Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior T cells for cancer immunotherapy.

Cellular therapies are living drugs whose efficacy depends on persistence and survival. Expansion of therapeutic T cells employs hypermetabolic culture conditions to promote T cell expansion. We show that typical in vitro expansion conditions generate metabolically and functionally impaired T cells more reliant on aerobic glycolysis than those expanding in vivo.

Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut.

Akkermansia muciniphila is a promising target for managing obesity and type 2 diabetes (T2D), but human studies are limited. We conducted a 12-week randomized, double-blind, placebo-controlled trial involving 58 participants with overweight or obese T2D, who received A. muciniphila (AKK-WST01) or placebo, along with routine lifestyle guidance.

The atypical proteome of mitochondria from mature pollen grains.

To propagate their genetic material, flowering plants rely on the production of large amounts of pollen grains that are capable of germinating on a compatible stigma. Pollen germination and pollen tube growth are thought to be extremely energy-demanding processes. This raises the question of whether mitochondria from pollen grains are specifically tuned to support this developmental process.

Metabolomics in juvenile idiopathic arthritis: A distinct profile in patients under methotrexate.

The objective of the present study was to evaluate biochemical quantitative metabolites in peripheral blood serum samples of Juvenile Idiopathic Arthritis (JIA) patients and healthy controls. A cross-sectional study included 33 post-pubertal JIA (21 without and 12 with Methotrexate (MTX) women and 28 age-matched healthy controls. Metabolomic analyses based on targeted electrospray ionization tandem mass spectrometry were used to identify possible biochemical pathway modifications in serum from JIA patients.

Pulmonary rehabilitation under supervision of health-professional at institute versus conventional exercise-based pulmonary rehabilitation at home in COPD patients: A longitudinal cohort study.

Objectives: To evaluate the efficacy and safety of pulmonary rehabilitation under the supervision of health professionals at the institute versus conventional exercise-based pulmonary rehabilitation at home in Chronic Obstructive Pulmonary Disease (COPD) patients.

Methods: Patients of COPD received pulmonary rehabilitation under the supervision of a professional at the institute (PI cohort, n = 115) or self-driven traditional Chinese methods-based pulmonary rehabilitation at home (CE cohort, n = 127) or did not receive any type of pulmonary rehabilitation (ME cohort, n = 155). All patients received inhaled pharmacological treatment for COPD.

Research note: Detection of IGF2BP2 gene polymorphism associated with growth and reproduction traits of pigeon.

The Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) gene is closely associated with the diseases, fat deposition, and growth and reproduction traits in animals. Investigations into the relationship between the IGF2BP2 gene polymorphism and growth and reproduction traits provide valuable breeding information for enhancing productivity and economic gains in pigeon. In this study, the single nucleotide polymorphisms (SNPs) in 13 exons and the 3' untranslated region (3'UTR) of the IGF2BP2 gene in 292 female pigeons Tianxiang 1 strain were detected through Sanger sequencing, and their association with pigeons' growth and reproduction traits were explored.

On QSPR analysis of glaucoma drugs using machine learning with XGBoost and regression models.

Glaucoma is an irreversible, progressive, degenerative eye disorder arising because of increased intraocular pressure, resulting in eventual vision loss if untreated. The QSPR relates, mathematically, by employing various algorithms, a specified property of a molecule that arises either from physical, chemical, or biological phenomena using various aspects of its structure. Here in, a similar application based on topological indices and inferences derived from the structure for the calculation of different drug properties like molar refractivity, refractive index, enthalpy, boiling points, molecular weight, and polarizability is presented.

Fragment-Based Drug Discovery: Small Fragments, Big Impact - Success Stories of Approved Oncology Therapeutics.

Fragment-Based Drug Discovery (FBDD) has revolutionized drug discovery by overcoming the challenges of traditional methods like combinatorial chemistry and high-throughput screening (HTS). Leveraging small, low-molecular-weight fragments, FBDD achieves higher hit rates, reduced screening costs, and faster development timelines for clinically relevant drug candidates. This review explores FBDD's core principles, innovative methodologies, and its success in targeting diverse protein classes, including previously "undruggable" targets.

Mimicking the reactivity of drug metabolites: Biomolecule conjugation of an electrochemically-generated, reactive oxidation product of the antibiotic minocycline.

Minocycline is an antibiotic of the tetracycline family which is widely used to treat a range of medical conditions. Although it has been in use for more than 50 years, little information is available on its metabolism in the human body. In this study, we simulate the biotransformation of minocycline by means of electrochemistry coupled to mass spectrometry.

Enhanced bile acid detection and analysis in liver fibrosis with pseudo-targeted metabolomics.

Bile acids (BAs) are essential signaling molecules that engage in host and gut microbial metabolism, playing a crucial role in maintaining organismal stability. Liquid chromatography-mass spectrometry (LC-MS) is a widely employed technique for metabolite analysis in biological samples due to its high sensitivity, excellent specificity, and low detection limits. This method has emerged as the mainstream approach for the detection and analysis of BAs.

DNAzyme approach for simultaneous mRNA cap and poly(A) tail length analysis: A one-step method to multiple quality attributes.

The dynamic landscape of mRNA technology highlights the need for innovative quality control (QC) strategies. In this study, we described an efficient one-step digestion approach for concurrent generation of 5'- and 3'-end fragments, enabling simultaneous mRNA capping and poly(A) tail analysis. Tailored 10-23-type DNAzymes, designed from 5'- and 3'-Untranslated Regions (UTRs), selectively cleaved mRNA to release both the 5'-Capped or uncapped short fragments and 3'-Poly(A) tail cleavage products.

