DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer.

Hyperactivation of ribosome biogenesis (RiBi) drives cancer progression, yet the role of RiBi-associated proteins (RiBPs) in breast cancer (BC) is underexplored. In this study, we perform a comprehensive multi-omics analysis and reveal that assembly and maturation factors (AMFs), a subclass of RiBPs, are upregulated at both RNA and protein levels in BC, correlating with poor patient outcomes. In contrast, ribosomal proteins (RPs) do not show systematic upregulation across various cancers, including BC.

Design, synthesis, and structure-activity relationships of xanthine derivatives as broad-spectrum inhibitors of coronavirus replication.

Illuminated by insights into the hijacking of host cellular metabolism by coronaviruses, we identified an initial hit compound 7030B-C5, characterized by a xanthine scaffold, via a cellular-level phenotypic screening from a domestic repertoire of lipid-modulating agents. A series of derivatives were synthesized and optimized through comprehensive structure-activity relationship (SAR) studies focusing on the N-1, C-8, and N-7 positions of xanthine and preliminary exploration on the N-3 position and parent nucleus. Compounds 10e, 10f and 10o, featuring modifications at the N-7 position, showed inhibitory activity with half maximal effective concentration (EC) values in the three-digit nanomolar range against human coronavirus-229E (HCoV-229E).

The influence of occupant control behaviour on thermal comfort under different heating charging modes in residential buildings in cold regions.

In China's central heating, there are two modes for calculating heating costs, which are divided into Charging by flow mode which charges according to the amount of use and Charging by area mode which charges according to the floor area. The Charging by flow mode has been increasingly adopted by numerous urban central heating buildings. Thus it is worth investigating whether occupants experience varying levels of thermal comfort under these two modes.

UBE3C restricts EV-A71 replication by ubiquitination-dependent degradation of 2C.

Unlabelled: Ubiquitin modification of viral proteins to degrade or regulate their function is one of the strategies of the host to resist viral infection. Here, we report that ubiquitin protein ligase E3C (UBE3C), an E3 ubiquitin ligase, displayed inhibitory effects on EV-A71 replication. UBE3C knockdown resulted in increased viral protein levels and virus titers, whereas overexpression of UBE3C reduced EV-A71 replication.

Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex.

The ring-shaped Cohesin complex, consisting of core subunits Smc1, Smc3, Scc1, and SA2 (or its paralog SA1), topologically entraps two duplicated sister DNA molecules to establish sister chromatid cohesion in S-phase. It remains largely elusive how the Cohesin release factor Wapl binds the Cohesin complex, thereby inducing Cohesin disassociation from mitotic chromosomes to allow proper resolution and separation of sister chromatids. Here, we show that Wapl uses two structural modules containing the FGF motif and the YNARHWN motif, respectively, to simultaneously bind distinct pockets in the extensive composite interface between Scc1 and SA2.

hUCMSC-derived extracellular vesicles relieve cisplatin-induced granulosa cell apoptosis in mice by transferring anti-apoptotic miRNAs.

Premature ovarian insufficiency (POI) caused by chemotherapy is a common complication in female cancer survivors of childbearing age. Traditional methods including mesenchymal stem cell (MSC) transplant and hormone replacement therapy have limited clinical application due to their drawbacks, and more methods need to be developed. In the current study, the potential effects and underlying mechanisms of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) were investigated in a cisplatin (CDDP)-induced POI mouse model and a human granulosa cell (GC) line.

A non-canonical role of the inner kinetochore in regulating sister-chromatid cohesion at centromeres.

The 16-subunit Constitutive Centromere-associated Network (CCAN)-based inner kinetochore is well-known for connecting centromeric chromatin to the spindle-binding outer kinetochore. Here, we report a non-canonical role for the inner kinetochore in directly regulating sister-chromatid cohesion at centromeres. We provide biochemical, X-ray crystal structure, and intracellular ectopic localization evidence that the inner kinetochore directly binds cohesin, a ring-shaped multi-subunit complex that holds sister chromatids together from S-phase until anaphase onset.

