Pathogen-derived glyoxylate inhibits Tet2 DNA dioxygenase to facilitate bacterial persister formation.

Pathogenic bacterial persistence enables survival during antibiotic treatment, leading to treatment failure and recurrent infections, yet its underlying mechanisms remain unclear. Here, we reveal that glyoxylate, a metabolite originally evolved for alternative carbon utilization, functions as a signaling molecule to reprogram the host transcriptome and promote persister formation. Glyoxylate inhibits the DNA dioxygenase TET2, suppressing pro-inflammatory gene expression and attenuating host immune defense.

Mitochondrial NAD deficiency in vascular smooth muscle impairs collagen III turnover to trigger thoracic and abdominal aortic aneurysm.

Thoracic and abdominal aortic aneurysm poses a substantial mortality risk in adults, yet many of its underlying factors remain unidentified. Here, we identify mitochondrial nicotinamide adenine dinucleotide (NAD)⁺ deficiency as a causal factor for the development of aortic aneurysm. Multiomics analysis of 150 surgical aortic specimens indicated impaired NAD salvage and mitochondrial transport in human thoracic aortic aneurysm, with expression of the NAD transporter SLC25A51 inversely correlating with disease severity and postoperative progression.

Fungus Promotes CD8 T Cell-Mediated Anti-Tumor Immunity by Affecting Tumor-Associated Macrophages-Derived CCRL2.

Introduction: fungus (HSF)is an artificial substitute for and has shown promising therapeutic effects in various diseases including cancer. Previous studies have demonstrated that HSF can affect macrophage polarization and activate systemic immune response. In our preliminary experiments, we validated that HSF inhibited the proliferation of lung cancer (LC) cells, but the underlying mechanism is elusive.

Correcting mitochondrial loss mitigates NOTCH1-related aortopathy in mice.

Loss-of-function mutations in NOTCH1 were previously linked to thoracic aortopathy, a condition for which non-surgical treatment options are limited. Based on clinical proteome analysis, we hypothesized that mitochondrial fusion and biogenesis in aortic smooth muscle cells (SMCs) are crucial for regulating the progression of NOTCH1-related aortopathy. Here we demonstrate that SMC-specific Notch1 knockout mice develop aortic pathology, including stiffening, dilation and focal dissection.

Evolutionary Modes of wtf Meiotic Driver Genes in Schizosaccharomyces pombe.

Killer meiotic drivers are a class of selfish genetic elements that bias inheritance in their favor by destroying meiotic progeny that do not carry them. How killer meiotic drivers evolve is not well understood. In the fission yeast, Schizosaccharomyces pombe, the largest gene family, known as the wtf genes, is a killer meiotic driver family that causes intraspecific hybrid sterility.

Structure of the human TIP60 complex.

Mammalian TIP60 is a multi-functional enzyme with histone acetylation and histone dimer exchange activities. It plays roles in diverse cellular processes including transcription, DNA repair, cell cycle control, and embryonic development. Here we report the cryo-electron microscopy structures of the human TIP60 complex with the core subcomplex and TRRAP module refined to 3.

Structures of co-transcriptional RNA capping enzymes on paused transcription complex.

The 5'-end capping of nascent pre-mRNA represents the initial step in RNA processing, with evidence demonstrating that guanosine addition and 2'-O-ribose methylation occur in tandem with early steps of transcription by RNA polymerase II, especially at the pausing stage. Here, we determine the cryo-EM structures of the paused elongation complex in complex with RNGTT, as well as the paused elongation complex in complex with RNGTT and CMTR1. Our findings show the simultaneous presence of RNGTT and the NELF complex bound to RNA polymerase II.

The miR159a-DUO1 module regulates pollen development by modulating auxin biosynthesis and starch metabolism in citrus.

Achieving seedlessness in citrus varieties is one of the important objectives of citrus breeding. Male sterility associated with abnormal pollen development is an important factor in seedlessness. However, our understanding of the regulatory mechanism underlying the seedlessness phenotype in citrus is still limited.

Nuclear KRT19 is a transcriptional corepressor promoting histone deacetylation and liver tumorigenesis.

Background And Aims: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms.

Structural insights into histone exchange by human SRCAP complex.

Histone variant H2A.Z is found at promoters and regulates transcription. The ATP-dependent chromatin remodeler SRCAP complex (SRCAP-C) promotes the replacement of canonical histone H2A-H2B dimer with H2A.

Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients.

To investigate the relationship between the expression of hepatitis B virus (HBV) functional receptor sodium taurocholate cotransporting polypeptide (NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients. Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined.

Interplay between the transcription preinitiation complex and the +1 nucleosome.

