Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against global virulence factor regulator Vfr.

is a leading cause of hospital-acquired infections. Treatment of infections is difficult given its multiple virulence mechanisms, intrinsic antibiotic resistance mechanisms, and biofilm-forming ability. Auranofin, an approved oral gold compound for rheumatoid arthritis treatment, was recently reported to inhibit the growth of multiple bacterial species.

Malonylation of Acetyl-CoA carboxylase 1 promotes hepatic steatosis and is attenuated by ketogenic diet in NAFLD.

Protein post-translational modifications (PTMs) participate in important bioactive regulatory processes and therefore can help elucidate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the involvement of PTMs in ketogenic diet (KD)-improved fatty liver by multi-omics and reveal a core target of lysine malonylation, acetyl-coenzyme A (CoA) carboxylase 1 (ACC1). ACC1 protein levels and Lys1523 malonylation are significantly decreased by KD.

Functionalized Rhodium Nanoparticles as Antimicrobial Agents for Treatment of Drug-Resistant Skin and Soft Tissue Infections.

Skin and soft tissue infections (SSTIs) are among the most common bacterial infections reported in outpatients. Drug-resistant bacteria are the major cause of treatment failure and increased mortality rate in patients with SSTIs, posing significant challenges to human health. In this study, new-generation rhodium nanoplates (RhNPs) and glycol chitosan- and polydopamine-functionalized RhNPs (Rh@GCS) are developed for the treatment of drug-resistant SSTIs.

Cell division factor ZapE regulates biofilm formation by impacting the quorum sensing system.

is one of the leading nosocomial pathogens that causes both severe acute and chronic infections. The strong capacity of to form biofilms can dramatically increase its antibiotic resistance and lead to treatment failure. The biofilm resident bacterial cells display distinct gene expression profiles and phenotypes compared to their free-living counterparts.

is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway.

The mechanisms of self-renewal and pluripotency maintenance of human pluripotent stem cells (hPSCs) have not been fully elucidated, especially for the role of those poorly characterized long noncoding RNAs (lncRNAs). is a lncRNA highly expressed in hPSCs, and its functional roles are being extensively explored in the field. Here, we identified that the transcription of can be directly regulated by OCT4, a key self-renewal factor in hPSCs.

Identification of an unfolded protein response-related signature for predicting the prognosis of pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy. An effective prognosis prediction model is urgently needed for treatment optimization.

Methods: The differentially expressed unfolded protein response (UPR)‒related genes between pancreatic tumor and normal tissue were analyzed using the TCGA-PDAC dataset, and these genes that overlapped with UPR‒related prognostic genes from the E-MTAB-6134 dataset were further analyzed.

Low rate of pre-exposure prophylaxis and post-exposure prophylaxis uptake and high prevalence of transmitted drug resistance among newly diagnosed primary HIV infections in Shenzhen, China: a real-world retrospective study.

Background: Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen.

Methods: This is a real-world retrospective study.

Improper preanalytical processes on peripheral blood compromise RNA quality and skew the transcriptional readouts of mRNA and LncRNA.

Genetic and epigenetic reprogramming caused by disease states in other tissues is always systemically reflected in peripheral blood leukocytes (PBLs). Accurate transcriptional readouts of Messenger RNA (mRNA) and Long non-coding RNA (lncRNA) in peripheral blood leukocytes are fundamental for disease-related study, diagnosis and treatment. However, little is known about the impact of preanalytical variables on RNA quality and downstream messenger RNA and Long non-coding RNA readouts.

Time of Liver Function Abnormal Identification on Prediction of the Risk of Anti-tuberculosis-induced Liver Injury.

Background And Aims: Anti-tuberculosis (anti-TB) drug-induced liver injury (AT-DILI) is the most common side effect in patients who received anti-TB therapy. AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage. The present study aimed to investigate the effect of liver function test (LFT) abnormal identification on the risk of DILI, including liver failure and anti-TB drug resistance in patients without high-risk factors.

Sonodynamic therapy suppresses matrix collagen degradation in vulnerable atherosclerotic plaque by modulating caspase 3 - PEDF/HIF-1α - MMP-2/MMP-9 signaling in macrophages.

Background: The rupture of vulnerable atherosclerotic plaque is the main cause of acute ischemic vascular events, and is characterized by pathological degradation of matrix collagen in the fibrous cap. In a previous study, we reported that 5-aminolevulinic acid-mediated sonodynamic therapy suppressed collagen degradation in rabbit plaque. However, the underlying molecular mechanism has yet to be fully elucidated.

Acquisition of T6SS Effector TseL Contributes to the Emerging of Novel Epidemic Strains of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen with multiple strategies to interact with other microbes and host cells, gaining fitness in complicated infection sites. The contact-dependent type VI secretion system (T6SS) is one critical secretion apparatus involved in both interbacterial competition and pathogenesis. To date, only limited numbers of T6SS-effectors have been clearly characterized in P.

Immune microenvironment and therapeutic progress of recurrent hepatocellular carcinoma after liver transplantation.

HCC is a highly lethal tumor, and orthotopic liver transplantation, as one of the radical treatment methods for HCC, has opened-up a new therapeutic approach for the treatment of primary liver cancer. However, tumor recurrence after liver transplantation is the main reason that affects the long-term survival of recipients. At present, the application of ICIs has brought dawn to patients with refractory HCC.

Xpert MTB/RIF Ultra in the auxiliary diagnosis of tuberculosis among people living with human immunodeficiency virus.

