TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation

Tripartite motif containing 22 （TRIM22）, a member of the TRIM/RBCC family, has been reported to activate the nuclear factor-kappa B （NF-kB） pathway in unstimulated macrophage cell lines, but the detailed mechanisms governing this activation remains unclear. We investigated this mechanism in HEK293T cells. We found that overexpression of TRIM22 could activate the NF-kB pathway and conversely, could inhibit the tumor necrosis factor receptor-associated factor 6 （TRAF6）-stimulated NF-kB pathway in HEK293T cells. Further experiments showed that TRIM22 could decrease the self-ubiquitination of TRAF6, and interact with and degrade transforming growth factor-13 activated kinase 1 binding protein 2 （TAB2）, and that these effects could be partially rescued by a TRIM22 RING domain deletion mutant. Collectively, our data indicate that overexpression of TRIM22 may negatively regulate the TRAF6-stimulated NF-rd3 pathway by interacting with and degrading TAB2.

Diagnostic accuracy of tests for Helicobacter pylori in an Alaska Native population

AIM： TO evaluate the accuracy of two non-invasive tests in a population of Alaska Native persons. High rates of Helicobacter pylori （H. pylon] infection, H. pyIori treatment failure, and gastric cancer in this population necessitate documentation of infection status at multiple time points over a patient＇s life.urease test, 13C urea breath test （UBT）, and immunoglobulin G antibodies to H. pylori in serum. The performances of 13C-UBT and antibody test were compared to a gold standard defined by a positive H. pylori test by culture or, in case of a negative culture result, by positive histology and a positive rapid urease test.RESULTS： The sensitivity and specificity of the 13C- UBT were 93% and 88%, respectively, relative to the gold standard. The antibody test had an equivalent sensitivity of 93% with a reduced specificity of 68%. The false positive results for the antibody test were associated with previous treatment for an H. pylorlinfection [relative risk （RR） = 2.8]. High levels of antibodies to H. py/or/were associated with chronic gastritis and male gender, while high scores in the 13C-UBT test were associated with older age and with theH. pylori bacteria load on histological examination （RR = 4.4）. CONCLUSION： The 13C-UBT outperformed the antibody test for H. pylori and could be used when a noninvasive test is clinically necessary to document treatment outcome or when monitoring for reinfection.

Prevalence of ocular demodicosis among patients at Tertiary Care Center,Bangkok,Thailand

AIM： To determine the prevalence of ocular demodicosis by both microscopic examination and molecular detection among patients at King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok.METHODS： One hundred individuals were enrolled in the study and were divided into five age groups. The meibomian gland dysfunction （MGD） score and qualities of cylindrical dandruff （CD） were also determined. Demodex mite infestations of eyelash samples were screened by both microscopic examination and semi-nested polymerase chain reaction （PCR）. RESULTS： The prevalence of ocular demodicosis as determined by microscopic examination was 42% [Demodex folliculorum （D. folliculorum） 41% and Demodex brevis （D. brevis） 1%]. Among patients who had ocular Demodex infestation, 69% have CD and had an average MGD score of 4; in patients without demodicosis, 15.5% had CD and had an average MGD score of 4.12. Prevalence of ocular demodicosis as determined by semi-nested PCR was 79% （D. folliculorum 78% and D. brevis 1%）.CONCLUSION： This is the first report on the prevalence of ocular demodicosis in Thailand. Patients with CD also had Demodex mites present. Semi-nested PCR is better than microscopy for Demodex infestation detection. An extensive survey with more representative samples is required to determine the prevalence in the country.

Real-time quantitative PCR assay for rapid detection of murine virus contamination in bioproducts

Dear Editor,For decades,contaminated and misidentified cell lines in biological research remains a serious problem which the researchers call it"identity crisis"(Masters J R,2009).As reported in March 15,2010 by U.S.Food

Human Monoclonal Antibodies as Candidate Therapeutics Against Emerging Viruses and HIV-1

More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.