Tribbles pseudokinase 3 promotes enterovirus A71 infection via dual mechanisms.

Enterovirus A71 (EV-A71) is the main pathogen causing hand, foot and mouth disease (HFMD) in children and occasionally associated with neurological diseases such as aseptic meningitis, brainstem encephalitis (BE) and acute flaccid paralysis. We report here that cellular pseudokinase tribbles 3 (TRIB3) facilitates the infection of EV-A71 via dual mechanisms. In one hand, TRIB3 maintains the metabolic stability of scavenger receptor class B member 2 (SCARB2), the receptor of EV-A71, to enhance the infectious entry and spreading of the virus.

The Chinese thermal comfort dataset.

Heating and cooling in buildings accounts for over 20% of total energy consumption in China. Therefore, it is essential to understand the thermal requirements of building occupants when establishing building energy codes that would save energy while maintaining occupants' thermal comfort. This paper introduces the Chinese thermal comfort dataset, established by seven participating institutions under the leadership of Xi'an University of Architecture and Technology.

Propofol suppresses OGD/R-induced ferroptosis in neurons by inhibiting the HIF-1α/YTHDF1/BECN1 axis.

Background: Ischemia/reperfusion (I/R) is a pathological process that causes severe damage. Propofol is known to alleviate I/R-related injury; however, the exact function and underlying mechanisms are not fully understood.

Methods: Using an oxygen glucose deprivation/re-oxygenation (OGD/R) method, an I/R injury model was induced.

Exopolysaccharides from inhibit the growth of mycelia.

In the present study, the effect of exopolysaccharides (EPSs) extracted from on the growth of mycelia was determined. mycelia was cultivated with different concentrations of EPSs, and their mycelial growth rate, protein content, and enzyme activity were measured and compared. The results showed that EPSs inhibited the growth of .

Radiation-induced lymphopenia and the survival of women with cervical cancer: a meta-analysis.

The current systematic analysis and meta-analysis was aimed to evaluate the association between radiation-induced lymphopenia (RIL) and survival of women with cervical cancer (CC). PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant cohort studies comparing survival between women with CC who developed versus not developed RIL after radiotherapy. We pooled the results using a random-effects model that incorporates heterogeneity.

Omicsynin B4 potently blocks coronavirus infection by inhibiting host proteases cathepsin L and TMPRSS2.

The emergence of SARS-CoV-2 variants represents a major threat to public health and requires identification of novel therapeutic agents to address the unmet medical needs. Small molecules impeding viral entry through inhibition of spike protein priming proteases could have potent antiviral effects against SARS-CoV-2 infection. Omicsynin B4, a pseudo-tetrapeptides identified from Streptomyces sp.

The Application Value of Clinical Intervention Approaches Based on the Guidance of Knowledge, Belief, and Action Theory for Children with AB and the Analysis of Risk Factors for Poor Prognosis.

In order to explore the clinical efficacy of knowledge, information, and action theory combined with clinical nursing in children with asthmatic bronchitis (AB) and to analyze the influencing factors of poor prognosis, a total of 98 children with AB in our hospital from January 2021 to August 2022 are collected. The baseline data are analyzed and are randomly divided into a combination group ( = 49) and a single group ( = 49). The experimental results show that the baseline data of the research subjects are not comparable ( > 0.

Targeting 7-dehydrocholesterol reductase against EV-A71 replication by upregulating interferon response.

Recent studies have shown a close link between viral infections and cholesterol metabolism. Here, we reported that 7-dehydrocholesterol reductase (DHCR7), a terminal enzyme for catalyzing cholesterol synthesis in the Kandutsch-Russell pathway, is harnessed by enterovirus A71 (EV-A71) benefitting for its replication. Overexpression of DHCR7 resulted in upregulating of EV-A71 replication, while the S14A mutation, which reduces DHCR7 enzyme activity, has no effect on EV-A71 replication.