Clinical diagnosis of tuberculosis (TB) in people living with the human immunodeficiency virus (HIV) poses a challenge. The Xpert MTB/RIF Ultra (Ultra) has displayed greater sensitivity at diagnosing tuberculosis and rifampicin resistance compared to the Xpert MTB/RIF (Xpert). However, whether Ultra is able to facilitate an auxiliary diagnosis of TB in patients with an HIV-TB co-infection remains unclear.

Association of human cytomegalovirus in urine with end-organ diseases in stage 2/3 HIV-1-infected individuals.

Background: Human cytomegalovirus (HCMV) is prevalent in human immunodeficiency virus type 1 (HIV-1)-infected individuals but is suppressed by the host immune system bolstered by antiretroviral therapy. During stage 4 of HIV-1 infection, HCMV becomes a major risk factor for end-organ diseases (EODs). However, the implications of detecting HCMV in patients with stage 2/3 HIV-1 infection have not been established.

Young MSM changed temporal HIV-1 epidemic pattern in Heilongjiang Province, China.

Background: Human immunodeficiency virus type 1 (HIV-1) epidemic in China is featured by geographical diversity of epidemic patterns. Understanding the characteristics of regional HIV-1 epidemic allows carrying out targeted prevention and controlling measures. This seven-year cross-sectional study was conducted in Heilongjiang, one province of Northeast China, where newly diagnosed infection is fast increasing yearly, but temporal HIV-1 epidemic trend is largely unknown.

RUNX Proteins as Epigenetic Modulators in Cancer.

RUNX proteins are highly conserved in metazoans and perform critical functions during development. Dysregulation of RUNX proteins through various molecular mechanisms facilitates the development and progression of various cancers, where different RUNX proteins show tumor type-specific functions and regulate different aspects of tumorigenesis by cross-talking with different signaling pathways such as Wnt, TGF-β, and Hippo. Molecularly, they could serve as transcription factors (TFs) to activate their direct target genes or interact with many other TFs to modulate chromatin architecture globally.

Spatial metabolomics on liver cirrhosis to hepatocellular carcinoma progression.

Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers and is mainly developed from chronic liver diseases such as hepatitis-B infection-associated liver cirrhosis (LC). The progression from LC to HCC makes the detection of diagnostic biomarkers to be challenging. Hence, there have been constant efforts to improve on identifying the critical and predictive changes accompanying the disease progression.

Topological approach of liver segmentation based on 3D visualization technology in surgical planning for split liver transplantation.

Background: Split liver transplantation (SLT) is a complex procedure. The left-lateral and right tri-segment splits are the most common surgical approaches and are based on the Couinaud liver segmentation theory. Notably, the liver surface following right tri-segment splits may exhibit different degrees of ischemic changes related to the destruction of the local portal vein blood flow topology.

Reconstructing the portal vein through a posterior pancreatic tunnel: New choice for portal vein thrombosis during liver transplantation.

Background: Thrombectomy and anatomical anastomosis (TAA) has long been considered the optimal approach to portal vein thrombosis (PVT) in liver transplantation (LT). However, TAA and the current approach for non-physiological portal reconstructions are associated with a higher rate of complications and mortality in some cases.

Aim: To describe a new choice for reconstructing the portal vein through a posterior pancreatic tunnel (RPVPPT) to address cases of unresectable PVT.

A rapid bacterial pathogen and antimicrobial resistance diagnosis workflow using Oxford nanopore adaptive sequencing method.

Metagenomic sequencing analysis (mNGS) has been implemented as an alternative approach for pathogen diagnosis in recent years, which is independent of cultivation and is able to identify all potential antibiotic resistance genes (ARGs). However, current mNGS methods have to deal with low amounts of prokaryotic deoxyribonucleic acid (DNA) and high amounts of host DNA in clinical samples, which significantly decrease the overall microbial detection resolution. The recently released nanopore adaptive sampling (NAS) technology facilitates immediate mapping of individual nucleotides to a given reference as each molecule is sequenced.

Inhibition of HSPA8 by rifampicin contributes to ferroptosis via enhancing autophagy.

Background And Aim: Rifampicin is the most common pathogenic factor in anti-tuberculosis drug-induced liver injury (AT-DILI), the mechanisms that it promotes hepatocyte damage in AT-DILI are not yet to be thoroughly elucidated. In this study, we investigated the potential molecular mechanisms for ferroptosis involving rifampicin hepatotoxicity.

Methods: Animal and cell injury models of rifampicin were constructed, and the toxicity of rifampicin was assessed by physicochemical staining and cell viability assay.

Naturally occurring spike mutations influence the infectivity and immunogenicity of SARS-CoV-2.

Mutations in SARS-CoV-2 variants of concern (VOCs) have enhanced transmissibility and immune evasion with respect to current vaccines and neutralizing antibodies (NAbs). How naturally occurring spike mutations affect the infectivity and antigenicity of VOCs remains to be investigated. The entry efficiency of individual spike mutations was determined in vitro using pseudotyped viruses.

Significance of initiating antiretroviral therapy in the early stage of HIV infection.

A growing number of guidelines now recommend that human immunodeficiency virus (HIV) infected patients should be given early antiretroviral therapy (ART), especially in acute HIV infection. ART during early infection can limit viral reservoirs and improve immune cell function. From a societal prospect, early-infected individuals who achieve a state of viral suppression through ART can reduce the chance of HIV transmission and reduce the acquired immunodeficiency syndrome (AIDS)-related disease burden.

Lineage-specific positive selection on contributes to the genetic susceptibility of COVID-19.

The Angiotensin-Converting Enzyme-2 () gene, located on Xp22.2, attracts a great deal of attention because the protein it encodes is believed to be the functional cellular receptor for the new coronavirus (SARS-CoV-2). However, recent studies are controversial, especially concerning the intrinsic link between diversity and COVID-19 susceptibility.