Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate;however,the molecular mechanisms underpinning its pathogenesis are not well elucidated.Here,a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus(SGIV),focusing on the roles of key metabolites.Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver.Furthermore,SGIV significantly reduced the contents of lipid droplets,triglycerides,cholesterol,and lipoproteins.Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways,with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid(ALA),consistent with disturbed lipid homeostasis in the liver.Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide,carbohydrate,amino acid,and lipid metabolism,supporting the conclusion that SGIV infection induced liver metabolic reprogramming.Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade.Of note,integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid(LA)metabolites,and the accumulation of L-glutamic acid(GA),accompanied by alterations in immune,inflammation,and cell death-related genes.Further experimental data showed that ALA,but not GA,suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host.Collectively,these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.

Regional Multi-Agent Cooperative Reinforcement Learning for City-Level Traffic Grid Signal Control

This article studies the effective traffic signal control problem of multiple intersections in a city-level traffic system.A novel regional multi-agent cooperative reinforcement learning algorithm called RegionSTLight is proposed to improve the traffic efficiency.Firstly a regional multi-agent Q-learning framework is proposed,which can equivalently decompose the global Q value of the traffic system into the local values of several regions Based on the framework and the idea of human-machine cooperation,a dynamic zoning method is designed to divide the traffic network into several strong-coupled regions according to realtime traffic flow densities.In order to achieve better cooperation inside each region,a lightweight spatio-temporal fusion feature extraction network is designed.The experiments in synthetic real-world and city-level scenarios show that the proposed RegionS TLight converges more quickly,is more stable,and obtains better asymptotic performance compared to state-of-theart models.

Reversible Mn^(2+)/Mn^(4+)double-electron redox in P3-type layer-structured sodium-ion cathode

The balance between cationic redox and oxygen redox in layer-structured cathode materials is an important issue for sodium batteries to obtain high energy density and considerable cycle stability.Oxygen redox can contribute extra capacity to increase energy density,but results in lattice instability and capacity fading caused by lattice oxygen gliding and oxygen release.In this work,reversible Mn^(2+)/Mn^(4+)redox is realized in a P3-Na_(0.65)Li_(0.2)Co_(0.05)Mn_(0.75)O_(2)cathode material with high specific capacity and structure stability via Co substitution.The contribution of oxygen redox is suppressed significantly by reversible Mn^(2+)/Mn^(4+)redox without sacrificing capacity,thus reducing lattice oxygen release and improving the structure stability.Synchrotron X-ray techniques reveal that P3 phase is well maintained in a wide voltage window of 1.5-4.5 V vs.Na^(+)/Na even at 10 C and after long-term cycling.It is disclosed that charge compensation from Co/Mn-ions contributes to the voltage region below 4.2 V and O-ions contribute to the whole voltage range.The synergistic contributions of Mn^(2+)/Mn^(4+),Co^(2+)/Co^(3+),and O^(2-)/(O_n)^(2-)redox in P3-Na_(0.65)Li_(0.2)Co_(0.05)Mn_(0.75)O_(2)lead to a high reversible capacity of 215.0 m A h g^(-1)at 0.1 C with considerable cycle stability.The strategy opens up new opportunities for the design of high capacity cathode materials for rechargeable batteries.

重组弹性蛋白的表征及在紫外诱导皮肤光老化过程中的作用

采用基因工程技术构建重组弹性蛋白工程菌,再利用发酵纯化技术得到重组弹性蛋白,并经氨基酸N端测序、分子量测定、氨基酸组成、蛋白纯度分析、内毒素含量测定及其红外光谱和圆二色谱分析对其进行表征鉴定。通过测定重组弹性蛋白对L929小鼠胚胎成纤维细胞粘附能力和细胞活力影响,以及在中波紫外线(UVB)诱导L929细胞光老化模型中,考察重组弹性蛋白对Ⅰ型胶原蛋白(CollagenⅠ)、Ⅲ型胶原蛋白(CollagenⅢ)、弹性蛋白(Elastin)以及基质金属蛋白酶1(MMP-1)mRNA转录水平的影响,探究重组弹性蛋白在UVB诱导皮肤光老化过程中的作用。结果表明,获得的重组弹性蛋白与天然弹性蛋白二级结构相似;在0.1 mg/mL质量浓度下无细胞毒性且具有一定的细胞活力,显著促进L929细胞的粘附和增殖。此外,重组弹性蛋白可通过下调UVB辐射后L929细胞内MMP-1转录水平,提高细胞中的CollagenⅠ,CollagenⅢ和Elastin表达,对UVB诱导的L929细胞光损伤具有良好的保护作用,显著提升L929细胞的存活率。

