This paper studies cooperative robust parallel operation of multiple actuators over an undirected communication graph.The plant is modeled as an uncertain linear system,and the actuators are linear and identical.Based...This paper studies cooperative robust parallel operation of multiple actuators over an undirected communication graph.The plant is modeled as an uncertain linear system,and the actuators are linear and identical.Based on the internal model principle,a distributed dynamic output feedback control law is proposed to achieve both robust output regulation of the closed-loop system and plant input sharing among the actuators.A practical example of five motors cooperatively driving an uncertain shaft under an external load torque is presented to show the effectiveness of the proposed control law.展开更多
To conduct marine surveys,multiple unmanned surface vessels(Multi-USV)with different capabilities perform collaborative mapping in multiple designated areas.This paper proposes a task allocation algorithm based on int...To conduct marine surveys,multiple unmanned surface vessels(Multi-USV)with different capabilities perform collaborative mapping in multiple designated areas.This paper proposes a task allocation algorithm based on integer linear programming(ILP)with flow balance constraints,ensuring the fair and efficient distribution of sub-areas among USVs and maintaining strong connectivity of assigned regions.In the established gridmap,a search-based path planning algorithm is performed on the sub-areas according to the allocation scheme.It uses the greedy algorithm and the A*algorithm to achieve complete coverage of the barrier-free area and obtain an efficient trajectory of each USV.The greedy algorithm enables fast local traversal of unvisited grids,while the A*algorithm ensures navigation to escape from deadlock areas and maintains global path continuity.The comparison of task allocation results proves that the task allocation algorithm based on ILP improves the mapping efficiency and task distribution fairness.The proposed allocation method and result analysis provide a certain reference for the practical application ofMulti-USV to perform survey tasks collaboratively.展开更多
Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
Formation control of multiple spacecraft has attracted extensive research attention.However,achieving reliable performance under sensor failures remains a significant challenge.This paper develops an integrated framew...Formation control of multiple spacecraft has attracted extensive research attention.However,achieving reliable performance under sensor failures remains a significant challenge.This paper develops an integrated framework that jointly designs distributed observers and local controllers to ensure robust formation control in the presence of external disturbances and sensor malfunctions.Treating the spacecraft formation as a single interconnected system,each spacecraft constructs a distributed observer that estimates the overall system state by incorporating both its own measurements and the predicted control information shared among the spacecraft.Based on the observer estimates,a local control law is synthesized to maintain the desired formation.Rigorous theoretical analysis and numerical simulations demonstrate that the proposed integrated approach effectively guarantees formation stability and resilience against sensor failures and disturbances.展开更多
Driven by the trend of device miniaturization and high-density integration,the interaction between adjacent electrodes has become a critical factor affecting the interfacial reliability of thermoelectric(TE)structures...Driven by the trend of device miniaturization and high-density integration,the interaction between adjacent electrodes has become a critical factor affecting the interfacial reliability of thermoelectric(TE)structures.This study investigates the influence of adjoining electrode interactions on the interfacial response of a multi-electrode/TE substrate structure,including interfacial stresses and stress intensity factors at the electrode ends.To solve the corresponding boundary-value problem,the Fourier transforms are adopted to derive a governing integro-differential equation for the interfacial shear stress in multi-electrode systems,incorporating the TE effects as generalized forces on the right-hand side.The results show that both the interfacial tension and transverse stress in the electrodes are significantly affected by the presence of adjacent electrodes.The interaction between neighboring electrodes diminishes as their spacing increases or when an adhesive interlayer is introduced.Furthermore,the softer and thinner electrodes,the softer and thicker adhesive interlayer,and the smaller TE loads are found to be beneficial for improving the interfacial performance.These findings may contribute to the accurate measurement in surface sensors and layout design of multi-point health monitoring systems for TE structures.展开更多
BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning ofte...BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.展开更多
AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patie...AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.展开更多
Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more ...Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more effective and safer treatments.In the present study,we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and evaluated its effects on pathogenic CD4^(+)T cell activation both in vivo and in vitro.Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis,as demonstrated by reduced demyelination and neuroinflammation.Moreover,Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression.Lycium barbarum glycopeptide also modulated pathogenic CD4^(+)T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion.Notably,no side effects were observed,suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide.Furthermore,RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1,an essential regulator of T cell activation and differentiation.This finding was supported by the reversal of T helper/T helper 17 cell response suppression upon AP-1 blockade.Collectively,these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4^(+)T cell-associated autoimmune or inflammatory diseases,such as multiple sclerosis.展开更多
针对多部位损伤(Multiple Site Damage,MSD)结构安全性评估问题,通过Monte-Carlo方法对MSD结构的失效概率进行预测和分析。首先,基于多孔铝板的多裂纹萌生试验,得出裂纹萌生寿命服从对数正态分布,为多裂纹萌生分析提供支持;通过多孔铝...针对多部位损伤(Multiple Site Damage,MSD)结构安全性评估问题,通过Monte-Carlo方法对MSD结构的失效概率进行预测和分析。首先,基于多孔铝板的多裂纹萌生试验,得出裂纹萌生寿命服从对数正态分布,为多裂纹萌生分析提供支持;通过多孔铝板的剩余强度试验得到铆钉孔直径、铆钉孔间距和裂纹萌生位置对结构剩余强度均有一定影响。其次,通过对裂纹萌生寿命分布进行随机抽样生成初始裂纹并使用组合法结合Paris公式,实现多裂纹随机扩展的模拟;在试验数据基础上,对传统的Irwin塑性区连通准则进行改进,发现改进的Irwin塑性区连通准则在孔间距大于10mm时的误差大大降低,并结合净截面屈服准则以获得更好的剩余强度预测结果;将随机性的裂纹萌生和扩展过程与确定性的剩余强度预测方法相结合,建立基于Monte-Carlo方法的MSD结构的失效概率预测模型。最后,通过算例分析,该模型能够得到MSD结构的失效概率曲线,实现结构安全性评估。结果表明MSD结构的失效概率会在短时间内迅速增加,需要在裂纹萌生寿命附近进行限制。展开更多
Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple pri...BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.展开更多
The multiple nuclides identification algorithm with low consumption and strong robustness is crucial for rapid radioactive source searching.This study investigates the design of a low-consumption multiple nuclides ide...The multiple nuclides identification algorithm with low consumption and strong robustness is crucial for rapid radioactive source searching.This study investigates the design of a low-consumption multiple nuclides identification algorithm for portable gamma spectrometers.First,the gamma spectra of 12 target nuclides(including the background case)were measured to create training datasets.The characteristic energies,obtained through energy calibration and full-energy peak addresses,are utilized as input features for a neural network.A large number of single-and multiple-nuclide training datasets are generated using random combinations and small-range drifting.Subsequently,a multi-label classification neural network based on a binary cross-entropy loss function is applied to export the existence probability of certain nuclides.The designed algorithm effectively reduces the computation time and storage space required by the neural network and has been successfully implemented in a portable gamma spectrometer with a running time of t_(r)<2 s.Results show that,in both validation and actual tests,the identification accuracy of the designed algorithm reaches 94.8%,for gamma spectra with a dose rate of d≈0.5μSv∕h and a measurement time t_(m)=60 s.This improves the ability to perform rapid on-site nuclide identification at important sites.展开更多
Steel slag(SS)accumulates unavoidably due to its complex and unstable composition,high production volumes,and limited value-added resource utilization.Single or multiple interface modifiers were proposed to enhance th...Steel slag(SS)accumulates unavoidably due to its complex and unstable composition,high production volumes,and limited value-added resource utilization.Single or multiple interface modifiers were proposed to enhance the properties of SS through high-speed dispersion,transforming its inherent hydrophilic and oleophobic characteristics into hydrophily and lipophilicity.The modification effects were innovatively assessed by observing the color changes of modified steel slag solutions following the dissolution-settlement equilibrium constant.This approach avoided human-induced errors and improved estimated accuracy in conformance with conventional methods such as oil absorption value,activation index,sedimentation volume,and lipophilicity.The hydrolysis of 3-aminopropyltriethoxysilane(KH)generated–Si(OH)_(3)structure to form hydrogen or covalent bonds with active substances(OH groups)from SS.Concurrently,SS underwent encapsulation via Si–O–Si structure resulting from the dehydration of–Si(OH)_(3).The stearic acid coupling agent(SA),aluminate coupling agent(AC),and titanate coupling agent(TN)underwent chemical reactions with Ca(OH)_(2),Al(OH)_(3),and CaCO_(3)in SS.The acidic SA primarily created stable chemical bonds and acted as a supplement due to its package,reducing surface activity and hydrophilicity while enhancing lipophilicity.Specifically,the optimal modification effect was obtained at 3 wt.%SA.Consequently,3 wt.%SA was established as the benchmark for multiple modifiers and the most effective combination was 3 wt.%SA and 3 wt.%AC.Compared with a single interface modifier,SA corroded the SS surface to provide numerous active sites for further modification by KH,AC,or TN,resulting in a more densely packed structure.In addition,more organic groups on SS prevent the proximity of other particles from agglomerating to achieve dispersion and a synergistic modification,laying a theoretical foundation of SS in a new pathway for organic composite materials.展开更多
Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-targe...Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.展开更多
This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to d...This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.展开更多
In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology bas...In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.展开更多
Multiple quantum well(MQW) Ⅲ-nitride diodes that can simultaneously emit and detect light feature an overlapping region between their electroluminescence and responsivity spectra, which allows them to be simultaneous...Multiple quantum well(MQW) Ⅲ-nitride diodes that can simultaneously emit and detect light feature an overlapping region between their electroluminescence and responsivity spectra, which allows them to be simultaneously used as both a transmitter and a receiver in a wireless light communication system. Here, we demonstrate a mobile light communication system using a time-division multiplexing(TDM) scheme to achieve bidirectional data transmission via the same optical channel.Two identical blue MQW diodes are defined by software as a transmitter or a receiver. To address the light alignment issue, an image identification module integrated with a gimbal stabilizer is used to automatically detect the locations of moving targets;thus, underwater audio communication is realized via a mobile blue-light TDM communication mode. This approach not only uses a single link but also integrates mobile nodes in a practical network.展开更多
Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
Objective:Multiple myeloma(MM)is a hematologically malignant clonal plasma cell disease.This study aims to explore the association between immunophenotypes and prognosis in patients with MM,to determine whether the ex...Objective:Multiple myeloma(MM)is a hematologically malignant clonal plasma cell disease.This study aims to explore the association between immunophenotypes and prognosis in patients with MM,to determine whether the expression of CD45 and CD200 is related to the prognosis of newly diagnosed MM(NDMM)patients,and to evaluate the significance of the combined expression of CD45 and CD200 in NDMM.Methods:A total of 123 NDMM patients admitted to Shengjing Hospital of China Medical University from July 2015 to August 2019 were enrolled.Five key immunophenotypic markers(including CD38,CD138,CD45,CD56,and CD200)were screened through flow cytometry and identified using random forest analysis and univariate Cox regression analysis.Patients were divided into 3 groups:Group A,CD45 and CD200 double-positive;Group B,CD45 or CD200 single-positive;Group C,CD45 and CD200 double-negative.Kaplan-Meier curves were used to analyze overall survival(OS)and progression-free survival(PFS)across groups.Multivariate Cox regression was performed to evaluate prognostic factors,and a nomogram was constructed based on these results.Results:The OS and PFS of single-positive groups for CD38,CD138,CD45,CD56,and CD200 were all shorter than those of their respective single-negative groups(all P<0.05).Significant differences were observed in OS(P<0.001)and PFS(P=0.001)among Groups A,B,and C.Group A had shorter OS and PFS(all P=0.001)compared to the Group B+C(cases from Group B and Group C were combined).CD45 and CD200 double-positive was an independent prognostic factor for NDMM[hazard ratio(HR)=2.178,95%confidence interval(CI)1.048 to 4.529;P=0.037].The nomogram and calibration curves constructed from multivariate Cox regression analysis demonstrated good concordance(concordance index=0.706;95%CI 0.661 to 0.751).Conclusion:NDMM patients with double-positive expression of CD45 and CD200 have significantly shorter OS and PFS.Compared with the use of either marker alone,the combined assessment of CD45 and CD200 may provide better prognostic stratification for MM patients.展开更多
基金Supported by the Shenzhen Key Laboratory of Control Theory and Intelligent Systems (ZDSYS20220330161800001)the National Natural Science Foundation of China (62303207)the Guangdong Basic and Applied Basic Research Foundation (2024A1515010725)。
文摘This paper studies cooperative robust parallel operation of multiple actuators over an undirected communication graph.The plant is modeled as an uncertain linear system,and the actuators are linear and identical.Based on the internal model principle,a distributed dynamic output feedback control law is proposed to achieve both robust output regulation of the closed-loop system and plant input sharing among the actuators.A practical example of five motors cooperatively driving an uncertain shaft under an external load torque is presented to show the effectiveness of the proposed control law.