Molecular dissection of phage lysin PlySs2: integrity of the catalytic and cell wall binding domains is essential for its broad lytic activity

The novel phage lysin PlySs2, is reported to be highly active against various bacteria, including staphylococci, streptococci and Listeria. However, the molecular mechanisms underlying its broad lytic spectrum remain to be established. In the present study, the lytic activity of the catalytic domain(CD, PlySc) and binding specificity of the cell wall binding domain(CBD, PlySb) of PlySs2 were examined. Our results showed that PlySc alone maintains very limited lytic activity. Enhanced green fluorescent protein(EGFP)-fused PlySb displayed high binding affinity to the streptococcal strains tested, including S.suis, S.dysgalactiae, and S.agalactiae, but not staphylococci, supporting its utility as a good CBD donor for streptococcal-targeted lysin engineering. EGFP-fused intact PlySs2 similarly displayed high affinity for streptococci, but not staphylococci. Notably, four truncated PlySb fragments showed no binding capacity. These findings collectively indicate that integrity of the PlySc and PlySb domains is an essential determinant of the broad lytic activity of PlySs2.

Formation of Co-implanted Silicon Ultra-Shallow Junctions for Low Thermal Budget Applications

We present a systematic study to create ultra-shallow junctions in n-type silicon substrates and investigate both pre-and post-annealing processes to create a processing strategy for potential applications in nano-devices.Starting wafers were co-implanted with indium and C atoms at energies of 70 keV and 10 keV,respectively.A carefully chosen implantation schedule provides an abrupt ultra-shallow junction between 17 and 43 nm with suppressed sheet resistance and appropriate retained sheet carrier concentration at low thermal budget.A defect doping matrix,primarily the behavior and movement of co-implant generated interstitials at different annealing temperatures,may be engineered to form sufficiently activated ultra-shallow devices.

Gender medicine:Lessons from COVID-19 and other medical conditions for designing health policy

Gender-specific differences in the prevalence,incidence,comorbidities,prognosis,severity,risk factors,drug-related aspects and outcomes of various medical conditions are well documented.We present a literature review on the extent to which research in this field has developed over the years,and reveal gaps in gender-sensitive awareness between the clinical portrayal and the translation into gender-specific treatment regimens,guidelines and into gender-oriented preventive strategies and health policies.Subsequently,through the lens of gender,we describe these domains in detail for four selected medical conditions:Asthma,obesity and overweight,chronic kidney disease and coronavirus disease 2019.As some of the key gender differences become more apparent during adolescence,we focus on this developmental stage.Finally,we propose a model which is based on three influential issues:(1)Investigating gender-specific medical profiles of related health conditions,rather than a single disease;(2)The dynamics of gender disparities across developmental stages;and(3)An integrative approach which takes into account additional risk factors(ethnicity,socio-demographic variables,minorities,lifestyle habits etc.).Increasing the awareness of gender-specific medicine in daily practice and in tailored guidelines,already among adolescents,may reduce inequities,facilitate the prediction of future trends and properly address the characteristics and needs of certain subpopulations within each gender.

Towards efficient generative AI and beyond-AI computing:New trends on ISSCC 2024 machine learning accelerators

Compared to the last decade when the convolution neu-ral network(CNN)dominated the research field,machine learn-ing(ML)algorithms have reached a pivotal moment called the generative artificial intelligence(AI)era.With the emer-gence of large-scale foundation models[1],such as large multi-modal model(LMM)GPT-4[2]and text-to-image generative model DALL·E[3].

Vascular medicine in the 21st century:Embracing comprehensive vasculature evaluation and multidisciplinary treatment

The field of vascular medicine has undergone a profound transformation in the 21st century,transforming our approach to assessment and treatment.Athero-sclerosis,a complex inflammatory disease that affects medium and large arteries,presents a major challenge for researchers and healthcare professionals.This condition,characterized by arterial plaque formation and narrowing,poses sub-stantial challenges to vascular health at individual,national,and global scales.Its repercussions are far-reaching,with clinical outcomes including ischemic heart disease,ischemic stroke,and peripheral arterial disease—conditions with esca-lating global prevalence.Early detection of vascular changes caused by athero-sclerosis is crucial in preventing these conditions,reducing morbidity,and averting mortality.This article underscored the imperative of adopting a holistic approach to grappling with the intricacies,trajectories,and ramifications of atherosclerosis.It stresses the need for a thorough evaluation of the vasculature and the implementation of a multidisciplinary treatment approach.By consi-dering the entire vascular system,healthcare providers can explore avenues for prevention,early detection,and effective management of this condition,ultima-tely leading to improved patient outcomes.We discussed current practices and proposed new directions made possible by emerging diagnostic modalities and treatment strategies.Additionally,we considered healthcare expenditure,resour-ce allocation,and the transformative potential of new innovative treatments and technologies.