The Value of MLPR,NLR,and RDW in the Assessment of Combined Pulmonary Embolism in Elderly Patients with AECOPD

Objective:To investigate the diagnostic value of the monocyte-to-large-platelet ratio(MLPR),neutrophil-to-lymphocyte ratio(NLR),and red blood cell distribution width(RDW)for pulmonary embolism(PE)in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods:A total of 60 elderly AECOPD patients were enrolled and divided into embolus group(12 cases)and thrombus group(48 cases)according to whether they were combined with pulmonary embolism and the MLPR,NLR,and RDW values of the two groups were determined respectively.Results:The patients in the two groups had different degrees of vascular structural and functional abnormalities,and the MLPR,NLR,and RDW in the embolus group were significantly higher than those in the thrombus group(P<0.05);while the differences in NLR and RDW between the two groups were not significant.Conclusion:MLPR,NLR,and RDW can provide an objective basis for assessing PE in elderly AECOPD patients.

Yinqiao Sanhuang Paste Combined with Traditional Chinese Medicine Plaster for the Intervention of Drug Rash Induced by Targeted Therapy in Lung Cancer

Objective:To observe the efficacy and safety of Yinqiao Sanhuang Paste combined with traditional Chinese medicine plaster in treating drug rash caused by targeted therapy in lung cancer.Methods:A total of 100 lung cancer patients treated at our hospital from January 2021 to December 2023 were selected and randomly divided into an observation group and a control group,with 50 patients in each group.The control group received conventional medication,while the observation group was treated with Yinqiao Sanhuang Paste combined with traditional Chinese medicine plaster.The clinical symptom improvement and adverse reactions in both groups were observed.Results:The effective rate in the control group was 80.00%,while in the observation group,it was 96.00%,with a statistically significant difference between the two groups(P<0.05).The onset time,duration,and significant effect time in the control group were(2.41±0.29)days,(4.42±1.21)days,and(5.45±0.29)days,respectively;in the observation group,they were(2.44±0.21)days,(4.28±1.11)days,and(5.57±1.01)days,respectively.There was no statistically significant difference in the total onset time and total duration between the two groups(P>0.05).The incidence of adverse reactions in the control group was 28.00%,higher than the observation group’s 10.00%(P<0.05).Conclusion:Yinqiao Sanhuang Paste combined with traditional Chinese medicine plaster can effectively reduce the symptoms of drug rash induced by targeted therapy in lung cancer and lower the incidence of adverse reactions,indicating good clinical application value.

Current treatment paradigm and survival outcomes among patients with newly diagnosed multiple myeloma in China:a retrospective multicenter study

Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).

Data analysis guidelines for single‑cell RNA‑seq in biomedical studies and clinical applications

The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies.With the expansion of capacity for high-throughput scRNA-seq,including clinical samples,the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field.Here,we review the workflow for typical scRNA-seq data analysis,covering raw data processing and quality control,basic data analysis applicable for almost all scRNA-seq data sets,and advanced data analysis that should be tailored to specific scientific questions.While summarizing the current methods for each analysis step,we also provide an online repository of software and wrapped-up scripts to support the implementation.Recommendations and caveats are pointed out for some specific analysis tasks and approaches.We hope this resource will be helpful to researchers engaging with scRNA-seq,in particular for emerging clinical applications.

Heavy metals potentially drive co-selection of antibiotic resistance genes by shifting soil bacterial communities in paddy soils along the middle and lower Yangtze River

Heavy metals(HMs)and antibiotic resistance have become serious environmental problems affecting soil and human health.Soil microorganisms play key roles in pollutant degradation and biogeochemical cycling processes;however,the interactions among HMs,soil microbial communities,and antibiotic resistance genes(ARGs)in agricultural soils remain unclear.Using quantitative real-time polymerase chain reaction and NovaSeq sequencing,we evaluated heavy metal contents,abundances of ARGs,soil bacterial community structure and functions,and their correlations in paddy soils at 43 sampling sites along the middle and lower reaches of the Yangtze River,central and eastern China.Our results showed the co-occurrence of HMs,ARGs,and HM resistance genes across all paddy soils.Additionally,significant positive associations were detected between HMs and resistance genes.Cadmium,czcA,and int1 were positively correlated with bacterial community diversity.The Mantel test showed that bacterial community composition and functions were significantly associated with HMs and resistance genes,such as Cd,Cr,Zn,copA,czcA,int1,and sul1.Moreover,HMs and ARGs were the major factors shaping soil bacterial communities;thus,HMs triggered proliferation of HM and antibiotic resistances by influencing the mobile genetic element(int1)and soil microbial communities.Our study revealed that HMs potentially drive the co-selection of ARGs by shifting soil bacterial community structure and functions,thereby increasing the potential risks to human health as well as ecological environment in the paddy soils along the middle and lower reaches of the Yangtze River.

