Evaluation of G3BP1 in the prognosis of acute and acute-on-chronic liver failure after the treatment of artificial liver support system

BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.

基于Kisspeptin/GPR54系统探讨新加二甲地黄汤对PCOS模型大鼠卵泡发育的影响

目的探讨经新加二甲地黄汤干预后的多囊卵巢综合征(polycystic ovary syndrome,PCOS)模型大鼠的卵泡发育情况及其可能存在的效应机制。方法筛选28只拥有规律动情周期的雌性SD大鼠,随机分为正常对照组、模型组、中药组及西药组,每组7只。除正常对照组外,其余三组均连续予来曲唑-羧甲基纤维素混悬液0.1mg/(kg·d)灌胃,以构建PCOS大鼠模型。自第22天起,中药组以新加二甲地黄汤5.268g/(kg·d)灌胃,西药组以炔雌醇环丙孕酮片0.286mg/(kg·d)灌胃,正常对照组及模型组均以10ml/(kg·d)蒸馏水灌胃。3周后比较各组大鼠卵巢系数,苏木精-伊红染色观察各组大鼠卵巢组织形态学改变,对各组大鼠血清激素均采用酶联免疫吸附试验进行检测,蛋白质印迹法检测卵巢亲吻素(kisspeptin,Kp)、G蛋白偶联受体54(G-protein-coupled receptor 54,GPR54)蛋白表达水平。结果与正常对照组比较,模型组大鼠卵巢内呈现为囊状扩张和闭锁的卵泡增多,其颗粒细胞层数变少,卵巢系数增大;血清睾酮(testosterone,T)、黄体生成素(luteinizing hormone,LH)、Kp水平升高;血清卵泡刺激素(follicle stimulating hormone,FSH)、雌二醇(estradiol,E2)水平及大鼠卵巢组织中Kp、GPR54蛋白表达均显著降低(P<0.05)。予中药干预后,与模型组比较,中药组大鼠卵巢囊样扩张卵泡数量变少,颗粒细胞的层数增多,存在近成熟的卵泡,并见少量黄体存在;大鼠血清LH、T、Kp水平下降,血清FSH、E2水平及卵巢Kp、GPR54蛋白表达显著升高(P<0.05)。结论PCOS模型大鼠的卵泡发育情况经新加二甲地黄汤干预后得以改善,该治疗机制可能为通过调控Kisspeptin/GPR54系统影响FSH和LH的释放,以此影响激素含量,调整卵巢功能,使卵泡发育和排卵能力得以改善。

基于N和G蛋白的HeV抗体间接ELISA检测方法的建立

为了建立亨德拉病毒(HeV)抗体的间接ELISA检测方法,人工合成HeV的N和G基因,并将其分别连接到原核表达载体PET-30a,经IPTG诱导、变复性处理及纯化后获得表达蛋白,免疫健康马获得阳性血清,用矩阵法对蛋白包被浓度和一抗稀释倍数进行确定,优化包被时间、封闭剂以及孵育时间等技术参数,并对建立方法的灵敏性、特异性、重复性和准确性进行评估。经SDS-PAGE和Western blot验证,N和G两个蛋白均实现高效表达,间接ELISA方法中二者的最佳包被浓度分别为10μg/mL和8μg/mL,一抗血清的稀释倍数为1∶800,优化后的最佳反应条件为:N蛋白4℃包被过夜,5%脱脂奶粉37℃封闭2 h,一抗孵育时间30 min,二抗按1∶8000稀释后37℃作用60 min;G蛋白4℃包被过夜,2%BSA 37℃封闭2 h,一抗孵育时间80 min,二抗按1∶8000稀释后37℃作用80 min。结果表明,所建方法N蛋白的灵敏性大于1∶12800,G蛋白大于1∶6400,二者的临界值分别为0.235和0.267,特异性良好,批内、批间变异系数均小于10%,重复性良好,二者ROC曲线下面积分别为0.91和0.93,准确性高。试验结果可为海关、口岸以及出入境检验检疫等部门HeV临床血清学诊断提供技术支撑。

