homologous proteins and heterologous proteins to form ternary complexes, which have great prospects in regulating biological activities. This review focuses on the application of MGs in the field of drug development including protein-protein interaction (PPI) stability and protein degradation. We thoroughly analyze the structure of various MGs and the interactions between MGs and various biologically active molecules, thus providing new perspectives for the development of PPI stabilizers and new degraders.展开更多
Hypertension, often called the “silent killer”, is a major risk factor for heart attacks and strokes in the elderly. Its effective management is crucial to prevent damage to the heart, brain, and kidneys. Isolated s...Hypertension, often called the “silent killer”, is a major risk factor for heart attacks and strokes in the elderly. Its effective management is crucial to prevent damage to the heart, brain, and kidneys. Isolated systolic hypertension (ISH) is particularly critical in the elderly population. Cardiovascular risk factors, including pulse pressure and wave velocity, are closely associated with systolic blood pressure and influenced by arterial stiffness and wave reflections. Managing ISH is complex due to the potential negative effects of certain medications and individual variability in treatment response. This paper will address these issues, evaluating antihypertensive drugs, combination therapy, personalized treatment plans, and updated guidelines for managing ISH.展开更多
Objective:This study investigated the outcomes of microsurgical subinguinal varicocelectomy(MSV)on semen and hormonal parameters in cases with isolated sperm defects(oligozoospermia,asthenozoospermia,or teratozoosperm...Objective:This study investigated the outcomes of microsurgical subinguinal varicocelectomy(MSV)on semen and hormonal parameters in cases with isolated sperm defects(oligozoospermia,asthenozoospermia,or teratozoospermia).Methods:A retrospective review of charts of patients who underwent MSV for clinically palpable varicocele between January 1,2011 and January 1,2019 at Hamad Medical Corporation was undertaken.All patients diagnosed with isolated oligozoospermia,asthenozoospermia,or teratozoospermia in the preoperative semen analysis were included.Men with multiple sperm defects,genetic abnormalities,azoospermia,history of genitourinary infection,exposure to chemotherapy or radiotherapy,or prior use of peri-operative fertility treatment were excluded.Data extracted from the electronic medical records included(collected before MSV and up to 6 months postoperatively):demographics(age),clinical data(fertility-related medical history and surgical interventions),family history(consanguinity and infertility),physical examination findings from general and local genital exam(varicocele side and grade),laboratory data such as semen analysis,sperm DNA fragmentation tests,and hormone levels(follicle-stimulating hormone,luteinizing hormone,total testosterone,estradiol,and prolactin),and imaging(scrotal color Doppler ultrasound).Results:A total of 331 patients with isolated sperm defects were included.Postoperatively,83.3%of patients showed an improvement in sperm concentration with a median increase of 7 millions/mL.Postoperatively,76.7%of isolated asthenozoospermic patients showed an improvement in total motility and 66.0%had an improvement in progressive motility with median increases of 15.0%and 7.5%,respectively.Postoperatively,70.0%of the teratozoospermic patients showed an improvement in normal sperm morphology with a median increase of 6%.No changes were observed in other semen or hormone parameters that were examined.Conclusion:MSV is a valid and effective treatment modality for patients with isolated sperm defects that significantly corrects their respective semen abnormality and improves their chances of natural conception.展开更多
Isolated power converters have emerged as an active research topic in power integrated circuit(IC)design.Reflecting this growing interest,ISSCC 2025 has featured a dedicated session on"Isolated Power and Gate Dri...Isolated power converters have emerged as an active research topic in power integrated circuit(IC)design.Reflecting this growing interest,ISSCC 2025 has featured a dedicated session on"Isolated Power and Gate Drivers".These converters enable safe and reliable power delivery across voltage domains and are widely used in renewable energy,electric vehicles,and telecommunications.Galvanic isolation prevents surge currents and ground loop issues in harsh high-voltage environments.As demand grows for compact,efficient,and high–power-density solutions,fully integrated architectures featuring on-chip transformers are increasingly favored over traditional module-based designs,offering>5 kV isolation with a smaller footprint and lower system cost[1].展开更多
The present study investigates the influence of embedment depth of isolated footing supporting moment-resisting frame buildings through scaled-down tests.These experiments utilize scaled models representing different ...The present study investigates the influence of embedment depth of isolated footing supporting moment-resisting frame buildings through scaled-down tests.These experiments utilize scaled models representing different building aspect ratios and footing embedment depths.All the model tests are subjected to scaled-down input ground motions of different intensities and magnitudes.These model tests are performed in laminar shear containers through shake table testing.The results obtained for different cases of soil-foundation-structure systems and fixed-base conditions are expressed in terms of natural frequency,peak spectral acceleration,frequency response,lateral deformation,inter-storey drifts,and rocking of the foundation.The analysis reveals that the natural frequency of the coupled system on isolated footings diminishes by 27.52%–58.21%relative to fixed-base conditions,highlighting the significance of accounting for soil-foundation-structure interaction effects.Moreover,a notable increase of 52.97%in the natural frequency of the coupled system is observed as the embedment depth of the footing increases from 0.75 to 6.Additionally,the study demonstrates that the inter-storey drift of the 5-storey building remains well within acceptable limits under dense soil conditions.Consequently,within the parameter range explored in this research,the study concludes that soil-foundation-structure interaction effects are insignificant for low-rise buildings(H≤15 m)supported on isolated footings during seismic events.展开更多