叶片裂纹故障早期监测预警方法研究

振动问题一直是限制风机向大型化高参数化方向发展的主要障碍,而叶片振动导致的疲劳断裂故障和事故尤为突出。对风机叶片同步共振进行了研究,提出基于非线性最小二乘拟合和GARIV方法相结合的叶片同步振动的振动参数精确辨识方法,准确捕捉叶片的动态固有频率。基于激光传感器的叶尖定时方法,通过捕捉叶片裂纹早期固有频率的微小变化,实现叶片裂纹故障的早期预警。仿真结果表明,所提出的方法可以达到万分之七的测量精度,实验研究结果表明,本文所提出的方法可以进行叶片裂纹的早期识别。

高速公路改扩建中乳化沥青冷再生混合料设计方法优化研究

结合某高速改扩建工程乳化沥青冷再生试验段,分别对乳化沥青厂拌冷再生混合料采用旋转压实成型方法和大马歇尔成型方法进行混合料的设计,对两种成型方法的混合料最佳含水率、混合料的体积指标、混合料的性能进行分析。实验结果表明,两种设计方法的混合料技术指标存在一定的差异,项目采用旋转压实70次和采用大马歇尔双面击实150次的混合料体积指标和性能指标相近,通过与试验路取芯状况的对比,确定本项目采用马歇尔双面击实150次和旋转压实70次作为本项目的混合料成型方法。

通过聚丙烯/聚乙烯二元体系的流变控制制备聚合物多层片材

通过毛细管流变仪研究了二元聚合物体系的分相流动行为,以及在动态外场作用下的演变规律,利用低黏度熔体包覆高黏度熔体的"粘性包覆"现象,筛选出具有满足分相流动条件并特定黏度比的聚乙烯(PE)和聚丙烯(PP),成功地一次成型制备出多层聚合物膜片。利用凝胶色谱仪、偏光显微镜、有限元分析软件等对PP/PE二元体系的形态结构进行了研究,并探讨了分层流动的机理。结果表明,通过PE/PP黏度比可以控制材料流变行为,从而制备"核壳"结构和PP-PE-PP"三明治"结构,并优化出最适宜的加工窗口。同时,发现流动过程中PP和PE的径向速度是不同的,分层流动是材料粘弹性和加工流场共同作用的结果。

Circular Formation Flight Control for Unmanned Aerial Vehicles With Directed Network and External Disturbance

This paper proposes a new distributed formation flight protocol for unmanned aerial vehicles(UAVs)to perform coordinated circular tracking around a set of circles on a target sphere.Different from the previous results limited in bidirectional networks and disturbance-free motions,this paper handles the circular formation flight control problem with both directed network and spatiotemporal disturbance with the knowledge of its upper bound.Distinguishing from the design of a common Lyapunov fiunction for bidirectional cases,we separately design the control for the circular tracking subsystem and the formation keeping subsystem with the circular tracking error as input.Then the whole control system is regarded as a cascade connection of these two subsystems,which is proved to be stable by input-tostate stability(ISS)theory.For the purpose of encountering the external disturbance,the backstepping technology is introduced to design the control inputs of each UAV pointing to North and Down along the special sphere(say,the circular tracking control algorithm)with the help of the switching function.Meanwhile,the distributed linear consensus protocol integrated with anther switching anti-interference item is developed to construct the control input of each UAV pointing to east along the special sphere(say,the formation keeping control law)for formation keeping.The validity of the proposed control law is proved both in the rigorous theory and through numerical simulations.