NoV GⅡ.2亚型RT-RPA-CRISPR/Cas12a检测方法的建立

近年来,一种新的诺如病毒GⅡ.2亚型(norovirus GⅡ.2,NoV GⅡ.2)通过牡蛎等生食海鲜感染人群,引发急性胃肠炎,并在全球广泛传播。为实现NoV感染的现场诊断和快速疫情响应,亟需建立快速便捷的NoV GⅡ.2亚型核酸检测方法。本研究通过设计引物、crRNA,经优化反应条件后,建立了NoV GⅡ.2亚型RTRPA-CRISPR/Cas12a检测方法。结果显示:利用引物NoV-GⅡ.2-F1B和NoV-GⅡ.2-R1对NoV GⅡ.2标准RNA进行RT-RPA扩增,结合crRNA1介导的CRISPR/Cas12a报告体系,能在40 min内完成NoV GⅡ.2核酸检测;该方法检测灵敏度为10 copies/μL,且与轮状病毒、腺病毒、星形病毒、人副肠孤病毒、博卡病毒和札如病毒无交叉反应;应用该方法和qRT-PCR法,分别对30份临床模拟样本进行检测,发现总符合率达96.67%。结果表明,本研究建立的NoV GⅡ.2亚型RT-RPA-CRISPR/Cas12a检测方法无需依赖昂贵设备,具有灵敏度高、特异性强、操作便捷快速等特点,为NoV GⅡ.2感染的现场检测和防控提供了新方法。

面向6G的RIS辅助通信系统的信道估计技术

随着对未来6G技术的持续探索,RIS作为潜在的革命性技术之一,已展现出在提高通信系统容量、扩大覆盖范围和降低能耗等多个方面的巨大潜力。在RIS辅助的通信系统中,信道估计是实现RIS技术优势的关键环节之一。首先系统地概述了RIS的技术特点和在现代通信中的应用前景。然后,针对不同应用场景的特点,梳理并归纳了现有的RIS辅助通信场景中的信道估计关键技术,阐明了各研究热点的目标和方法。最后,探讨了RIS辅助通信场景中的信道估计技术在实际应用中所面临的技术挑战。

Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection

Porcine reproductive and respiratory syndrome(PRRS)is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus(PRRSV),resulting in substantial economic losses in the swine industry.Modifying the CD163 SRCR5 domain,either through deletion or substitution,can eff1ectively confer resistance to PRRSV infection in pigs.However,large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance.Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs.In the current study,we identified a specific functional amino acid in CD163 that influences PRRSV proliferation.Viral infection experiments conducted on Marc145 and PK-15CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV(HP-PRRSV)proliferation by preventing viral binding and entry.Furthermore,individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type(WT)pigs,confirming effective resistance to HP-PRRSV.Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs.These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs,providing novel insights into controlling future PRRSV outbreaks.

Statistical Channel Modeling for Indoor VLC Communications Based on Channel Measurements

Visible light communication(VLC)has attracted much attention in the research of sixthgeneration(6G)systems.Furthermore,channel modeling is the foundation for designing efficient and robust VLC systems.In this paper,we present extensive VLC channel measurement campaigns in indoor environments,i.e.,an office and a corridor.Based on the measured data,the large-scale fading characteristics and multipath-related characteristics,including omnidirectional optical path loss(OPL),K-factor,power angular spectrum(PAS),angle spread(AS),and clustering characteristics,are analyzed and modeled through a statistical method.Based on the extracted statistics of the above-mentioned channel characteristics,we propose a statistical spatial channel model(SSCM)capable of modeling multipath in the spatial domain.Furthermore,the simulated statistics of the proposed model are compared with the measured statistics.For instance,in the office,the simulated path loss exponent(PLE)and the measured PLE are 1.96and 1.97,respectively.And,the simulated medians of AS and measured medians of AS are 25.94°and 24.84°,respectively.Generally,the fact that the simulated results fit well with measured results has demonstrated the accuracy of our SSCM.