In 2013,peste des petits ruminants(PPR)re-emerged in China and spread to the majority of provinces across the country.The disease was effectively controlled through a vaccination campaign employing live attenuated vac...In 2013,peste des petits ruminants(PPR)re-emerged in China and spread to the majority of provinces across the country.The disease was effectively controlled through a vaccination campaign employing live attenuated vaccines,although sporadic cases still occurred.However,limited information is currently available regarding the peste des petits ruminants virus(PPRV)endemic in China.Here,a PPRV strain(HLJ/13)was isolated from a field sample in China using Vero cells expressing goat signalling lymphocyte activation molecule.Phylogenetic analysis indicated that HLJ/13 belonged to lineage IV.Subsequent intranasal and subcutaneous inoculation of goats with a dose of 2×10~6 TCID50of HLJ/13 resulted in the development of typical clinical symptoms of PPR,including pyrexia,ocular and nasal discharges,stomatitis,and diarrhea.All infected goats succumbed to the disease by day 8.To gain further insight,viral loading,pathological examination and immunohistochemical analyses were conducted,elucidating the main targets of HLJ/13 as the respiratory system,digestive tract and lymphoid organs.Employing the goat infection model established above,the goat poxvirus-vectored PPR vaccine,which was previously developed and could be used as DIVA(differentiating infected from vaccinated animals)vaccine,provided complete protection against the challenge of HLJ/13.It is important to note that this study represents the first comprehensive report delineating the biology and pathogenicity characterization,and infection model of PPRV isolated in China.展开更多
Finding an optimal isolator arrangement for asymmetric structures using traditional conceptual design methods that can significantly minimize torsional response while ensuring efficient horizontal seismic isolation is...Finding an optimal isolator arrangement for asymmetric structures using traditional conceptual design methods that can significantly minimize torsional response while ensuring efficient horizontal seismic isolation is cumbersome and inefficient.Thus,this work develops a multi-objective optimization method to enhance the torsional resistance of asymmetric base-isolated structures.The primary objective is to simultaneously minimize the interstory rotation of the superstructure,the rotation of the isolation layer,and the interstory displacement of the superstructure without exceeding the isolator displacement limits.A fast non-dominated sorting genetic algorithm(NSGA-Ⅱ)is employed to satisfy this optimization objective.Subsequently,the isolator arrangement,encompassing both positions and categories,is optimized according to this multi-objective optimization method.Additionally,an optimization design platform is developed to streamline the design operation.This platform integrates the input of optimization parameters,the output of optimization results,the finite element analysis,and the multi-objective optimization method proposed herein.Finally,the application of this multi-objective optimization method and its associated platform are demonstrated on two asymmetric base-isolated structures of varying heights and plan configurations.The results indicate that the optimal isolator arrangement derived from the optimization method can further improve the control over the lateral and torsional responses of asymmetric base-isolated structures compared to conventional conceptual design methods.Notably,the interstory rotation of the optimal base-isolated structure is significantly reduced,constituting only approximately 33.7%of that observed in the original base-isolated structure.The proposed platform facilitates the automatic generation of the optimal design scheme for the isolators of asymmetric base-isolated structures,offering valuable insights and guidance for the burgeoning field of intelligent civil engineering design.展开更多
BACKGROUND Endoscopic healing(EH)is a key therapeutic target in Crohn’s disease(CD).Proximal small bowel(SB)lesions in patients with CD are associated with a significant risk of strictures and bowel resection.Assessi...BACKGROUND Endoscopic healing(EH)is a key therapeutic target in Crohn’s disease(CD).Proximal small bowel(SB)lesions in patients with CD are associated with a significant risk of strictures and bowel resection.Assessing SB in patients with CD is necessary because of its significant therapeutic implications.The advent of biologic therapies,including infliximab,ustekinumab,and vedolizumab,has significantly altered CD treatment.However,data on the efficacy of biologics in achieving EH,specifically in the proximal SB of patients with CD,remain limited.AIM To assess the effectiveness of biologics for EH in patients with jejunal and/or proximal ileal CD.METHODS Between 2017 and 2023,we retrospectively included 110 consecutive patients with isolated proximal SB CD,identified through baseline balloon-assisted enteroscopy.These patients completed 1-year of treatment with infliximab,ustekinumab,or vedolizumab,and underwent a second balloon-assisted enteroscopy at 1 year.Complete EH was defined as a modified Simple Endoscopic Score for CD(SES-CD)of<3,while EH of the jejunum and proximal ileum was defined as a segmental modified SES-CD of 0.RESULTS In total,64 patients were treated with infliximab,28 with ustekinumab,and 18 with vedolizumab.The complete EH rate at 1 year was 20.9%(23/110),with 29.6%(19/64)for infliximab,10.7%(3/28)for ustekinumab,and 5.5%(1/18)for vedolizumab.The median modified SES-CD significantly decreased compared to baseline[5(2-8)vs 8(6-9),P<0.001].The jejunal and proximal ileal EH rates at 1 year were 30.8%(12/39)and 15.5%(16/103),respectively.Multiple logistic regression analysis showed that stricturing or penetrating disease[odds ratio(OR)=0.261,95%CI:0.087-0.778,P=0.016],prior exposure to biologics(OR=0.080,95%CI:0.010-0.674,P=0.020),and moderate-tosevere endoscopic disease(OR=0.277,95%CI:0.093-0.829,P=0.022)were associated with a lower likelihood of achieving EH at 1 year.CONCLUSION Only 20.9%of patients with isolated proximal SB CD achieved complete EH after 1 year of biologic therapy.展开更多