Constructing a multifunctional mesoporous composite of metallic cobalt nanoparticles and nitrogen-doped reduced graphene oxides for high-performance lithium-sulfur batteries

Electrochemical properties of lithium-sulfur(Li-S)batteries are mainly hindered by both the insulating nature of elemental sulfur(i.e.,molecular S8)and the shuttling effect or sluggish redox kinetics of lithium polysulfide intermediates(Li_(2)S_(n),3≤n≤8).In this paper,a three-dimensional mesoporous reduced graphene oxide-based nanocomposite,with the embedding of metallic Co nanoparticles and the doping of elemental N(Co/NrGO),and its simply ground mixture with powdered S at a mass ratio of 1:6(Co/NrGO/S)are prepared and used as cathode-/separator-coated interlayers and working electrodes in assembled Li-S cells,respectively.One of the effective cell configurations is to paste composite Co/NrGO onto both the S-loading cathode and separator,showing good cycling stability(1070mAh g^(−1) in the 100th cycle at 0.2 C),highrate capability(835mAh g^(−1),2.0 C),and excellent durability(905mAh g^(−1) in the 250th cycle at 0.5 or 0.2 C).Compared with the experimental results of Co-absent NrGO,electrochemical properties of various Co/NrGO-based cell configurations clearly show multiple functions of Co/NrGO,indicating that the absence of Co/NrGO coatings and/or Co nanoparticles may be inadequate to achieve superior S availability of assembled Li-S batteries.

Development and validation of a nomogram for predicting the risk of pressure injury in adult patients undergoing abdominal surgery

Objectives:This study aimed to develop a nomogram for predicting the risk of pressure injury(PI)in adult patients undergoing abdominal surgery and validate its effectiveness among these patients.Methods:This study retrospectively included 11,247 adult patients,who underwent abdominal surgery and postoperative supervision in ICU,in a tertiary care hospital in western China between January 2017 and December 2020.All datasets were extracted from the patient’s medical records and randomly divided into the training cohort(8,997)and the validation cohort(2,250)by 8:2.The univariable logistic regression was used to select potentially relevant features.Then,multivariable logistic regression was also conducted and utilized to establish the nomogram.The nomogram was compared with the Braden scale for predicting PI in the validation cohort through the area under the curve(AUC)of the receiver operator characteristic(ROC)curve,Hosmer-Lemeshow(H-L)test,and decision curve analysis(DCA).Results:873(7.8%)patients suffered PIs.Logistic regression analysis showed that time of operation,weight,type of operation,albumin,and Braden scale score were independent risk factors for PI.A nomogram integrating five selected characteristics was constructed.The AUC of the ROC curve for the nomogram was 0.831,with a specificity of 85.2%and sensitivity of 63.7%.The AUC of the ROC curve for the Braden scale was 0.567,with a specificity of only 33.0%.The P-values of the H-L test were 0.45(nomogram)and 0.22(Braden scale),both indicating good calibration.The DCA also displayed that the nomogram had better predictive validity.Conclusion:Compared with the Braden scale,the nomogram showed a better predictive performance.This nomogram is informative and has the potential to better guide caregivers for risk stratification and prevention of PI,although it requires further validation.

Stochastic DoS Attack Allocation Against Collaborative Estimation in Sensor Networks

In this paper,denial of service(DoS)attack management for destroying the collaborative estimation in sensor networks and minimizing attack energy from the attacker perspective is studied.In the communication channels between sensors and a remote estimator,the attacker chooses some channels to randomly jam DoS attacks to make their packets randomly dropped.A stochastic power allocation approach composed of three steps is proposed.Firstly,the minimum number of channels and the channel set to be attacked are given.Secondly,a necessary condition and a sufficient condition on the packet loss probabilities of the channels in the attack set are provided for general and special systems,respectively.Finally,by converting the original coupling nonlinear programming problem to a linear programming problem,a method of searching attack probabilities and power to minimize the attack energy is proposed.The effectiveness of the proposed scheme is verified by simulation examples.

基于瞬态启车数据的透平机械叶片健康监测方法

叶片的振动及其导致的疲劳断裂问题一直是限制透平机械向大型高参数化方向发展的主要障碍,对叶片裂纹进行及时诊断预警是防止事故的重要手段。本文研究通过启停车数据进行叶片裂纹故障诊断的方法,提出基于非线性最小二乘拟合和AR方法相结合的基于叶片同步振动的叶片状态参数精确辨识方法,准确捕捉叶片的固有频率,通过固有频率的变化辨别叶片裂纹故障并进行早期预警。开展了仿真和实验研究,结果表明,共振中心在4 800r/min左右,升速速率30r/min/s时,本文所提出的方法可以达到万分之二的测量精度。搭建了叶片振动测量与故障预警试验台,实验研究结果表明,本文所提出的方法可以进行叶片的动频的精确识别。

Distribution and degradation kinetics of cyhalodiamide in Chinese rice field environment

