Protective Efficacy of Subunit Vaccine Expressing Rv0976c Against Tuberculosis.

Objectives: The construction of subunit vaccines based on antigens that can induce strong cellular immunity is a widely accepted strategy to develop new tuberculosis vaccines. This study screens immunogens with potential for subunit vaccine development from seven candidate antigens and then verifies their vaccine efficacy.

Design: C57BL/6 mice were immunized subcutaneously with purified PPE19, PPE50, FadD21, Rv1505c, Rv1506c, Rv2035, and Rv0976c proteins formulated with Freund's adjuvant to evaluate both the antigen-specific Th1 cellular immune responses and IgG level.

Computational nanobody design through deep generative modeling and epitope landscape profiling.

Nanobodies, one-tenth the size of conventional antibodies, have gained attention as therapeutic agents for autoimmune diseases, cancer, and viral infections. However, traditional methods for nanobody discovery are often time-consuming and labor-intensive. In this study, we present a computational design framework that integrates deep generative modeling with epitope profiling.

BAY11-7082 Targets RNF25 to Reverse TRIP4 Ubiquitination-dependent NF-κB Activation and Apoptosis Resistance in Renal Cell Carcinoma.

NF-κB pathway dysregulation, a common driver of therapy resistance in cancer, promotes survival by suppressing apoptosis. While the anti-apoptotic role of NF-κB is recognized, the molecular mechanisms underlying this process remain poorly defined. Here, we identify the E3 ubiquitin ligase RNF25 as a key mediator of NF-κB-dependent apoptosis resistance in renal cell carcinoma cells, enabling evasion of multiple targeted therapies.

Targeting the WSB2-NOXA axis in cancer cells for enhanced sensitivity to BCL-2 family protein inhibitors.

Anti-apoptotic B-cell lymphoma-2 (BCL-2) family proteins are frequently overexpressed in various cancers, playing a pivotal role in cancer initiation and progression, as well as intrinsic or acquired resistance to therapy. Although inhibitors targeting BCL-2, such as Venetoclax, have shown efficacy in hematological malignancies, their therapeutic potential in solid tumors remains limited. Identifying novel molecular targets to overcome resistance to these inhibitors is of significant clinical importance.

Cancer-associated SPOP mutations enlarge nuclear size and facilitate nuclear envelope rupture upon farnesyltransferase inhibitor treatment.

Nuclear size is crucial for cellular functions and often increases with malignancy. Irregular nuclei are linked to aggressive tumors, driven by genetic and epigenetic changes. However, the precise mechanisms controlling nuclear size are still not fully understood.

Molecular Insight Into the Hydrolysis of Phthalate Esters by a Family IV Esterase.

Phthalate esters (PAEs) are prevalent environmental contaminants, with their biodegradation efficiently driven by microorganisms through ester bond hydrolysis. This study investigates the mechanism of Poc14, a novel family IV esterase, using x-ray crystallography, bioinformatics, biochemistry and site-directed mutagenesis. Phylogenetic analysis classifies Poc14 as a family IV esterase with conserved catalytic motifs crucial for its activity.

Mitochondrial dysfunction in the regulation of aging and aging-related diseases.

Aging is an irreversible physiological process that progresses with age, leading to structural disorders and dysfunctions of organs, thereby increasing the risk of chronic diseases such as neurodegenerative diseases, diabetes, hypertension, and cancer. Both organismal and cellular aging are accompanied by the accumulation of damaged organelles and macromolecules, which not only disrupt the metabolic homeostasis of the organism but also trigger the immune response required for physiological repair. Therefore, metabolic remodeling or chronic inflammation induced by damaged tissues, cells, or biomolecules is considered a critical biological factor in the organismal aging process.

Structural and functional insights into β-glucosidase derived from Thermoproteus sp. AZ2.

β-glucosidase (BGL) is a pivotal enzyme with broad implications across diverse industrial sectors, demonstrating robust proficiency in catalyzing glycosidic bond hydrolysis, particularly critical in lignocellulosic biomass conversion. This study explored the structural features and enzymatic activity of Thermoproteus sp. AZ2-derived BGL (TsBGL2).

Protocol for purification, crystallization, and structure determination of the mpox virus mRNA cap N7 methyltransferase complex.

The mpox virus (MPXV) mRNA cap N7 methyltransferase (RNMT) methylates guanosine at mRNA 5'-cap N7 positions to enable immune evasion. Here, we present a protocol for E1-E12 complex purification and crystallization. We describe steps for rational sequence design of the complex, co-expression in E.

A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.

Despite the manifestation and contribution of cellular senescence to aging and various diseases, accurate identification of heterogeneous senescent cells remains challenging. Current senescence evaluation methods rely mainly on limited markers or homogeneous samples, which might fail to capture universal senescence features, limiting their generalizability. Here we developed the human universal senescence index (hUSI), an accurate and robust senescence evaluation method for diverse cells and samples.

DNA Subunit Vaccine and Recombinant BCG Based on Mycobacterial Lipoprotein LprO Enhance Anti-Tuberculosis Protection in the Lungs of Mice.

: Over the past two centuries, tuberculosis (TB) has been responsible for approximately one billion deaths and continues to represent a significant global health challenge. Despite extensive research efforts, fully effective strategies for the prevention or eradication of TB remain elusive, highlighting the urgent demand for novel vaccines with enhanced safety profiles and efficacy. Lipoproteins, integral surface proteins of mycobacteria, are frequently associated with virulence and display notable immunogenicity, rendering them promising candidates for vaccine development.

Enhancing recombinant protein production through Cre-loxP mediated chromosomal rearrangement evolution in Kluyveromyces marxianus.