By integrating core observations,logging data and seismic interpretation,this study takes the massive Cretaceous carbonates in the M block of the Santos Basin,Brazil,as an example to establish the sequence filling pat...By integrating core observations,logging data and seismic interpretation,this study takes the massive Cretaceous carbonates in the M block of the Santos Basin,Brazil,as an example to establish the sequence filling pattern of fault-bounded isolated platforms in rift lake basins,reveal the control mechanisms of shoal-body development and reservoir formation,and reconstruct the evolutionary history of lithofacies paleogeography.The following results are obtained.(1)Three tertiary sequences(SQ1-SQ3)are identified in the Lower Cretaceous Itapema-Barra Velha of the M block.During the depositional period of SQ1,the rift basement faults controlled the stratigraphic distribution pattern of thick on both sides and thin in the middle.The strata overlapped to uplift in the early stage.During the depositional period of SQ2-SQ3,the synsedimentary faults controlled the paleogeomorphic reworking process with subsidence in the northwest and uplifting in the northeast,accompanied with the relative fall of lake level.(2)The Lower Cretaceous in the M block was deposited in a littoral-shallow lake,with the lithofacies paleogeographic pattern transiting from the inner clastic shoals and outer shelly shoals in SQ1 to the alternation of mounds and shoals in SQ2-SQ3.(3)Under the joint control of relative lake-level fluctuation,synsedimentary faults and volcanic activity,the shelly shoals in SQ1 tend to accumulated vertically in the raised area,and the mound-shoal complex in SQ2-SQ3 tends to migrate laterally towards the slope-break belt due to the reduction of accommodation space.(4)The evolution pattern of high-energy mounds and shoals,which were vertically accumulated in the early stage and laterally migrated in the later stage,controlled the transformation of high-quality reservoirs from“centralized”to“ring shaped”distribution.The research findings clarify the sedimentary patterns of mounds and shoals and the distribution of favorable reservoirs in the fault-controlled lacustrine isolated platform,providing support for the deepwater hydrocarbon exploration in the subsalt carbonate rocks in the Santos Basin.展开更多
In this study,two series of foams based on tannic acid(TA),furfuryl alcohol(FA),soybean protein isolate(SPI),and casein(CA),namely TA–FA–SPI(TS series)and TA–FA–CA(TC series)were developed,and their properties wer...In this study,two series of foams based on tannic acid(TA),furfuryl alcohol(FA),soybean protein isolate(SPI),and casein(CA),namely TA–FA–SPI(TS series)and TA–FA–CA(TC series)were developed,and their properties were enhanced by adding poplar fibers(WF).From the samples produced,a complete set of characterization was performed including possible crosslinking reactions,morphology,mechanical properties,flame retardancy,thermal insulation and thermal stability.Fourier-transform infrared spectroscopy(FTIR)revealed possible covalent crosslinking among the components and hydrogen bonding between WF and the matrix.Viscosity results indicated that lower prepolymer viscosity led to lower apparent density,while WF addition reduced even more the density.Mechanical tests showed that the maximum compressive strengths were good,while WF improved the compressive strength by up to 56%.Scanning electron microscopy(SEM)showed uniform cell structures,but small open pores were observed.Two-dimensional(2D)CT scan images confirmed the good compatibility between WF and the matrix,with low anisotropy in the material.Friability tests indicated that WF decreased the pulverization ratio of the materials by up to 42%.Thermogravimetric analysis(TGA)showed good thermal stability of the materials up to 328°C.Vertical burning tests showed that the materials were self-extinguishing without residue(dripping).The lowest thermal conductivity was 0.04 W/m·K.These results suggest that these novel formaldehyde-free,high biomass content(95%–96%)foams and composite foams have high potential to replace traditional phenolic foams(PF)in applications such as construction,transportation,packaging,and thermal insulation.展开更多
Acute respiratory tract infections(ARTIs)are among the leading causes of morbidity and mortality in children worldwide.Human adenovirus(HAdV)infections are estimated to account for at least 5%of pediatric ARTIs.The ci...Acute respiratory tract infections(ARTIs)are among the leading causes of morbidity and mortality in children worldwide.Human adenovirus(HAdV)infections are estimated to account for at least 5%of pediatric ARTIs.The circulated genotypes of HAdV and the correlation between genotype and clinical manifestations in Wuhan,China,before and after the complete relaxation of nonpharmaceutical interventions against severe acute respiratory syndrome coronavirus 2,remain unknown.Here,101 HAdV strains were isolated from throat swab samples collected from hospitalized children with ARTIs who tested positive for HAdV nucleic acid.Of these,sixty-six strains from 2022 to twenty-three strains from 2023 were successfully genotyped and subjected to phylogenetic analysis based on the hexon,penton base,and fiber genes.Six genotypes,B3,C1,C2,C5,C104,and C108 were identified.HAdV-B3(84.85%)was the most prevalent type in 2022,while HAdV-C(86.96%),including C1,C2,C108,and C104,was the most prevalent in 2023.These strains were phylogenetically related to strains from Japan,China,and the United States in recent years.When comparing clinical characteristics,pediatric patients infected with B3,C1,C2,C5,C104,or C108 exhibited similar clinical manifestations,primarily fever and cough,but varying interleukin(IL)-10 levels.In conclusion,from June 2022 to September 2023,the circulated genotypes of HAdV in Wuhan included B3,C1,C2,C108,C5,and C104.The endemic pattern of HAdV in Wuhan,China,shifted from species B as the dominant type in 2022 to species C in 2023.展开更多