Cyhalodiamide is a novel agrochemical which is effective against Lepidoptera pests,including Cnaphalocrocis medinalis,Chilo suppressalis,Pieris rapae,Plutella xylostella,Helicoverpa armigera,etc.In the study,a fast and accurate analytical method was developed to detect cyhalodiamide in Chinese typical rice field environment by a modified Qu ECh ERS(Quick,Easy,Cheap,Effective,Rugged,Safe)method with UPLC-MS/MS(ultra-high performance chromatography-tandem mass spectrometry).The mean recoveries of cyhalodiamide varied from 73.5% to 107.5%,with the RSDs from 1.2% to 10.7%.The limits of determination(LODs)were 0.0005 mg·kg^(-1),and the limits of quantitation(LOQs)were from 0.002 to 0.01 mg·kg^(-1)in all five matrices.This method was used to determine cyhalodiamide residues for studies of the distribution and degradation kinetics in rice field environment.The field trials results showed that cyhalodiamide was easily degradable and the half-lives were4.2–13.6 d in rice straw,8.77 d in paddy soil and 5.37–8.45 d in paddy water,respectively.The final residues of cyhalodiamide in brown rice were below 0.35 mg·kg^(-1).The used dosage of 33.75 g·hm^(-2)with pre-harvest interval(PHI)of 21 d and the maximum residue limit(MRL)of cyhalodiamide in rice at 0.1 mg·kg^(-1)were recommended,which would be safe to human health and environment.The developed analytical method will be useful to monitor cyhalodiamide residues and safety evaluation in rice environment.

Isolated coagulopathy without classic CRAB symptoms as the initial manifestation of multiple myeloma: A case report

BACKGROUND Multiple myeloma patients usually present with CRAB symptoms(hypercalcemia,renal disease,anemia and bone diseases)as initial manifestations.Bleeding symptoms are less common,most of which result from thrombocytopenia or infiltration of plasmacytoma.Relatively,coagulopathy is not so common,especially isolated coagulopathy without CRAB manifestations,which is very rare.Herein,we report a 54-year old female who was hospitalized for intermittent and recurrent mild oral mucosal hemorrhage without other bleeding symptoms for almost one month or typical myeloma features.CASE SUMMARY Two months before admission,the patient underwent implantation of a permanent pacemaker due to sick sinus syndrome.Prothrombin time and activated partial thromboplastin time were significantly prolonged.Factor X deficiency was demonstrated to account for the coagulation dysfunction.An M protein peak was shown by serum protein electrophoresis.26.11%of abnormal plasma cells were detected in bone marrow by flow cytometry,expressing CD38,CD138,CD56 and intracellular immunoglobulin Kappa light chain.Bone marrow biopsy also proved the presence of abnormal plasma cells,but Congo red stain was negative.The patient was finally diagnosed with multiple myeloma IgA-κtype.A literature review indicated that factor X deficiency was highly related to amyloidosis.Before bleeding signs,the patient had cardiac arrhythmia,enlargement of the heart,and progressive heart failure;thus,cardiac amyloidosis was suspected.CONCLUSION Bleeding related to coagulation dysfunction is uncommon in multiple myeloma,especially as the initial manifestation.Amyloidosis is a well-recognized cause of isolated acquired factor X deficiency.

Fetuin-A is an immunomodulator and a potential therapeutic option in BMP4-dependent heterotopic ossification and associated bone mass loss

Heterotopic ossification(HO)is the abnormal formation of bone in extraskeletal sites.However,the mechanisms linking HO pathogenesis with bone mass dysfunction remain unclear.Here,we showed that mice harboring injury-induced and BMP4-dependent HO exhibit bone mass loss similar to that presented by patients with HO.Moreover,we found that injury-induced hyperinflammatory responses at the injury site triggered HO initiation but did not result in bone mass loss at 1 day post-injury(dpi).In contrast,a suppressive immune response promoted HO propagation and bone mass loss by 7 dpi.Correcting immune dysregulation by PD1/PDL1 blockade dramatically alleviated HO propagation and bone mass loss.We further demonstrated that fetuin-A(FetA),which has been frequently detected in HO lesions but rarely observed in HO-adjacent normal bone,acts as an immunomodulator to promote PD1 expression and M2 macrophage polarization,leading to immunosuppression.Intervention with recombinant FetA inhibited hyperinflammation and prevented HO and associated bone mass loss.Collectively,our findings provide new insights into the osteoimmunological interactions that occur during HO formation and suggest that FetA is an immunosuppressor and a potential therapeutic option for the treatment of HO.