MBD2 promotes epithelial-to-mesenchymal transition (EMT) and ARDS-related pulmonary fibrosis by modulating FZD2.

Objective: To investigate the role and underlying mechanism of Methyl-CpG binding domain protein 2 (MBD2) in the pathogenesis of acute respiratory distress syndrome (ARDS)-related pulmonary fibrosis.

Methods: Murine models for ARDS-related pulmonary fibrosis were established in wildtype or MBD2 knockout mice, expressions of MBD2 were determined with immunohistochemistry (IHC), immunofluorescence, and western blot. Epithelial-to-mesenchymal transition (EMT) was detected with determined with decreased expression of E-cadherin and increased expressions of N-cadherin, Vimentin, and α-smooth muscle actin (α-SMA).

Time-varying ambient air pollution exposure is associated with gut microbiome variation in the first 2 years of life.

The infant gut microbiome matures greatly in the first year of life. Ambient air pollution (AAP) exposure is associated with the infant gut microbiome. However, whether time-varying AAP influences infant gut microbiome variation is rarely investigated.

Bioinformatics analysis of an immunotherapy responsiveness-related gene signature in predicting lung adenocarcinoma prognosis.

Background: Immune therapy has become first-line treatment option for patients with lung cancer, but some patients respond poorly to immune therapy, especially among patients with lung adenocarcinoma (LUAD). Novel tools are needed to screen potential responders to immune therapy in LUAD patients, to better predict the prognosis and guide clinical decision-making. Although many efforts have been made to predict the responsiveness of LUAD patients, the results were limited.

Multiple Cofactor Engineering Strategies to Enhance Pyridoxine Production in .

Pyridoxine, also known as vitamin B, is an essential cofactor in numerous cellular processes. Its importance in various applications has led to a growing interest in optimizing its production through microbial biosynthesis. However, an imbalance in the net production of NADH disrupts intracellular cofactor levels, thereby limiting the efficient synthesis of pyridoxine.

Enhancement of vitamin B production driven by omics analysis combined with fermentation optimization.

Background: Microbial engineering aims to enhance the ability of bacteria to produce valuable products, including vitamin B for various applications. Numerous microorganisms naturally produce vitamin B, yet the metabolic pathways involved are rigorously controlled. This regulation by the accumulation of vitamin B poses a challenge in constructing an efficient cell factory.

Engineering and finetuning expression of SerC for balanced metabolic flux in vitamin B production.

Vitamin B plays a crucial role in cellular metabolism and stress response, making it an essential component for growth in all known organisms. However, achieving efficient biosynthesis of vitamin B faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production. In this study, our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase (SerC) to resolve its redundancy and promiscuity.

Inhibition of METTL3 alleviated LPS-induced alveolar epithelial cell apoptosis and acute lung injury via restoring neprilysin expression.

Aims: To investigate the role and mechanisms of methyltransferase-like 3 (METTL3) in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI).

Main Methods: LPS intratracheally instillation was applied in alveolar epithelial cell METTL3 conditional knockout (METTL3-CKO) mice and their wild-type littermates. In addition, METTL3 inhibitor STM2457 was used.

Protein engineering and iterative multimodule optimization for vitamin B production in Escherichia coli.

Vitamin B is an essential nutrient with extensive applications in the medicine, food, animal feed, and cosmetics industries. Pyridoxine (PN), the most common commercial form of vitamin B, is currently chemically synthesized using expensive and toxic chemicals. However, the low catalytic efficiencies of natural enzymes and the tight regulation of the metabolic pathway have hindered PN production by the microbial fermentation process.

New ε-N-thioglutaryl-lysine derivatives as SIRT5 inhibitors: Chemical synthesis, kinetic and crystallographic studies.

SIRT5 has been implicated in various physiological processes and human diseases, including cancer. Development of new highly potent, selective SIRT5 inhibitors is still needed to investigate disease-related mechanisms and therapeutic potentials. We here report new ε-N-thioglutaryllysine derivatives, which were designed according to SIRT5-catalysed deacylation reactions.

Microbial Cell Factories for Green Production of Vitamins.

Vitamins are a group of essential nutrients that are necessary to maintain normal metabolic activities and optimal health. There are wide applications of different vitamins in food, cosmetics, feed, medicine, and other areas. The increase in the global demand for vitamins has inspired great interest in novel production strategies.

[Advances in metabolic engineering for vitamins production].

Vitamins are organic substances that are essential for the maintenance of life activities. Generally, vitamins need to be obtained from the diet or from some synthetic source as the body cannot synthesize vitamins, or the amounts of the synthesized vitamins are insufficient. At present, vitamins are widely used in medicine, food additives, feed additives, cosmetics and other fields, and the global demand for vitamins is constantly growing.

New aspects of microbial vitamin K2 production by expanding the product spectrum.

Vitamin K2 (menaquinone, MK) is an essential lipid-soluble vitamin with critical roles in blood coagulation and bone metabolism. Chemically, the term vitamin K2 encompasses a group of small molecules that contain a common naphthoquinone head group and a polyisoprenyl side chain of variable length. Among them, menaquinone-7 (MK-7) is the most potent form.