基金supported in part by the International Science and Technology Project of Guangzhou Development District under Grant 2023GH08the Science and Technology Development Fund,MSAR,under Grants 0029/2022/AGJ and 0029/2023/RIA1the Program of Guangdong under Grant 2023A0505020003.
文摘To conduct marine surveys,multiple unmanned surface vessels(Multi-USV)with different capabilities perform collaborative mapping in multiple designated areas.This paper proposes a task allocation algorithm based on integer linear programming(ILP)with flow balance constraints,ensuring the fair and efficient distribution of sub-areas among USVs and maintaining strong connectivity of assigned regions.In the established gridmap,a search-based path planning algorithm is performed on the sub-areas according to the allocation scheme.It uses the greedy algorithm and the A*algorithm to achieve complete coverage of the barrier-free area and obtain an efficient trajectory of each USV.The greedy algorithm enables fast local traversal of unvisited grids,while the A*algorithm ensures navigation to escape from deadlock areas and maintains global path continuity.The comparison of task allocation results proves that the task allocation algorithm based on ILP improves the mapping efficiency and task distribution fairness.The proposed allocation method and result analysis provide a certain reference for the practical application ofMulti-USV to perform survey tasks collaboratively.
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
基金supported by the National Natural Science Foundation of China(62088101,62522307,62273045,U2341213)Beijing Nova Program(20230484481)。
文摘Formation control of multiple spacecraft has attracted extensive research attention.However,achieving reliable performance under sensor failures remains a significant challenge.This paper develops an integrated framework that jointly designs distributed observers and local controllers to ensure robust formation control in the presence of external disturbances and sensor malfunctions.Treating the spacecraft formation as a single interconnected system,each spacecraft constructs a distributed observer that estimates the overall system state by incorporating both its own measurements and the predicted control information shared among the spacecraft.Based on the observer estimates,a local control law is synthesized to maintain the desired formation.Rigorous theoretical analysis and numerical simulations demonstrate that the proposed integrated approach effectively guarantees formation stability and resilience against sensor failures and disturbances.
基金Project supported by the National Natural Science Foundation of China(Nos.12502117,12272269,11972257)the Natural Science Foundation of Ningxia of China(No.2024AAC03018)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Shanghai Gaofeng Project for University Academic Program Development。
文摘Driven by the trend of device miniaturization and high-density integration,the interaction between adjacent electrodes has become a critical factor affecting the interfacial reliability of thermoelectric(TE)structures.This study investigates the influence of adjoining electrode interactions on the interfacial response of a multi-electrode/TE substrate structure,including interfacial stresses and stress intensity factors at the electrode ends.To solve the corresponding boundary-value problem,the Fourier transforms are adopted to derive a governing integro-differential equation for the interfacial shear stress in multi-electrode systems,incorporating the TE effects as generalized forces on the right-hand side.The results show that both the interfacial tension and transverse stress in the electrodes are significantly affected by the presence of adjacent electrodes.The interaction between neighboring electrodes diminishes as their spacing increases or when an adhesive interlayer is introduced.Furthermore,the softer and thinner electrodes,the softer and thicker adhesive interlayer,and the smaller TE loads are found to be beneficial for improving the interfacial performance.These findings may contribute to the accurate measurement in surface sensors and layout design of multi-point health monitoring systems for TE structures.
基金Supported by Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2023MSXM060.
文摘BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.
文摘AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.
基金supported by the National Natural Science Foundational of China,Nos.U24A20692(to CJZ),82371355(to CJZ),and 82101414(to MH)National NaturalScience Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)+5 种基金Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovationand Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’sHospital,No.30420230005Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(toCJZ)Sichuan Science and Technology Support Project,No.2023YFS0212(to BH)Project of Sichuan Provincial Health Commission,No.19PJ265(to LD).
文摘Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more effective and safer treatments.In the present study,we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and evaluated its effects on pathogenic CD4^(+)T cell activation both in vivo and in vitro.Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis,as demonstrated by reduced demyelination and neuroinflammation.Moreover,Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression.Lycium barbarum glycopeptide also modulated pathogenic CD4^(+)T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion.Notably,no side effects were observed,suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide.Furthermore,RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1,an essential regulator of T cell activation and differentiation.This finding was supported by the reversal of T helper/T helper 17 cell response suppression upon AP-1 blockade.Collectively,these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4^(+)T cell-associated autoimmune or inflammatory diseases,such as multiple sclerosis.