Aortic regurgitation(AR)poses distinct challenges in interventional cardiology,necessitating novel approaches for treatment.This editorial examined the evolving landscape of transcatheter aortic valve replacement(TAVR...Aortic regurgitation(AR)poses distinct challenges in interventional cardiology,necessitating novel approaches for treatment.This editorial examined the evolving landscape of transcatheter aortic valve replacement(TAVR)as an alternative therapeutic strategy for AR,particularly in patients deemed high risk for surgery.We explored the anatomical and patho-physiological disparities between AR and aortic stenosis(AS)and elucidates the technical nuances of TAVR procedures in AR pa-tients,emphasizing the need for precise prosthesis positioning and considerations for excessive stroke volume.Additionally,we discussed the safety and efficacy of TAVR compared to SAVR in AR management,drawing insights from recent case series and registry data.Notably,dedicated TAVR devices tailored for AR,such as the J-Valve and JenaValve,demonstrate promising out-comes in reducing residual AR and ensuring procedural success.Conversely,“off-label”TAVR devices,including balloon-ex-pandable and self-expandable platforms,offer feasible alternatives-particularly for large aortic annuli-with favorable device suc-cess rates and low residual AR rates.We highlighted the need for further research,including randomized trials,to delineate the definitive role of TAVR in AR treatment and to address remaining questions regarding device selection and long-term outcomes.In conclusion,TAVR emerges as a viable option for patients with AR,particularly those facing high surgical risks or frailty,with ongoing investigations poised to refine its position in the therapeutic armamentarium.展开更多
In response to the problems of unclear distribution of deep-water pre-salt carbonate reservoirs and formation conditions of large oil fields in the Santos passive continental margin basin,based on comprehensive utiliz...In response to the problems of unclear distribution of deep-water pre-salt carbonate reservoirs and formation conditions of large oil fields in the Santos passive continental margin basin,based on comprehensive utilization of geological,seismic,and core data,and reconstruction of Early Cretaceous prototype basin and lithofacies paleogeography,it is proposed for the first time that the construction of pre-salt carbonate build-ups was controlled by two types of isolated platforms:inter-depression fault-uplift and intra-depression fault-high.The inter-depression fault-uplift isolated platforms are distributed on the present-day pre-salt uplifted zones between depressions,and are built on half-and fault-horst blocks that were inherited and developed in the early intra-continental and inter-continental rift stages.The late intra-continental rift coquinas of the ITP Formation and the early inter-continental rift microbial limestones of the BVE Formation are continuously constructed;intra-depression fault-high isolated platforms are distributed in the current pre-salt depression zones,built on the uplifted zones formed by volcanic rock build-ups in the early prototype stage of intra-continental rifts,and only the BVE microbial limestones are developed.Both types of limestones formed into mound-shoal bodies,that have the characteristics of large reservoir thickness and good physical properties.Based on the dissection of large pre-salt oil fields discovered in the Santos Basin,it has been found that both types of platforms could form large-scale combined structural-stratigraphic traps,surrounded by high-quality lacustrine and lagoon source rocks at the periphery,and efficiently sealed by thick high-quality evaporite rocks above,forming the optimal combination of source,reservoir and cap in the form of“lower generation,middle storage,and upper cap”,with a high degree of oil and gas enrichment.It has been found that the large oil fields are all bottom water massive oil fields with a unified pressure system,and they are all filled to the spill-point.The future exploration is recommended to focus on the inter-depression fault-uplift isolated platforms in the western uplift zone and the southern section of eastern uplift zones,as well as intra-depression fault-high isolated platforms in the central depression zone.The result not only provides an important basis for the advanced selection of potential play fairways,bidding of new blocks,and deployment of awarded exploration blocks in the Santos Basin,but also provides a reference for the global selection of deep-water exploration blocks in passive continental margin basins.展开更多
At present,there is not much research on mid-story isolated structures in mountainous areas.In this study,a model of a mid-story isolated structure considering soil-structure interaction(SSI)in mountainous areas is es...At present,there is not much research on mid-story isolated structures in mountainous areas.In this study,a model of a mid-story isolated structure considering soil-structure interaction(SSI)in mountainous areas is established along with a model that does not consider SSI.Eight long-period earthquake waves and two ordinary earthquake waves are selected as inputs for the dynamic time history analysis of the structure.The results show that the seismic response of a mid-story isolated structure considering SSI in mountainous areas can be amplified when compared with a structure that does not consider SSI.The structure response under long-period earthquakes is larger than that of ordinary earthquakes.The structure response under far-field harmonic-like earthquakes is larger than that of near-fault pulse-type earthquakes.The structure response under near-fault pulse-type earthquakes is larger than that of far-field non-harmonic earthquakes.When subjected to long-period earthquakes,the displacement of the isolated bearings exceeded the limit value,which led to instability and overturning of the structure.The structure with dampers in the isolated story could adequately control the nonlinear response of the structure,effectively reduce the displacement of the isolated bearings,and provide a convenient,efficient and economic method not only for new construction but also to retrofit existing structures.展开更多
文摘在过去的二十年里,随着IMiD和indisulam等MG降解剂的出现,分子胶(MGs)逐渐引起了制药界的关注。这些分子通过促进靶蛋白和E3连接酶之间的相互作用来降解靶蛋白。此外,MGs作为化学诱导剂,促进同源蛋白和异源蛋白的二聚化形成三元复合物,在调节生物活性方面具有很大的前景。本文重点介绍MGs在药物开发领域的应用,包括蛋白质–蛋白质相互作用(PPI)稳定性和蛋白质降解。我们深入分析了各种MGs的结构以及MGs与各种生物活性分子之间的相互作用,从而为PPI稳定剂和新型降解剂的开发提供了新的视角。Over the past two decades, molecular glues (MGs) have gradually attracted the attention of the pharmaceutical community with the advent of MG degraders such as IMiDs and indisulam. Such molecules degrade the target protein by promoting the interaction between the target protein and E3 ligase. In addition, as a chemical inducer, MGs promote the dimerization of homologous proteins and heterologous proteins to form ternary complexes, which have great prospects in regulating biological activities. This review focuses on the application of MGs in the field of drug development including protein-protein interaction (PPI) stability and protein degradation. We thoroughly analyze the structure of various MGs and the interactions between MGs and various biologically active molecules, thus providing new perspectives for the development of PPI stabilizers and new degraders.