Chromosomal rearrangements can drive adaptive evolution; however, whether the rearrangements in non-coding and non-promoter regions can lead to new phenotypes under selective pressures remains unclear. Additionally, highly producing recombinant proteins is a key industrial task but poses stress on host cells. Therefore, it is desirable to investigate the role of chromosomal rearrangement in non-coding and non-promoter regions during high-yield recombinant protein phenotype formation.

Enhancing the Protein Stability of an Anticancer VHH-Fc Heavy Chain Antibody through Computational Modeling and Variant Design.

VHHs (also known as nanobodies) are important therapeutic antibodies. To prolong their half-life in bloodstream, VHHs are usually fused to the Fc fragment of full-length antibodies. However, stability is often the main challenge for their commercialization, and methods to improve stability are still lacking.

IDO1 inhibitors block septic cytokine storm by suppressing the IDO1-AHR-CYP1A1 axis.

Indoleamine-2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in tryptophan (Trp) catabolism along kynurenine (Kyn) pathway. Increased IDO1 activity has been noticed in patients with sepsis, while IDO1's involvement in sepsis, especially in the initial cytokine storm phase is not yet completely understood. Using the GEO database and clinical samples of sepsis, current study revealed that IDO1-AHR-CYP1A1 axis was significantly upregulated and closely related to cytokine storm in septic patients.

IDO1-mediated AhR activation up-regulates pentose phosphate pathway via NRF2 to inhibit ferroptosis in lung cancer.

Ferroptosis is a type of cell death marked by iron-dependent lipid peroxide accumulation. Indoleamine 2,3-dioxygenase 1 (IDO1), a key enzyme in the catabolism of tryptophan through kynurenine pathway, participates in the development of multiple tumor types. However, the role of IDO1 in tumor ferroptosis is unclear.

Culturable Human Microorganisms and the Impact of Transportation Conditions on Cultivability.

The composition of the human microbiome is a critical health indicator, and culture-independent methodologies have substantially advanced our understanding of human-associated microorganisms. However, precise identification and characterization of microbial strains require culture-based techniques. Recently, the resurgence of culturomics, combined with high-throughput sequencing technology, has reduced the high labor demand of pure culture methods, facilitating a more efficient and comprehensive acquisition of culturable microbial strains.

Alien Chromosome Serves as a Novel Platform for Multiple Gene Expression in .

is an emerging yeast cell host for diverse products, but multiple-gene expression in faces challenges due to limited current knowledge of -regulatory elements and insertion loci. Our previous study transferred an alien chromosome I (R1) into , resulting in the creation of the monochromosomal hybrid yeast KS-R1. All R1 genes were actively transcribed, providing a series of loci with varying transcriptional activities.

Characterisation of bla-bearing IncHI2 plasmid from Escherichia fergusonii in China.

Objective: Carbapenems are considered to be the last resort for serious infections caused by multidrug-resistant Gram-negative bacteria, and the emergence of carbapenem-resistant Enterobacteriaceae has posed a serious threat to human health. However, carbapenem resistance is rarely reported in Escherichia fergusonii. In this study, a New Delhi metallo-β-lactamase (NDM)-5-producing E.

3' untranslated region somatic variants connect alternative polyadenylation dysregulation in human cancers.

Somatic variants in the cancer genome influence gene expression through diverse mechanisms depending on their specific locations. However, a systematic evaluation of the effects of somatic variants located in 3' untranslated regions (3' UTRs) on alternative polyadenylation (APA) of mRNA remains lacking. In this study, we analyze 10,199 tumor samples across 32 cancer types and identify 1333 somatic single nucleotide variants (SNVs) associated with abnormal 3' UTR APA.

Metabolic engineering of Kluyveromyces marxianus to produce myo-inositol from starch.

To efficiently produce myo-inositol from glucose, the PGI1, ZWF1, ITR2, and MIOX5 genes in Kluyveromyces marxianus were knocked out to block glucose metabolism via the Embden-Meyerhof-Parnas (EMP) and pentose phosphate pathways (PPP), prevent myo-inositol oxidative degradation. The metabolically engineered KM-JC4 strain, introduced with myo-inositol synthesis genes, produced 80.7 g/L in a 5 L bioreactor using glucose and glycerol as carbon sources.

Deficiency of Gut-Enriched Lipase H Promotes Gut Aging and Reduces Lifespan in .

Unlabelled: , a gut-enriched Lipase H encoding gene, shows decreased expression during gut aging in both fruit fly and mouse. However, whether such evolutionary conserved plays a protective role in gut aging remains unknown. Here we report that knocking down , the ortholog of the mammalian , led to a shortened lifespan.

Single-cell RNA-seq reveals the immune response of Co-infection with streptococcus pneumoniae after influenza A virus by a lung-on-chip: The molecular structure and mechanism of tight junction protein ZO-1.

Secondary bacterial infection is the main cause of pneumonia after influenza virus infection. This study aims to explore the impact of co-infection of influenza A virus (IAV) and Streptococcus pneumoniae (SP) on lung immune response using a human lung-on-chip model and single-cell RNA sequencing technology, with a focus on the molecular structure and mechanism of action of the tight junction protein ZO-1 in this process. Research and construct a human lung-on-chip model to simulate the microenvironment of the lungs in vivo.

Characterization and optimization of mnn11Δ-mediated enhancement in heterologous protein production in Kluyveromyces marxianus.

Background: N-glycosylation is a prevalent post-translational modification in eukaryotes, essential for regulating protein secretion. In Saccharomyces cerevisiae, glycosylation mutants have been shown to enhance the secretion of heterologous glycosylated proteins. However, whether these mutants can also increase the secretion of non-glycosylated proteins and whether the growth defects associated with glycosylation mutations can be mitigated remains unclear.