文摘针对多部位损伤(Multiple Site Damage,MSD)结构安全性评估问题,通过Monte-Carlo方法对MSD结构的失效概率进行预测和分析。首先,基于多孔铝板的多裂纹萌生试验,得出裂纹萌生寿命服从对数正态分布,为多裂纹萌生分析提供支持;通过多孔铝板的剩余强度试验得到铆钉孔直径、铆钉孔间距和裂纹萌生位置对结构剩余强度均有一定影响。其次,通过对裂纹萌生寿命分布进行随机抽样生成初始裂纹并使用组合法结合Paris公式,实现多裂纹随机扩展的模拟;在试验数据基础上,对传统的Irwin塑性区连通准则进行改进,发现改进的Irwin塑性区连通准则在孔间距大于10mm时的误差大大降低,并结合净截面屈服准则以获得更好的剩余强度预测结果;将随机性的裂纹萌生和扩展过程与确定性的剩余强度预测方法相结合,建立基于Monte-Carlo方法的MSD结构的失效概率预测模型。最后,通过算例分析,该模型能够得到MSD结构的失效概率曲线,实现结构安全性评估。结果表明MSD结构的失效概率会在短时间内迅速增加,需要在裂纹萌生寿命附近进行限制。
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
基金Supported by Gansu Provincial Natural Science Foundation,No.21JR1RA010In-Hospital Research Fund of Gansu Provincial Hospital,No.23GSSYD-5.
文摘BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.
文摘The multiple nuclides identification algorithm with low consumption and strong robustness is crucial for rapid radioactive source searching.This study investigates the design of a low-consumption multiple nuclides identification algorithm for portable gamma spectrometers.First,the gamma spectra of 12 target nuclides(including the background case)were measured to create training datasets.The characteristic energies,obtained through energy calibration and full-energy peak addresses,are utilized as input features for a neural network.A large number of single-and multiple-nuclide training datasets are generated using random combinations and small-range drifting.Subsequently,a multi-label classification neural network based on a binary cross-entropy loss function is applied to export the existence probability of certain nuclides.The designed algorithm effectively reduces the computation time and storage space required by the neural network and has been successfully implemented in a portable gamma spectrometer with a running time of t_(r)<2 s.Results show that,in both validation and actual tests,the identification accuracy of the designed algorithm reaches 94.8%,for gamma spectra with a dose rate of d≈0.5μSv∕h and a measurement time t_(m)=60 s.This improves the ability to perform rapid on-site nuclide identification at important sites.
基金supported by the National Natural Science Foundation of China(U23A20605)Anhui Graduate Innovation and Entrepreneurship Practice Project(2022cxcysj090)+2 种基金China Baowu Low Carbon Metallurgy Innovation Foundation(BWLCF202202)the University Synergy Innovation Program of Anhui Province(GXXT-2020-072)the Outstanding Youth Fund of Anhui Province(2208085J19).
文摘Steel slag(SS)accumulates unavoidably due to its complex and unstable composition,high production volumes,and limited value-added resource utilization.Single or multiple interface modifiers were proposed to enhance the properties of SS through high-speed dispersion,transforming its inherent hydrophilic and oleophobic characteristics into hydrophily and lipophilicity.The modification effects were innovatively assessed by observing the color changes of modified steel slag solutions following the dissolution-settlement equilibrium constant.This approach avoided human-induced errors and improved estimated accuracy in conformance with conventional methods such as oil absorption value,activation index,sedimentation volume,and lipophilicity.The hydrolysis of 3-aminopropyltriethoxysilane(KH)generated–Si(OH)_(3)structure to form hydrogen or covalent bonds with active substances(OH groups)from SS.Concurrently,SS underwent encapsulation via Si–O–Si structure resulting from the dehydration of–Si(OH)_(3).The stearic acid coupling agent(SA),aluminate coupling agent(AC),and titanate coupling agent(TN)underwent chemical reactions with Ca(OH)_(2),Al(OH)_(3),and CaCO_(3)in SS.The acidic SA primarily created stable chemical bonds and acted as a supplement due to its package,reducing surface activity and hydrophilicity while enhancing lipophilicity.Specifically,the optimal modification effect was obtained at 3 wt.%SA.Consequently,3 wt.%SA was established as the benchmark for multiple modifiers and the most effective combination was 3 wt.%SA and 3 wt.%AC.Compared with a single interface modifier,SA corroded the SS surface to provide numerous active sites for further modification by KH,AC,or TN,resulting in a more densely packed structure.In addition,more organic groups on SS prevent the proximity of other particles from agglomerating to achieve dispersion and a synergistic modification,laying a theoretical foundation of SS in a new pathway for organic composite materials.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271292,31872723,32200778,and 22377089)the Jiangsu Students Innovation and Entrepre-neurship Training Program,China(Program No.:202210285081Z)+6 种基金the Project of MOE Key Laboratory of Geriatric Diseases and Immunology,China(Project No.:JYN202404)Proj-ect Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province,China(Project No.:BK20220494)Suzhou Medical and Health Technology Innovation Project,China(Grant No.:SKY2022107)the Clinical Research Center of Neuro-logical Disease in The Second Affiliated Hospital of Soochow University,China(Grant No.:ND2022A04)State Key Laboratory of Drug Research(Grant No.:SKLDR-2023-KF-05)Jiangsu Shuang-chuang Program for Doctor,Young Science Talents Promotion Project of Jiangsu Science and Technology Association(Program No.:TJ-2023-019)Young Science Talents Promotion Project of Suzhou Science and Technology Association,Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and startup funding(Grant Nos.:NH21500221,NH21500122,and NH21500123)to Qifei Cong.