Improving creep strength of the fine-grained heat-affected zone of novel 9Cr martensitic heat-resistant steel via modified thermo-mechanical treatment

The infamous type Ⅳ failure within the fine-grained heat-affected zone (FGHAZ) in G115 steel weldments seriously threatens the safe operation of ultra-supercritical (USC) power plants.In this work,the traditional thermo-mechanical treatment was modified via the replacement of hot-rolling with cold rolling,i.e.,normalizing,cold rolling,and tempering (NCT),which was developed to improve the creep strength of the FGHAZ in G115 steel weldments.The NCT treatment effectively promoted the dissolution of preformed M_(23)C_(6)particles and relieved the boundary segregation of C and Cr during welding thermal cycling,which accelerated the dispersed reprecipitation of M_(23)C_(6) particles within the fresh reaustenitized grains during post-weld heat treatment.In addition,the precipitation of Cu-rich phases and MX particles was promoted evidently due to the deformation-induced dislocations.As a result,the interacting actions between precipitates,dislocations,and boundaries during creep were reinforced considerably.Following this strategy,the creep rupture life of the FGHAZ in G115 steel weldments can be prolonged by 18.6%,which can further push the application of G115 steel in USC power plants.

A Hybrid Machine Learning Approach for Improvised QoE in Video Services over 5G Wireless Networks

Video streaming applications have grown considerably in recent years.As a result,this becomes one of the most significant contributors to global internet traffic.According to recent studies,the telecommunications industry loses millions of dollars due to poor video Quality of Experience(QoE)for users.Among the standard proposals for standardizing the quality of video streaming over internet service providers(ISPs)is the Mean Opinion Score(MOS).However,the accurate finding of QoE by MOS is subjective and laborious,and it varies depending on the user.A fully automated data analytics framework is required to reduce the inter-operator variability characteristic in QoE assessment.This work addresses this concern by suggesting a novel hybrid XGBStackQoE analytical model using a two-level layering technique.Level one combines multiple Machine Learning(ML)models via a layer one Hybrid XGBStackQoE-model.Individual ML models at level one are trained using the entire training data set.The level two Hybrid XGBStackQoE-Model is fitted using the outputs(meta-features)of the layer one ML models.The proposed model outperformed the conventional models,with an accuracy improvement of 4 to 5 percent,which is still higher than the current traditional models.The proposed framework could significantly improve video QoE accuracy.

Unmet needs in biomarkers for autoimmune pancreatitis diagnosis

Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.

Understanding autoimmune pancreatitis: Clinical features, management challenges, and association with malignancies

In this editorial we comment on the article by Jaber et al.Autoimmune pancreatitis(AIP)represents a distinct form of pancreatitis,categorized into AIP-1 and AIP-2,characterized by obstructive jaundice,lymphoplasmacytic infiltrate,and fibrosis.AIP-1,associated with elevated immunoglobulin G4(IgG4)levels,exhibits higher relapse rates,affecting older males,while AIP-2 is less common and linked to inflammatory bowel disease.AIP is considered a manifestation of IgG4-related systemic disease,sharing characteristic histological findings.Steroids are the primary treatment,with emerging biomarkers like interferon alpha and inter-leukin-33.AIP poses an increased risk of various malignancies,and the assoc-iation with pancreatic cancer is debated.Surgery is reserved for severe cases,necessitating careful evaluation due to diagnostic challenges.AIP patients may have concurrent PanINs but display favorable long-term outcomes compared to pancreatic cancer patients.Thorough diagnostic assessment,including biopsy and steroid response,is crucial for informed surgical decisions in AIP.