Eukaryotic transcription starts with the assembly of a preinitiation complex (PIC) on core promoters. Flanking this region is the +1 nucleosome, the first nucleosome downstream of the core promoter. While this nucleosome is rich in epigenetic marks and plays a key role in transcription regulation, how the +1 nucleosome interacts with the transcription machinery has been a long-standing question.

Renewable-to-ammonia: Configuration strategy and technoeconomic analysis.

The increasing demand for chemical raw materials has provided opportunities for the ammonia (NH) industry. However, little attention has been devoted to the economic feasibility of renewable-to-ammonia (RE2A). Therefore, this paper proposes a technoeconomic model to research the optimal capacity configuration and quantify the levelized cost of ammonia (LCOA) for RE2A, which is a retrofitted plant based on coal-to-ammonia (C2A).

Structural visualization of transcription initiation in action.

Transcription initiation is a complex process, and its mechanism is incompletely understood. We determined the structures of de novo transcribing complexes TC2 to TC17 with RNA polymerase II halted on G-less promoters when nascent RNAs reach 2 to 17 nucleotides in length, respectively. Connecting these structures generated a movie and a working model.

Ascorbic Acid Reprograms Epigenome and Epitranscriptome by Reducing Fe(III) in the Catalytic Cycle of Dioxygenases.

Ascorbic acid (ASC) has been reported to stimulate DNA iterative oxidase ten-eleven translocation (TET) enzymes, Jumonji C-domain-containing histone demethylases, and potentially RNA mA demethylases FTO and ALKBH5 as a cofactor. Although ascorbic acid has been widely investigated in reprogramming DNA and histone methylation status , in cultured cells and mouse models, its specific role in the catalytic cycle of dioxygenases remains enigmatic. Here, we systematically investigated the stimulation of ASC toward TET2, ALKBH3, histone demethylases, and FTO.

Effect of vane angle on turbulence-chemistry interactions, temperature, flow field, burnout, and NOx emissions in swirling flames fueled by semicoke mixtures.

To enhance the combustion efficiency and reduce NOx emissions in large-scale semicoke and bituminous coal blends, an extensive numerical study was conducted. The focus of this study was to optimize the quaternary air vane angle (α) through detailed analysis of the temperature and flow fields, turbulence-chemistry interactions, char burnout, and NOx formation in a carefully scaled 1:5 dual-swirl burner. The results showed that with increasing α, the high-temperature flame region was narrowed and the peak temperature was reduced along with the broadened inner recirculation zone and the shrunken external recirculation zone due to better pulverized fuel-oxidant blending and reinforced convective heat transfer.

Perioperative outcomes of bi-pigtail catheter drainage strategy versus conventional chest tube after uniportal video-assisted thoracic lung surgery.

Objectives: Chest tube (CT) drainage is a main cause of postoperative pain in lung surgery. Here, we introduced a novel drainage strategy with bi-pigtail catheters (PCs) and conducted a randomized controlled trial to compare with conventional CT drainage after uniportal video-assisted thoracic surgery lung surgery.

Methods: A single-centre, prospective, open-labelled, randomized controlled trial (ChiCTR2000035337) was conducted with a preplanned sample size of 396.

A COF template-derived mesoporous CeO-supported Au nanoparticles catalyst for the oxidative esterification of benzaldehydes and benzyl alcohols.

The direct oxidative esterification of benzaldehydes and benzyl alcohols to high value-added aromatic esters under mild and green reaction conditions is significant in the fine chemical industry. The accurate design of catalysts with high catalytic performance is crucial for this process. Herein, 2,4,6-trimethylpyridine, benzoic anhydride, and terephthalaldehyde were used to prepare a covalent organic framework (COF) material, which was then used as a template to construct a mesoporous CeO-supported Au nanoparticles catalyst.

Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection.

Background: To examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection.

Methods: A total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients.

Metabolic disorders induced by PNPLA3 and TM6SF2 gene variants affect chronic kidney disease in patients infected with non-genotype 3 hepatitis C virus.

Background: Patients with chronic hepatitis C virus (HCV) infections differ in their risk for metabolic disorders and chronic kidney disease (CKD). The aim of this study was to investigate the effect of metabolic disorders induced by genetic factors on CKD in HCV-infected patients.

Methods: Patients with chronic non-genotype 3 HCV infection with or without CKD were examined.

Laser capture microdissection-based spatiotemporal transcriptomes uncover regulatory networks during seed abortion in seedless Ponkan (Citrus reticulata).

Seed abortion is an important process in the formation of seedless characteristics in citrus fruits. However, the molecular regulatory mechanism underlying citrus seed abortion is poorly understood. Laser capture microdissection-based RNA-seq combined with Pacbio-seq was used to profile seed development in the Ponkan cultivars 'Huagan No.