美国耐甲氧西林金黄色葡萄球菌感染治疗临床治疗指南(一)

美国感染病学会（IDSA）制订了治疗耐甲氧西林金黄色葡萄球菌（MRSA）患者的循证指南。该指南用于指导MRSA感染患者的治疗。该指南就多种与MRSA疾病相关的临床症状的治疗进行了论述,包括：皮肤和软组织感染（SSTI）、菌血症和感染性心内膜炎、肺炎、骨和关节感染、中枢神经系统（CNS）感染等。该指南重点介绍了关于万古霉素用量及监测,以及对万古霉素低敏的耐甲氧西林金黄色葡萄球菌菌株感染的治疗方案及治疗失败的处置。

Viral Metagenomics Analysis of Planktonic Viruses in East Lake,Wuhan,China

East Lake(Lake Donghu),located in Wuhan,China,is a typical city freshwater lake that has been experiencing eutrophic conditions and algal blooming during recent years.Marine and fresh water are considered to contain a large number of viruses.However,little is known about their genetic diversity because of the limited techniques for culturing viruses.In this study,we conducted a viral metagenomic analysis using a high-throughput sequencing technique with samples collected from East Lake in Spring,Summer,Autumn,and Winter.The libraries from four samples each generated 234,669,71,837,12,820,and 34,236 contigs(>90 bp each),respectively.The genetic structure of the viral community revealed a high genetic diversity covering 23 viral families,with the majority of contigs homologous to DNA viruses,including members of Myoviridae,Podoviridae,Siphoviridae,Phycodnaviridae,and Microviridae,which infect bacteria or algae,and members of Circoviridae,which infect invertebrates and vertebrates.The highest viral genetic diversity occurred in samples collected in August,then December and June,and the least diversity in March.Most contigs have low-sequence identities with known viruses.PCR detection targeting the conserved sequences of genes(g20,psbA,psbD,and DNApol)of cyanophages further confirmed that there are novel cyanophages in the East Lake.Our viral metagenomic data provide the first preliminary understanding of the virome in one freshwater lake in China and would be helpful for novel virus discovery and the control of algal blooming in the future.

Rapid quantification of semen hepatitis B virus DNA by real-time polymerase chain reaction

AIM： To examine the sensitivity and accuracy of real-time polymerase chain reaction （PCR） for the quantification of hepatitis B virus （HBV） DNA in semen. METHODS： Hepatitis B viral DNA was isolated from HBV carriers＇ semen and sera using phenol extraction method and QIAamp DNA blood mini kit （Qiagen, Germany）. HBV DNA was detected by conventional PCR and quantified by TaqMan technology-based real-time PCR （quantitative polymerase chain reaction （qPCR））. The detection threshold was 200 copies of HBV DNA for conventional PCR and 10 copies of HBV DNA for real time PCR per reaction. RESULTS： Both methods of phenol extraction and QIAamp DNA blood mini kit were suitable for isolating HBV DNA from semen. The value of the detection thresholds was 500 copies of HBV DNA per mL in the semen. The viral loads were 7.5×10^7 and 1.67×10^7 copies of HBV DNA per mL in two HBV infected patients＇ sera, while 2.14×10^5 and 3.02×10^5 copies of HBV DNA per mL in the semen. CONCLUSION： Real-time PCR is a more sensitive and accurate method to detect and quantify HBV DNA in the semen.