文摘Hypertension, often called the “silent killer”, is a major risk factor for heart attacks and strokes in the elderly. Its effective management is crucial to prevent damage to the heart, brain, and kidneys. Isolated systolic hypertension (ISH) is particularly critical in the elderly population. Cardiovascular risk factors, including pulse pressure and wave velocity, are closely associated with systolic blood pressure and influenced by arterial stiffness and wave reflections. Managing ISH is complex due to the potential negative effects of certain medications and individual variability in treatment response. This paper will address these issues, evaluating antihypertensive drugs, combination therapy, personalized treatment plans, and updated guidelines for managing ISH.
文摘Objective:This study investigated the outcomes of microsurgical subinguinal varicocelectomy(MSV)on semen and hormonal parameters in cases with isolated sperm defects(oligozoospermia,asthenozoospermia,or teratozoospermia).Methods:A retrospective review of charts of patients who underwent MSV for clinically palpable varicocele between January 1,2011 and January 1,2019 at Hamad Medical Corporation was undertaken.All patients diagnosed with isolated oligozoospermia,asthenozoospermia,or teratozoospermia in the preoperative semen analysis were included.Men with multiple sperm defects,genetic abnormalities,azoospermia,history of genitourinary infection,exposure to chemotherapy or radiotherapy,or prior use of peri-operative fertility treatment were excluded.Data extracted from the electronic medical records included(collected before MSV and up to 6 months postoperatively):demographics(age),clinical data(fertility-related medical history and surgical interventions),family history(consanguinity and infertility),physical examination findings from general and local genital exam(varicocele side and grade),laboratory data such as semen analysis,sperm DNA fragmentation tests,and hormone levels(follicle-stimulating hormone,luteinizing hormone,total testosterone,estradiol,and prolactin),and imaging(scrotal color Doppler ultrasound).Results:A total of 331 patients with isolated sperm defects were included.Postoperatively,83.3%of patients showed an improvement in sperm concentration with a median increase of 7 millions/mL.Postoperatively,76.7%of isolated asthenozoospermic patients showed an improvement in total motility and 66.0%had an improvement in progressive motility with median increases of 15.0%and 7.5%,respectively.Postoperatively,70.0%of the teratozoospermic patients showed an improvement in normal sperm morphology with a median increase of 6%.No changes were observed in other semen or hormone parameters that were examined.Conclusion:MSV is a valid and effective treatment modality for patients with isolated sperm defects that significantly corrects their respective semen abnormality and improves their chances of natural conception.
基金supported in part by the National Natural Science Foundation of China under Grant U23A20353.
文摘Isolated power converters have emerged as an active research topic in power integrated circuit(IC)design.Reflecting this growing interest,ISSCC 2025 has featured a dedicated session on"Isolated Power and Gate Drivers".These converters enable safe and reliable power delivery across voltage domains and are widely used in renewable energy,electric vehicles,and telecommunications.Galvanic isolation prevents surge currents and ground loop issues in harsh high-voltage environments.As demand grows for compact,efficient,and high–power-density solutions,fully integrated architectures featuring on-chip transformers are increasingly favored over traditional module-based designs,offering>5 kV isolation with a smaller footprint and lower system cost[1].
基金fellowship received from the Department of Science and Technology(DST)under a unique scheme,“Innovation in Science Pursuit for Inspired Research(INSPIRE),”under the file number 20190000871,during the present work。
文摘The present study investigates the influence of embedment depth of isolated footing supporting moment-resisting frame buildings through scaled-down tests.These experiments utilize scaled models representing different building aspect ratios and footing embedment depths.All the model tests are subjected to scaled-down input ground motions of different intensities and magnitudes.These model tests are performed in laminar shear containers through shake table testing.The results obtained for different cases of soil-foundation-structure systems and fixed-base conditions are expressed in terms of natural frequency,peak spectral acceleration,frequency response,lateral deformation,inter-storey drifts,and rocking of the foundation.The analysis reveals that the natural frequency of the coupled system on isolated footings diminishes by 27.52%–58.21%relative to fixed-base conditions,highlighting the significance of accounting for soil-foundation-structure interaction effects.Moreover,a notable increase of 52.97%in the natural frequency of the coupled system is observed as the embedment depth of the footing increases from 0.75 to 6.Additionally,the study demonstrates that the inter-storey drift of the 5-storey building remains well within acceptable limits under dense soil conditions.Consequently,within the parameter range explored in this research,the study concludes that soil-foundation-structure interaction effects are insignificant for low-rise buildings(H≤15 m)supported on isolated footings during seismic events.