A Probabilistic Trust Model and Control Algorithm to Protect 6G Networks against Malicious Data Injection Attacks in Edge Computing Environments

Future 6G communications are envisioned to enable a large catalogue of pioneering applications.These will range from networked Cyber-Physical Systems to edge computing devices,establishing real-time feedback control loops critical for managing Industry 5.0 deployments,digital agriculture systems,and essential infrastructures.The provision of extensive machine-type communications through 6G will render many of these innovative systems autonomous and unsupervised.While full automation will enhance industrial efficiency significantly,it concurrently introduces new cyber risks and vulnerabilities.In particular,unattended systems are highly susceptible to trust issues:malicious nodes and false information can be easily introduced into control loops.Additionally,Denialof-Service attacks can be executed by inundating the network with valueless noise.Current anomaly detection schemes require the entire transformation of the control software to integrate new steps and can only mitigate anomalies that conform to predefined mathematical models.Solutions based on an exhaustive data collection to detect anomalies are precise but extremely slow.Standard models,with their limited understanding of mobile networks,can achieve precision rates no higher than 75%.Therefore,more general and transversal protection mechanisms are needed to detect malicious behaviors transparently.This paper introduces a probabilistic trust model and control algorithm designed to address this gap.The model determines the probability of any node to be trustworthy.Communication channels are pruned for those nodes whose probability is below a given threshold.The trust control algorithmcomprises three primary phases,which feed themodel with three different probabilities,which are weighted and combined.Initially,anomalous nodes are identified using Gaussian mixture models and clustering technologies.Next,traffic patterns are studied using digital Bessel functions and the functional scalar product.Finally,the information coherence and content are analyzed.The noise content and abnormal information sequences are detected using a Volterra filter and a bank of Finite Impulse Response filters.An experimental validation based on simulation tools and environments was carried out.Results show the proposed solution can successfully detect up to 92%of malicious data injection attacks.

Distributed Application Addressing in 6G Network

To ensure the extreme performances of the new 6G services,applications will be deployed at deep edge,resulting in a serious challenge of distributed application addressing.This paper traces back the latest development of mobile network application addressing,analyzes two novel addressing methods in carrier network,and puts forward a 6G endogenous application addressing scheme by integrating some of their essence into the 6G network architecture,combining the new 6G capabilities of computing&network convergence,endogenous intelligence,and communication-sensing integration.This paper further illustrates how that the proposed method works in 6G networks and gives preliminary experimental verification.

A Novel 6G Scalable Blockchain Clustering-Based Computer Vision Character Detection for Mobile Images

6G is envisioned as the next generation of wireless communication technology,promising unprecedented data speeds,ultra-low Latency,and ubiquitous Connectivity.In tandem with these advancements,blockchain technology is leveraged to enhance computer vision applications’security,trustworthiness,and transparency.With the widespread use of mobile devices equipped with cameras,the ability to capture and recognize Chinese characters in natural scenes has become increasingly important.Blockchain can facilitate privacy-preserving mechanisms in applications where privacy is paramount,such as facial recognition or personal healthcare monitoring.Users can control their visual data and grant or revoke access as needed.Recognizing Chinese characters from images can provide convenience in various aspects of people’s lives.However,traditional Chinese character text recognition methods often need higher accuracy,leading to recognition failures or incorrect character identification.In contrast,computer vision technologies have significantly improved image recognition accuracy.This paper proposed a Secure end-to-end recognition system(SE2ERS)for Chinese characters in natural scenes based on convolutional neural networks(CNN)using 6G technology.The proposed SE2ERS model uses the Weighted Hyperbolic Curve Cryptograph(WHCC)of the secure data transmission in the 6G network with the blockchain model.The data transmission within the computer vision system,with a 6G gradient directional histogram(GDH),is employed for character estimation.With the deployment of WHCC and GDH in the constructed SE2ERS model,secure communication is achieved for the data transmission with the 6G network.The proposed SE2ERS compares the performance of traditional Chinese text recognition methods and data transmission environment with 6G communication.Experimental results demonstrate that SE2ERS achieves an average recognition accuracy of 88%for simple Chinese characters,compared to 81.2%with traditional methods.For complex Chinese characters,the average recognition accuracy improves to 84.4%with our system,compared to 72.8%with traditional methods.Additionally,deploying the WHCC model improves data security with the increased data encryption rate complexity of∼12&higher than the traditional techniques.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated surgi-cally.We studied the diagnosis and treatment of a patient with type 1 AIP recent-ly admitted to our hospital,and reviewed the literature to provide a reference for clinical diagnosis of AIP.CASE SUMMARY The chief complaint was yellowing of the body,eyes and urine for 21 d.The pa-tient's clinical presentation was obstructive jaundice and imaging suggested pan-creatic swelling.It was difficult to distinguish between inflammation and tumor.Serum immunoglobulin G4(IgG4)was markedly elevated.IgG4 is an important serological marker for type 1 AIP.The patient was diagnosed with AIP,IgG4-related cholangitis,acute cholecystitis and hepatic impairment.After applying hormonal therapy,the patient's symptoms improved significantly.At the same time,imaging suggested that pancreatic swelling subsided,and liver function and other biochemical indicators decreased.The treatment was effective.CONCLUSION In patients with pancreatic swelling,the possibility of AIP should be considered.