Macrophage migration inhibitory factor as a potential prognostic factor in gastric cancer

AIM:To investigate macrophage migration inhibitory factor(MIF) expression and its clinical relevance in gastric cancer,and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS:Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry(IHC) semiquantitatively,and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcriptionpolymerase chain reaction(RT-PCR) and Western blot. Two pairs of si RNA targeting the MIF gene(MIF si-1 and MIF si-2) and one pair of scrambled si RNA as a negative control(NC) were designed and chemically synthesized. All si RNAs were transiently transfected in AGS cells with OligofectamineTM to knock down the MIF expression,with the NC group and mock group(OligofectamineTM alone) as controls. At 24,48,and 72 h after transfection,MIF m RNA was analyzed by RTPCR,and MIF and proliferating cell nuclear antigen(PCNA) proteins were detected by Western blot.The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium(MTT) assay and colony forming assay.RESULTS:The tissue microarray was informative for IHC staining,in which the MIF expression in gastric cancer tissues was higher than that in adjacent noncancer normal tissues(P < 0.001),and high level of MIF was related to poor tumor differentiation,advanced T stage,advanced tumor stage,lymph node metastasis,and poor patient survival(P < 0.05 for all). After si RNA transfection,MIF m RNA was measured by real-time PCR,and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group,MIF expression was knocked down successfully in gastric cancer cells,and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection,and colonies formed were assayed by colony forming assay 10 d after transfection; all these showed significant changes in gastric cancer cells transfected with specific si RNA compared with the control si RNA and mock groups(P < 0.001 for all).CONCLUSION:MIF could be of prognostic value in gastric cancer and might be a potential target for small-molecule therapy.

Genetic variability of CYP2B6 polymorphisms in four southern Chinese populations

AIM： To investigate the genotype and allelic frequencies of Cytochrome P450 2B6 polymorphisms in four southern Chinese populations.METHODS： DNA was obtained from blood samples from Han Chinese from Hong Kong and three minority groups,the Wa, Bulang and Lahu from Yunnan in southern China. Genotyping was performed using real-time PCR and confirmed by direct sequencing.RESULTS： A total of 507 subjects from southern China were studied. Results showed there is a high prevalence of 516G 〉 T （34.5%） in ethnic Chinese compared to literature reports on other Asian populations and Caucasians. The frequency of the 516TT genotype is higher in the Hah majority （23.1%） than in three other ethnic minority groups （i.e., 7.4%, 9.1% and 15.8%） in southern China.CONCLUSION： This was the first study to document the spectrum of CYP2B6 allelic variants and genotypes in a southern Chinese population. The 516G 〉 T allele is associated with a defective metabolism of efavirenz （EFV）, which therefore may predispose to drug toxicity.Treatment regimens for human immunodeficiency virus （HIV） and heroin addiction may need to be optimized in different populations because of the marked variability of the key metabolizing enzyme.

Viral kinetics of Enterovirus 71 in human habdomyosarcoma cells

AIM:To characterise the viral kinetics of enterovirus 71 (EV71).METHODS:In this study,human rhabdomyosarcoma (RD) cells were infected with EV71 at different multiplicity of infection (MOI).After infection,the cytopathic effect (CPE) was monitored and recorded using a phase contrast microscope associated with a CCD camera at different time points post viral infection (0,6,12,24 h post infection).Cell growth and viability were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both EV71 infected and mock infected cells at each time point.EV71 replication kinet-ics in RD cells was determined by measuring the total intracellular viral RNA with real-time reverse-transcription polymerase chain reaction (qRT-PCR).Also,the intracellular and extracellular virion RNA was isolated and quantified at different time points to analyze the viral package and secretion.The expression of viral protein was determined by analyze the levels of viral structure protein VP1 with Western blotting.RESULTS:EV71 infection induced a significant CPE as early as 6 h post infection (p.i.) in both RD cells infected with high ratio of virus (MOI 10) and low ratio of virus (MOI 1).In EV71 infected cells,the cell growth was inhibited and the number of viable cells was rapidly decreased in the later phase of infection.EV71 virions were uncoated immediately after entry.The intracellular viral RNA began to increase at as early as 3 h p.i.and the exponential increase was found between 3 h to 6 h p.i.in both infected groups.For viral structure protein synthesis,results from western-blot showed that intracellular viral protein VP1 could not be detected until 6 h p.i.in the cells infected at either MOI 1 or MOI 10;and reached the peak at 9 h p.i.in the cells infected with EV71 at both MOI 1 and MOI 10.Simultaneously,the viral package and secretion were also actively processed as the virus underwent rapid replication.The viral package kinetics was comparable for both MOI 1 and MOI 10 infected groups.It was observed that at 3 h p.i,the intracellular virions obviously decreased,thereafter,the intracellular virions began to increase and enter into the exponential phase until 12 h p.i.The total amounts of intracellular virons were decreased from 12 to 24 h p.i.Consistent with this result,the increase of virus secretion occurred during 6 to 12 h p.i.CONCLUSION:The viral kinetics of EV71 were established by analyzing viral replication,package and secretion in RD cells.