基金supported by the National Key Research and Development Program of China(2016YFD0500108)the International S&T Cooperation Program of China(ISTCP)(2015DFA31300)。
文摘In 2013,peste des petits ruminants(PPR)re-emerged in China and spread to the majority of provinces across the country.The disease was effectively controlled through a vaccination campaign employing live attenuated vaccines,although sporadic cases still occurred.However,limited information is currently available regarding the peste des petits ruminants virus(PPRV)endemic in China.Here,a PPRV strain(HLJ/13)was isolated from a field sample in China using Vero cells expressing goat signalling lymphocyte activation molecule.Phylogenetic analysis indicated that HLJ/13 belonged to lineage IV.Subsequent intranasal and subcutaneous inoculation of goats with a dose of 2×10~6 TCID50of HLJ/13 resulted in the development of typical clinical symptoms of PPR,including pyrexia,ocular and nasal discharges,stomatitis,and diarrhea.All infected goats succumbed to the disease by day 8.To gain further insight,viral loading,pathological examination and immunohistochemical analyses were conducted,elucidating the main targets of HLJ/13 as the respiratory system,digestive tract and lymphoid organs.Employing the goat infection model established above,the goat poxvirus-vectored PPR vaccine,which was previously developed and could be used as DIVA(differentiating infected from vaccinated animals)vaccine,provided complete protection against the challenge of HLJ/13.It is important to note that this study represents the first comprehensive report delineating the biology and pathogenicity characterization,and infection model of PPRV isolated in China.
基金National Natural Science Foundation of China under Grant No.52278490。
文摘Finding an optimal isolator arrangement for asymmetric structures using traditional conceptual design methods that can significantly minimize torsional response while ensuring efficient horizontal seismic isolation is cumbersome and inefficient.Thus,this work develops a multi-objective optimization method to enhance the torsional resistance of asymmetric base-isolated structures.The primary objective is to simultaneously minimize the interstory rotation of the superstructure,the rotation of the isolation layer,and the interstory displacement of the superstructure without exceeding the isolator displacement limits.A fast non-dominated sorting genetic algorithm(NSGA-Ⅱ)is employed to satisfy this optimization objective.Subsequently,the isolator arrangement,encompassing both positions and categories,is optimized according to this multi-objective optimization method.Additionally,an optimization design platform is developed to streamline the design operation.This platform integrates the input of optimization parameters,the output of optimization results,the finite element analysis,and the multi-objective optimization method proposed herein.Finally,the application of this multi-objective optimization method and its associated platform are demonstrated on two asymmetric base-isolated structures of varying heights and plan configurations.The results indicate that the optimal isolator arrangement derived from the optimization method can further improve the control over the lateral and torsional responses of asymmetric base-isolated structures compared to conventional conceptual design methods.Notably,the interstory rotation of the optimal base-isolated structure is significantly reduced,constituting only approximately 33.7%of that observed in the original base-isolated structure.The proposed platform facilitates the automatic generation of the optimal design scheme for the isolators of asymmetric base-isolated structures,offering valuable insights and guidance for the burgeoning field of intelligent civil engineering design.
基金Supported by the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND Endoscopic healing(EH)is a key therapeutic target in Crohn’s disease(CD).Proximal small bowel(SB)lesions in patients with CD are associated with a significant risk of strictures and bowel resection.Assessing SB in patients with CD is necessary because of its significant therapeutic implications.The advent of biologic therapies,including infliximab,ustekinumab,and vedolizumab,has significantly altered CD treatment.However,data on the efficacy of biologics in achieving EH,specifically in the proximal SB of patients with CD,remain limited.AIM To assess the effectiveness of biologics for EH in patients with jejunal and/or proximal ileal CD.METHODS Between 2017 and 2023,we retrospectively included 110 consecutive patients with isolated proximal SB CD,identified through baseline balloon-assisted enteroscopy.These patients completed 1-year of treatment with infliximab,ustekinumab,or vedolizumab,and underwent a second balloon-assisted enteroscopy at 1 year.Complete EH was defined as a modified Simple Endoscopic Score for CD(SES-CD)of<3,while EH of the jejunum and proximal ileum was defined as a segmental modified SES-CD of 0.RESULTS In total,64 patients were treated with infliximab,28 with ustekinumab,and 18 with vedolizumab.The complete EH rate at 1 year was 20.9%(23/110),with 29.6%(19/64)for infliximab,10.7%(3/28)for ustekinumab,and 5.5%(1/18)for vedolizumab.The median modified SES-CD significantly decreased compared to baseline[5(2-8)vs 8(6-9),P<0.001].The jejunal and proximal ileal EH rates at 1 year were 30.8%(12/39)and 15.5%(16/103),respectively.Multiple logistic regression analysis showed that stricturing or penetrating disease[odds ratio(OR)=0.261,95%CI:0.087-0.778,P=0.016],prior exposure to biologics(OR=0.080,95%CI:0.010-0.674,P=0.020),and moderate-tosevere endoscopic disease(OR=0.277,95%CI:0.093-0.829,P=0.022)were associated with a lower likelihood of achieving EH at 1 year.CONCLUSION Only 20.9%of patients with isolated proximal SB CD achieved complete EH after 1 year of biologic therapy.