Historical tillage promotes grass-legume mixtures establishment and accelerates soil microbial activity and organic carbon decomposition

Perennial grass-legume mixtures have been extensively used to restore degraded grasslands,increasing grassland productivity and forage quality.Tillage is crucial for seedbed preparation and sustainable weed management for the establishment of grass-legume mixtures.However,a common concern is that intensive tillage may alter soil characteristics,leading to losses in soil organic carbon(SOC).We investigated the plant community composition,SOC,soil microbial biomass carbon(MBC),soil enzyme activities,and soil properties in long-term perennial grass-legume mixtures under two different tillage intensities(once and twice)as well as in a fenced grassland(FG).The establishment of grass-legume mixtures increased plant species diversity and plant community coverage,compared with FG.Compared with once tilled grassland(OTG),twice tilled grassland(TTG)enhanced the coverage of high-quality leguminous forage species by 380.3%.Grass-legume mixtures with historical tillage decreased SOC and dissolved organic carbon(DOC)concentrations,whereas soil MBC concentrations in OTG and TTG increased by 16.0%and 16.4%,respectively,compared with FG.TTG significantly decreased the activity of N-acetyl-β-D-glucosaminidase(NAG)by 72.3%,whereas soil enzymeβ-glucosidase(βG)in OTG and TTG increased by 55.9%and 27.3%,respectively,compared with FG.Correlation analysis indicated a close association of the increase in MBC andβG activities with the rapid decline in SOC.This result suggested that MBC was a key driving factor in soil carbon storage dynamics,potentially accelerating soil carbon cycling and facilitating biogeochemical cycling.The establishment of grass-legume mixtures effectively improves forage quality and boosts plant diversity,thereby facilitating the restoration of degraded grasslands.Although tillage assists in establishing legume-grass mixtures by controlling weeds,it accelerates microbial activity and organic carbon decomposition.Our findings provide a foundation for understanding the process and effectiveness of restoration management in degraded grasslands.

Analysis on unit maximum capacity of orthogonal multiple watermarking for multimedia signals in B5G wireless communications

Beyond-5G(B5G)aims to meet the growing demands of mobile traffic and expand the communication space.Considering that intelligent applications to B5G wireless communications will involve security issues regarding user data and operational data,this paper analyzes the maximum capacity of the multi-watermarking method for multimedia signal hiding as a means of alleviating the information security problem of B5G.The multiwatermarking process employs spread transform dither modulation.During the watermarking procedure,Gram-Schmidt orthogonalization is used to obtain the multiple spreading vectors.Consequently,multiple watermarks can be simultaneously embedded into the same position of a multimedia signal.Moreover,the multiple watermarks can be extracted without affecting one another during the extraction process.We analyze the effect of the size of the spreading vector on the unit maximum capacity,and consequently derive the theoretical relationship between the size of the spreading vector and the unit maximum capacity.A number of experiments are conducted to determine the optimal parameter values for maximum robustness on the premise of high capacity and good imperceptibility.

Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

SENEX-mediated CDK4/6 inhibition promotes senescence and confers apoptosis resistance in B-cell non-Hodgkin lymphoma

Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a crucial mechanism contributing to tumor drug resistance.Here,we analyzed SENEX/Rho GTPase Activating Protein 18(ARHGAP18)expression and prognostic significance in doxorubicin-induced B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL cell senescence and the effect of combining specific inhibitors on apoptosis resistance in B-NHL-TIS cells.Methods:Raji cells were transfected with the human SENEX shRNA recombinant lentiviral vector(Sh-SENEX)and the empty vector negative(NC)to construct a stable transfection cell line with knockdown of SENEX.Effect of SENEX-silencing on B-NHL-TIS formation,cell function and cell cycle-related pathways was analyzed.Using doxorubicin(DOX)-inducible senescent B-NHL cells combined with the specific cyclin dependent kinase 4/6(CDK4/6)inhibitor Palbociclib to observe that blocking CDK4/6 effects on TIS formation.SENEX expression of 21 B-NHL patients and 8 healthy controls were analyzed by qRT-PCR,and the correlation between its expression and clinical indicators were evaluated.Results:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting cell proliferation,collectively suppressing the formation of TIS in B-NHL.Blockade of CDK4/6 promotes the DOX-induced G1 phase arrest to enhance TIS formation in B-NHL cells which can reverse the regulatory effect of silencing SENEX on B-NHL cell cycle regulation and senescence.The expression levels of SENEX were notably elevated in B-NHL patients compared to healthy controls,and Elevated expression levels of SENEX were associated with poor prognosis of B-NHL patients.Conclusions:SENEX enhances apoptosis resistance in B-NHL by inhibiting CDK4/6,thereby preventing G1-S phase transition and promoting TIS formation.

APOBEC3G Role on HIV Infection in Africa: A Systematic Review

The highly active antiretroviral treatment (HAART) has allowed people living with HIV to live longer with a better quality of life. However, toxicity and the emergence of drug resistance arise from HAART use. Therefore, new antiretroviral therapy is needed since no cure or vaccine is available against HIV. Virus-host interaction has been proven to be important in the last decade. Host factors such as the C-C chemokine receptor type 5 (CCR5), a receptor used by HIV to penetrate host cells, have led to the discovery of the Maraviroc, which is an antiretroviral medication used in the United States. In contrast, other factors like C-X-C Motif Chemokine Receptor 4 (CXCR4) and the Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G), a potent host defense factor against HIV, is under investigation. APOBEC3G antiviral activity remains a possible therapeutic target against HIV. This systematic review aimed to synthesize the available evidence on the role of APOBEC3G polymorphisms and their expression on HIV infection disease progression in Africa. We used Web of Science, PubMed, Embase, and Google Scholar and searched for relevant publications in French or English reporting on APOBEC3G polymorphisms association with HIV infection in African populations from January 2009 to May 2023. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyzes) was used to process for reporting systematic review. Fifteen studies were included, of which seven were on APOBEC3G polymorphisms and eight were on APOBEC3G expression. Among the APOBEC3G polymorphisms, the most studied was H186R or rs8177832. The average of the minor allele frequency of H186R of APOBEC3G available for the studies included in this study was 0.29 with a 95% CI (0.172;0.401) and varied from 0.108 reported in Uganda to 0.47 recorded from Burkina Faso. The polymorphism H186R was not associated with HIV status in Southern Africa. However, the referent allele of H186R was protective against HIV infection in Western Central Africa, while in West Africa, it was the minor allele (G) of H186R which was protective against HIV. This review warrants a need to increase research on APOBEC3G, from its variants to its hypermutations on the continent with an essential variety of HIV-1 subtypes, to impact the research on A3G-based anti-HIV strategies.