Study of the Dynamics of Microcystis aeruginosa and its Cyanophage in East Lake using quantitative PCR

Dear Editor,East Lake,located in the middle and lower reaches of the Yangtze River,is a major source of drinking water for local residents.However,the large increase of population density and the rapid development of industry has resulted in heavy eutrophication of East Lake over the past few decades.Microcystis aeruginosa is a well-known

THE EVOLUTION OF FIELD DEPLOYABLE fNIR SPECTROSCOPY FROM BENCH TO CLINICAL SETTINGS

In the late 1980s and early 1990s,Dr.Britton Chance and his colleagues,using picosecond-long laser pulses,spearheaded the development of time-resolved spectroscopy techniques in an effort to obtain quantitative information about the optical characteristics of the tissue.These efforts by Chance and colleagues expedited the translation of near-infrared spectroscopy(NIRS)-based techniques into a neuroimaging modality for various cognitive studies.Beginning in the early 2000s,Dr.Britton Chance guided and steered the collaboration with the Optical Brain Imaging team at Drexel University toward the development and application of afield deployable continuous wave functional near-infrared spectroscopy(fNIR)system as a means to monitor cognitive functions,particularly during attention and working memory tasks as well as for complex tasks such as war games and air tra±c control scenarios performed by healthy volunteers under operational conditions.Further,these collaborative efforts led to various clinical applications,including traumatic brain injury,depth of anesthesia monitoring,pediatric pain assessment,and brain
computer interface in neurology.In this paper,we introduce how these collaborative studies have made fNIR an excellent candidate for specified clinical and research applications,including repeated cortical neuroimaging,bedside or home monitoring,the elicitation of a positive effect,and protocols requiring ecological validity.This paper represents a token of our gratitude to Dr.Britton Chance for his influence and leadership.Through this manuscript we show our appreciation by contributing to his commemoration and through our work we will strive to advance thefield of optical brain imaging and promote his legacy.

Viral hepatitis and human immunodeficiency virus coinfections in Asia

Hepatitis B virus(HBV), hepatitis C virus(HCV),and human immunodeficiency virus(HIV) affect many people in Asian countries, although there are geographic differences. Both HBV and HIV(HBV/HIV) and HCV/HIV co-infections are highly prevalent in Asia. Hetero- and homosexual, injection drug use, and geographic area are strong predictors of HBV, HCV, and HIV serostatus. In HBV endemic regions, the prevalence and genotype distribution of HBV/HIV coinfection is almost comparable with that in the general population. In Japan, where HBV has low endemicity, the prevalence of HBV/HIV co-infection is approximately 10-fold higher than that in the general population, and HBV Ae is the most common subgenotype among HIV infected individuals. Highly active antiretroviral therapy(HAART) is an effective treatment for HIV/Acquired Immune Deficiency Syndrome. Lamivudine, a component of HAART, is an effective treatment for HBV, HIV, and HBV/HIV co-infection; however, cost, emerging drug resistance, antiretroviral-associated liver toxicity and liver-related morbidity due to HCV progression are particular concerns. HCV/HIV co-infection may accelerate the clinical progression of both HCV and HIV. The high prevalence of HBV/HIV and HCV/HIV co-infections in Asia underscores the need to improve prevention and control measures, as fewer evidencebased prevention strategies are available(compared with Western countries). In this review, the most recent publications on the prevalence of HBV/HIV and HCV/HIV co-infections and related issues, such as therapy and problems in Asia, are updated and summarized.

Bayesian evolutionary analysis for emerging infectious disease:an exemplified application for H7N9 avian influenza viruses

Dear Editor,Ever since the first human infection with H7N9 avian influenza virus（AIV）was reported in China in March 2013,there have been five H7N9 AIV pandemics in humans.Wave5 began earlier than the previous four waves,spread to more districts and counties in affected provinces,and had more confirmed cases（Wang et al.,2017）.