基金Supported by the China National Science and Technology Major Project(2025ZD1403000)CNPC Major Science and Technology Project(2023ZZ19).
文摘By integrating core observations,logging data and seismic interpretation,this study takes the massive Cretaceous carbonates in the M block of the Santos Basin,Brazil,as an example to establish the sequence filling pattern of fault-bounded isolated platforms in rift lake basins,reveal the control mechanisms of shoal-body development and reservoir formation,and reconstruct the evolutionary history of lithofacies paleogeography.The following results are obtained.(1)Three tertiary sequences(SQ1-SQ3)are identified in the Lower Cretaceous Itapema-Barra Velha of the M block.During the depositional period of SQ1,the rift basement faults controlled the stratigraphic distribution pattern of thick on both sides and thin in the middle.The strata overlapped to uplift in the early stage.During the depositional period of SQ2-SQ3,the synsedimentary faults controlled the paleogeomorphic reworking process with subsidence in the northwest and uplifting in the northeast,accompanied with the relative fall of lake level.(2)The Lower Cretaceous in the M block was deposited in a littoral-shallow lake,with the lithofacies paleogeographic pattern transiting from the inner clastic shoals and outer shelly shoals in SQ1 to the alternation of mounds and shoals in SQ2-SQ3.(3)Under the joint control of relative lake-level fluctuation,synsedimentary faults and volcanic activity,the shelly shoals in SQ1 tend to accumulated vertically in the raised area,and the mound-shoal complex in SQ2-SQ3 tends to migrate laterally towards the slope-break belt due to the reduction of accommodation space.(4)The evolution pattern of high-energy mounds and shoals,which were vertically accumulated in the early stage and laterally migrated in the later stage,controlled the transformation of high-quality reservoirs from“centralized”to“ring shaped”distribution.The research findings clarify the sedimentary patterns of mounds and shoals and the distribution of favorable reservoirs in the fault-controlled lacustrine isolated platform,providing support for the deepwater hydrocarbon exploration in the subsalt carbonate rocks in the Santos Basin.
基金funded by the Natural Sciences and Engineering Research Council of Canada(NSERC)for financial support,Grant Nos.CG125664 and GF136078.
文摘In this study,two series of foams based on tannic acid(TA),furfuryl alcohol(FA),soybean protein isolate(SPI),and casein(CA),namely TA–FA–SPI(TS series)and TA–FA–CA(TC series)were developed,and their properties were enhanced by adding poplar fibers(WF).From the samples produced,a complete set of characterization was performed including possible crosslinking reactions,morphology,mechanical properties,flame retardancy,thermal insulation and thermal stability.Fourier-transform infrared spectroscopy(FTIR)revealed possible covalent crosslinking among the components and hydrogen bonding between WF and the matrix.Viscosity results indicated that lower prepolymer viscosity led to lower apparent density,while WF addition reduced even more the density.Mechanical tests showed that the maximum compressive strengths were good,while WF improved the compressive strength by up to 56%.Scanning electron microscopy(SEM)showed uniform cell structures,but small open pores were observed.Two-dimensional(2D)CT scan images confirmed the good compatibility between WF and the matrix,with low anisotropy in the material.Friability tests indicated that WF decreased the pulverization ratio of the materials by up to 42%.Thermogravimetric analysis(TGA)showed good thermal stability of the materials up to 328°C.Vertical burning tests showed that the materials were self-extinguishing without residue(dripping).The lowest thermal conductivity was 0.04 W/m·K.These results suggest that these novel formaldehyde-free,high biomass content(95%–96%)foams and composite foams have high potential to replace traditional phenolic foams(PF)in applications such as construction,transportation,packaging,and thermal insulation.
基金supported by the projects of National Virus Resource Center(NVRC-PY-03,E1YZ020501)Natural Science Foundation of Hubei Province(2022CFB564)+4 种基金Foundation of Hubei Provincial Health Commission(WJ2023M108)National Basic Science Data Sharing Platform(no.2018ZX10101004)National Basic Science Data Sharing Service Platform(no.NBSDC-DB-13)the International Cooperation Base of Hubei Province for Infection and Immunitysupported by Outstanding Medical Young Scholars of Hubei Province and Wuhan Young and Middle-aged Medical Backbone Talent Program.
文摘Acute respiratory tract infections(ARTIs)are among the leading causes of morbidity and mortality in children worldwide.Human adenovirus(HAdV)infections are estimated to account for at least 5%of pediatric ARTIs.The circulated genotypes of HAdV and the correlation between genotype and clinical manifestations in Wuhan,China,before and after the complete relaxation of nonpharmaceutical interventions against severe acute respiratory syndrome coronavirus 2,remain unknown.Here,101 HAdV strains were isolated from throat swab samples collected from hospitalized children with ARTIs who tested positive for HAdV nucleic acid.Of these,sixty-six strains from 2022 to twenty-three strains from 2023 were successfully genotyped and subjected to phylogenetic analysis based on the hexon,penton base,and fiber genes.Six genotypes,B3,C1,C2,C5,C104,and C108 were identified.HAdV-B3(84.85%)was the most prevalent type in 2022,while HAdV-C(86.96%),including C1,C2,C108,and C104,was the most prevalent in 2023.These strains were phylogenetically related to strains from Japan,China,and the United States in recent years.When comparing clinical characteristics,pediatric patients infected with B3,C1,C2,C5,C104,or C108 exhibited similar clinical manifestations,primarily fever and cough,but varying interleukin(IL)-10 levels.In conclusion,from June 2022 to September 2023,the circulated genotypes of HAdV in Wuhan included B3,C1,C2,C108,C5,and C104.The endemic pattern of HAdV in Wuhan,China,shifted from species B as the dominant type in 2022 to species C in 2023.