Comprehensive Analysis of the Prognosis and Correlations With Immune Infiltration of S100 Protein Family Members in Hepatocellular Carcinoma.

S100 protein family members (S100s) are commonly dysregulated in various tumors including hepatocellular carcinoma (HCC). However, the diverse expression, mutation, prognosis and associations with immune infiltration of S100s in HCC have yet to be analyzed. Herein we investigated the roles of S100s in HCC from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas, Kaplan-Meier Plotter, cBioPortal and TIMER databases.

A cyclin protein governs the infectious and sexual life cycles of Cryptococcus neoformans.

Cell cycle is a fundamental process underlying growth and development in evolutionarily diverse organisms, including fungi. In human fungal pathogens, cell cycle control generally determines their life cycles, either in the environment or during infections. Thus, cell cycle components can potentially serve as important targets for the development of antifungal strategy against fungal infections.

Engineering to improve tryptophan production via genetic manipulation of precursor and cofactor pathways.

Optimizing the supply of biosynthetic precursors and cofactors is usually an effective metabolic strategy to improve the production of target compounds. Here, the combination of optimizing precursor synthesis and balancing cofactor metabolism was adopted to improve tryptophan production in . First, glutamine synthesis was improved by expressing heterologous glutamine synthetase from and in the engineered strain KW001, resulting in the best candidate strain TS-1.

Genetic basis for coordination of meiosis and sexual structure maturation in .

In the human fungal pathogen , sex can benefit its pathogenicity through production of meiospores, which are believed to offer both physical and meiosis-created lineage advantages for its infections. sporulation occurs following two parallel events, meiosis and differentiation of the basidium, the characteristic sexual structure of the basidiomycetes. However, the circuit integrating these events to ensure subsequent sporulation is unclear.

Measurements of the gravitational constant using two independent methods.

The Newtonian gravitational constant, G, is one of the most fundamental constants of nature, but we still do not have an accurate value for it. Despite two centuries of experimental effort, the value of G remains the least precisely known of the fundamental constants. A discrepancy of up to 0.

MADS-Box Transcription Factor Regulates Dimorphic Transition, Conidiation, and Germination of .

The opportunistic human pathogen exhibits a temperature-dependent dimorphic transition, which is closely related with its pathogenicity. This species grows as multinucleate mycelia that produce infectious conidia at 25°C, while undergoes a dimorphic transition to generate uninucleate yeast form cells at 37°C. The mechanisms of phenotype switching are not fully understood.

Efficacy and safety of trastuzumab emtansine (T-DM1) in the treatment of HER2-positive metastatic breast cancer (MBC): a meta-analysis of randomized controlled trial.

Aims: Trastuzumab emtansine (T-DM1), an antibody-drug conjugate against human epidermal growth factor receptor 2 (HER2), has been used in the treatment of patients with HER2-positive metastatic breast cancer (MBC). We conducted a meta-analysis to evaluate the efficacy and toxicity of T-DM1 for the treatment of patients with HER2-positive MBC.

Materials And Methods: Randomized controlled trials (RCTs), published in Pubmed, Embase, and Web of Science were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with MBC who were treated with T-DM1.

Assessing nursing quality in paediatric intensive care units: a cross-sectional study in China.

Background: Nursing-sensitive indicators are considered effective tools for improving the quality of care in hospitals. However, these have not been used in paediatric intensive care units (PICUs) in China.

Aim: To develop nursing-sensitive indicators for PICUs and to assess the quality of nursing in PICUs in China based on the nursing-sensitive indicators.

Structure and biosynthesis of fumosorinone, a new protein tyrosine phosphatase 1B inhibitor firstly isolated from the entomogenous fungus Isaria fumosorosea.

Fumosorinone, isolated from the entomogenous fungus Isaria fumosorosea, is a new 2-pyridone alkaloid which is elucidated by HRESIMS 1D and 2DNMR. Fumosorinone is structurally similar to tenellin and desmethylbassianin but it differs in chain length and degree of methylation. It is characterized by a classic noncompetitive inhibitor of protein tyrosine phosphatase 1B (IC50 14.

Three new pigment protein tyrosine phosphatases inhibitors from the insect parasite fungus Cordyceps gracilioides: terreusinone A, pinophilin C and cryptosporioptide A.

Three new pigment compounds--terreusinone A (1), pinophilin C (2) and cryptosporioptide A (3)-were isolated from a solid culture of Cordyceps gracilioides. The structures of these compounds were determined by extensive spectroscopic analysis including HRESIMS, 1D- and 2D-NMR. The structure of terreusinone A (1) was further confirmed by single-crystal X-ray crystallographic diffraction analysis.

Determination of the Newtonian gravitational constant G with time-of-swing method.

We present a new value of the Newtonian gravitational constant G by using the time-of-swing method. Several improvements greatly reduce the uncertainties: (1) measuring the anelasticity of the fiber directly; (2) using spherical source masses minimizes the effects of density inhomogeneity and eccentricities; (3) using a quartz block pendulum simplifies its vibration modes and minimizes the uncertainty of inertial moment; (4) setting the pendulum and source masses both in a vacuum chamber reduces the error of measuring the relative positions. By two individual experiments, we obtain G = 6.