文摘Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
基金supported by DST-FIST(Government of India)(Grant No.SR/FIST/MS-1/2017/13)and Seed Money Project(Grant No.DoRDC/733).
文摘This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.
基金financially supported by National Key R&D Program(2021YFF0701905)。
文摘In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.
基金jointly supported by the National Natural Science Foundation of China (U21A20495)Natural Science Foundation of Jiangsu Province (BG2024023)+1 种基金National Key Research and Development Program of China (2022YFE0112000)111 Project (D17018)。
文摘Multiple quantum well(MQW) Ⅲ-nitride diodes that can simultaneously emit and detect light feature an overlapping region between their electroluminescence and responsivity spectra, which allows them to be simultaneously used as both a transmitter and a receiver in a wireless light communication system. Here, we demonstrate a mobile light communication system using a time-division multiplexing(TDM) scheme to achieve bidirectional data transmission via the same optical channel.Two identical blue MQW diodes are defined by software as a transmitter or a receiver. To address the light alignment issue, an image identification module integrated with a gimbal stabilizer is used to automatically detect the locations of moving targets;thus, underwater audio communication is realized via a mobile blue-light TDM communication mode. This approach not only uses a single link but also integrates mobile nodes in a practical network.
基金supported by the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.
基金supported by the National Natural Science Foundation,China(81870166).
文摘Objective:Multiple myeloma(MM)is a hematologically malignant clonal plasma cell disease.This study aims to explore the association between immunophenotypes and prognosis in patients with MM,to determine whether the expression of CD45 and CD200 is related to the prognosis of newly diagnosed MM(NDMM)patients,and to evaluate the significance of the combined expression of CD45 and CD200 in NDMM.Methods:A total of 123 NDMM patients admitted to Shengjing Hospital of China Medical University from July 2015 to August 2019 were enrolled.Five key immunophenotypic markers(including CD38,CD138,CD45,CD56,and CD200)were screened through flow cytometry and identified using random forest analysis and univariate Cox regression analysis.Patients were divided into 3 groups:Group A,CD45 and CD200 double-positive;Group B,CD45 or CD200 single-positive;Group C,CD45 and CD200 double-negative.Kaplan-Meier curves were used to analyze overall survival(OS)and progression-free survival(PFS)across groups.Multivariate Cox regression was performed to evaluate prognostic factors,and a nomogram was constructed based on these results.Results:The OS and PFS of single-positive groups for CD38,CD138,CD45,CD56,and CD200 were all shorter than those of their respective single-negative groups(all P<0.05).Significant differences were observed in OS(P<0.001)and PFS(P=0.001)among Groups A,B,and C.Group A had shorter OS and PFS(all P=0.001)compared to the Group B+C(cases from Group B and Group C were combined).CD45 and CD200 double-positive was an independent prognostic factor for NDMM[hazard ratio(HR)=2.178,95%confidence interval(CI)1.048 to 4.529;P=0.037].The nomogram and calibration curves constructed from multivariate Cox regression analysis demonstrated good concordance(concordance index=0.706;95%CI 0.661 to 0.751).Conclusion:NDMM patients with double-positive expression of CD45 and CD200 have significantly shorter OS and PFS.Compared with the use of either marker alone,the combined assessment of CD45 and CD200 may provide better prognostic stratification for MM patients.