文摘Aortic regurgitation(AR)poses distinct challenges in interventional cardiology,necessitating novel approaches for treatment.This editorial examined the evolving landscape of transcatheter aortic valve replacement(TAVR)as an alternative therapeutic strategy for AR,particularly in patients deemed high risk for surgery.We explored the anatomical and patho-physiological disparities between AR and aortic stenosis(AS)and elucidates the technical nuances of TAVR procedures in AR pa-tients,emphasizing the need for precise prosthesis positioning and considerations for excessive stroke volume.Additionally,we discussed the safety and efficacy of TAVR compared to SAVR in AR management,drawing insights from recent case series and registry data.Notably,dedicated TAVR devices tailored for AR,such as the J-Valve and JenaValve,demonstrate promising out-comes in reducing residual AR and ensuring procedural success.Conversely,“off-label”TAVR devices,including balloon-ex-pandable and self-expandable platforms,offer feasible alternatives-particularly for large aortic annuli-with favorable device suc-cess rates and low residual AR rates.We highlighted the need for further research,including randomized trials,to delineate the definitive role of TAVR in AR treatment and to address remaining questions regarding device selection and long-term outcomes.In conclusion,TAVR emerges as a viable option for patients with AR,particularly those facing high surgical risks or frailty,with ongoing investigations poised to refine its position in the therapeutic armamentarium.
基金Supported by the National Science and Technology Major Project(2016ZX05029001)CNPC Science and Technology Project(2019D-4310)。
文摘In response to the problems of unclear distribution of deep-water pre-salt carbonate reservoirs and formation conditions of large oil fields in the Santos passive continental margin basin,based on comprehensive utilization of geological,seismic,and core data,and reconstruction of Early Cretaceous prototype basin and lithofacies paleogeography,it is proposed for the first time that the construction of pre-salt carbonate build-ups was controlled by two types of isolated platforms:inter-depression fault-uplift and intra-depression fault-high.The inter-depression fault-uplift isolated platforms are distributed on the present-day pre-salt uplifted zones between depressions,and are built on half-and fault-horst blocks that were inherited and developed in the early intra-continental and inter-continental rift stages.The late intra-continental rift coquinas of the ITP Formation and the early inter-continental rift microbial limestones of the BVE Formation are continuously constructed;intra-depression fault-high isolated platforms are distributed in the current pre-salt depression zones,built on the uplifted zones formed by volcanic rock build-ups in the early prototype stage of intra-continental rifts,and only the BVE microbial limestones are developed.Both types of limestones formed into mound-shoal bodies,that have the characteristics of large reservoir thickness and good physical properties.Based on the dissection of large pre-salt oil fields discovered in the Santos Basin,it has been found that both types of platforms could form large-scale combined structural-stratigraphic traps,surrounded by high-quality lacustrine and lagoon source rocks at the periphery,and efficiently sealed by thick high-quality evaporite rocks above,forming the optimal combination of source,reservoir and cap in the form of“lower generation,middle storage,and upper cap”,with a high degree of oil and gas enrichment.It has been found that the large oil fields are all bottom water massive oil fields with a unified pressure system,and they are all filled to the spill-point.The future exploration is recommended to focus on the inter-depression fault-uplift isolated platforms in the western uplift zone and the southern section of eastern uplift zones,as well as intra-depression fault-high isolated platforms in the central depression zone.The result not only provides an important basis for the advanced selection of potential play fairways,bidding of new blocks,and deployment of awarded exploration blocks in the Santos Basin,but also provides a reference for the global selection of deep-water exploration blocks in passive continental margin basins.
基金National Natural Science Fund of China under Nos.52168072 and 51808467High-level Talents Support Plan of Yunnan Province of China(2020)。
文摘At present,there is not much research on mid-story isolated structures in mountainous areas.In this study,a model of a mid-story isolated structure considering soil-structure interaction(SSI)in mountainous areas is established along with a model that does not consider SSI.Eight long-period earthquake waves and two ordinary earthquake waves are selected as inputs for the dynamic time history analysis of the structure.The results show that the seismic response of a mid-story isolated structure considering SSI in mountainous areas can be amplified when compared with a structure that does not consider SSI.The structure response under long-period earthquakes is larger than that of ordinary earthquakes.The structure response under far-field harmonic-like earthquakes is larger than that of near-fault pulse-type earthquakes.The structure response under near-fault pulse-type earthquakes is larger than that of far-field non-harmonic earthquakes.When subjected to long-period earthquakes,the displacement of the isolated bearings exceeded the limit value,which led to instability and overturning of the structure.The structure with dampers in the isolated story could adequately control the nonlinear response of the structure,effectively reduce the displacement of the isolated bearings,and provide a convenient,efficient and economic method not only for new construction but also to retrofit existing structures.