Optimization and SAR research at the benzoxazole and tetrazole rings of JNJ4796 as new anti-influenza A virus agents, part 2.

We have already reported the modification on the piperazine and phenyl rings of JNJ4796, a small-molecule fuse inhibitor targeting hemagglutinin (HA). In this study, we described the structure-activity relationship of the benzoxazole and tetrazole rings of JNJ4796. Many derivatives demonstrated good in vitro activity against IAV H1N1and Oseltamivir-resistant IAV H1N1 stains.

Effects and mechanism of Aβ on EV-A71 replication.

Background: β-Amyloid (Aβ) protein is a pivotal pathogenetic factor in Alzheimer's disease (AD). However, increasing evidence suggests that the brain has to continuously produce excessive Aβ to efficaciously prevent pathogenic micro-organism infections, which induces and accelerates the disease process of AD. Meanwhile, Aβ exhibits activity against herpes simplex virus type 1 (HSV-1) and influenza A virus (IAV) replication, but not against other neurotropic viruses.

Pediatric esophagogastroduodenoscopy in china: indications, diagnostic yield, and factors associated with findings.

Background: Large-scale data on esophagogastroduodenoscopy (EGD) in China are scarce. This study aimed to assess the indications and diagnostic yield of EGD in children and the relationship between factors (such as age, sex, and indications) and diagnostic yield.

Methods: We performed a prospective cross-sectional observational study involving patients aged < 18 years who underwent diagnostic EGD.

Role of pyroptosis in inflammation and cancer.

Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures, resulting in the release of cellular contents that can activate strong inflammatory and immune responses. Pyroptosis, an innate immune response, can be triggered by the activation of inflammasomes by various influencing factors. Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11, both of which cleave gasdermin D to release its N-terminal domain, which can bind membrane lipids and perforate the cell membrane.

RNF4 controls the extent of replication fork reversal to preserve genome stability.

Replication fork reversal occurs via a two-step process that entails reversal initiation and reversal extension. DNA topoisomerase IIalpha (TOP2A) facilitates extensive fork reversal, on one hand through resolving the topological stress generated by the initial reversal, on the other hand via its role in recruiting the SUMO-targeted DNA translocase PICH to stalled forks in a manner that is dependent on its SUMOylation by the SUMO E3 ligase ZATT. However, how TOP2A activities at stalled forks are precisely regulated remains poorly understood.

(-)-Lariciresinol Isolated from the Roots of Fortune ex Lindl. Inhibits Hepatitis B Virus by Regulating Viral Transcription.

Chronic hepatitis induced by hepatitis B virus (HBV) infection is a serious public health problem, leading to hepatic cirrhosis and liver cancer. Although the currently approved medications can reliably decrease the virus load and prevent the development of hepatic diseases, they fail to induce durable off-drug control of HBV replication in the majority of patients. The roots of Fortune ex Lindl.

Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and there is no specific drug to treat it. Recent results showed that 17-beta-hydroxysteroid dehydrogenase type 13 (HSD17B13) is associated with liver diseases, but these conclusions are controversial. Here, we showed that HSD17B13 was more highly expressed in the livers of NAFLD patients, and high expression was induced in the livers of murine NAFLD models and cultural hepatocytes treated using various etiologies.

Microbiota in Tumors: From Understanding to Application.

Microbes with complex functions have been found to be a potential component in tumor microenvironments. Due to their low biomass and other obstacles, intratumor microbiota is poorly understood. Mucosal sites and normal adjacent tissues are important sources of intratumor microbiota, while hematogenous spread also leads to the invasion of microbes.

Neddylation of Enterovirus 71 VP2 Protein Reduces Its Stability and Restricts Viral Replication.

Posttranslational modifications (PTMs) of viral proteins play critical roles in virus infection. The role of neddylation in enterovirus 71 (EV71) replication remains poorly defined. Here, we showed that the structural protein VP2 of EV71 can be modified by neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) in an E3 ligase X-linked inhibitor of apoptosis protein (XIAP)-dependent manner.