Rapid and accurate metabolite identification of traditional Chinese medicine based on UPLC-Q-TOF-MS coupled with UNIFI analysis platform and quantitative structure-retention relationship: Danshen-Honghua herbal pair as an example.

In recent years, metabolite identification of chemical constituents of traditional Chinese medicine (TCM) has been extensively studied. However, due to the intricacy of metabolic processes and the low concentration of metabolites, identifying metabolites of TCM in vivo is still a tough work. Meanwhile, credibility of metabolite identification through mass spectrum technology has been called into question by reason of the lack of metabolite standards.

Ligand guided in vivo crosslinking and affinity purification mass spectrometry for identifying membrane receptors of Tau.

Misfolded neurotoxic proteins, such as Tau protein, spread within the brain in many neurodegenerative diseases. Receptors play an important role in the recognition of spreading proteins for endocytosis. Blocking the receptors is essential to inhibit neurotoxic proteins spreading in the brain.

Construction of hierarchically porous covalent organic frameworks with enhanced enzyme accessibility for sensitive dopamine detection.

Immobilization of fragile enzymes is vital to expanding its application in the extracellular environment. Covalent organic frameworks (COFs), as a class of emerging porous materials, are promising platforms for enzyme immobilization owing to their high porosity and tunable structure. However, the interior pores of COFs often fail to play their roles because of inaccessibility, resulting in decreased performance of immobilized enzymes.

General design of self-supported Co-Ni/nitrogen-doped carbon nanotubes array for efficient oxygen evolution reaction.

The development of earth-abundant oxygen evolution reaction (OER) electrocatalysts with high activity and durability is critical for replacing noble-metal-based catalysts in the applications of scalable water electrolysis. A freestanding electrode architecture offers significant advantages over conventional coated powder forms due to enhanced kinetics and stability. However, precise control over electrode composition and the construction of uniformly distributed active sites within these electrodes remain challenging.

Synthetic phenolic antioxidant contamination in farmland soils induced by mulching films: Distribution and transformation pathways.

The occurrence and distribution of synthetic phenolic antioxidants (SPAs) originating from mulch film in farmland soils, along with their transformation characteristics and pathways, remain largely unknown. This study is the first to investigate nineteen SPAs and four transformation products (TPs) in farmland soils across China. In film-mulching soils, concentrations of SPAs (median, range: 83.

A novel Cu-coordinated fluorescent sensing system for specific detection of glyphosate and its applications in environmental and biological systems.

Glyphosate is a non-selective herbicide widely used in agriculture, and its overexposure poses significant health and environmental risks. Herein, a novel Cu-coordinated fluorescent sensing system (HYBC-Cu system) based on acylhydrazone groups was designed, capable of glyphosate-specific recognition. The HYBC-Cu system was constructed with simple steps, with the advantages of short recognition time (< 1 min), good specificity, anti-interference, and excellent sensitivity (LOD = 95 nM).

Long-term response mechanism of bacterial communities to chemical oxidation remediation in petroleum hydrocarbon contaminated groundwater.

The limited understanding of microbial response mechanism remains as a bottleneck to evaluate the long-term remediation effectiveness of in situ chemical oxidation in contaminated groundwater. In this study, we investigated long-term response of bacterial communities throughout five remediation stages of pre-oxidation, early-oxidation, late-oxidation, early-recovery and late-recovery. By analyzing bacterial biomass, taxa, diversity and metabolic functions, this work identified the consistently suppressed glyceraldehyde-3-phosphate dehydrogenase pathway and the enrichment of naphthalene degradation pathways for secondary products, suggesting persistent oxidation stress and enhanced microbial utilization of lower-molecular weight carbon sources at the oxidation and early-recovery stages.

Intercomparison of in-well, depth profile and online soil gas measurements for estimating petroleum natural source zone depletion rates: Will in-well gas samples suffice?

Natural Source Zone Deletion (NSZD) is a viable long-term management option for sites impacted by petroleum hydrocarbon fuels. NSZD rate estimation methods for petroleum mass losses often use soil gas gradients of oxygen, carbon dioxide, methane or vapour concentrations through the vadose zone. Seeking greater efficiencies, we investigated if existing short-screened wells are reliable for representative sampling of soil gases in a vadose zone undergoing NSZD.

Metabolic profiling of abdominal subcutaneous adipose tissue reveals effects of apple polyphenols for reversing high-fat diet induced obesity in C57BL/6 J mice.

Apple polyphenols (APP) can reduce obesity. However, the effects of APP on abdominal subcutaneous adipose tissue (aSAT) at metabolic level were unclear. In this study, 5-week APP intervenes were conducted on 10-week high-fat diet (HFD) feeding mice with doses of 200 and 500 mg/kg b.

First trimester cervical angles for the prediction of spontaneous preterm birth.

Objective: First trimester cervical angles for the prediction of spontaneous preterm birth (sPTB) remains unclear. The objective is to explore the potential value of first trimester cervical angles for the prediction of sPTB.

Study Design: This was a secondary analysis of data derived from a prospective cohort study for sPTB screening in singleton pregnancies at 11 + 0-13 + 6 weeks in women attending routine Down's syndrome screening at Prince of Wales Hospital, Hong Kong SAR, between June 2018 and July 2020.

Nitrite reverses nitroglycerin tolerance via repletion of a nitrodilator-activated nitric oxide store in vascular smooth muscle cells.

Repeated use of nitroglycerin results in a loss of its vasodilatory efficacy which limits its clinical use for the treatment of angina pectoris. This tolerance phenomenon is a defining characteristic of all compounds classified as nitrodilators, which includes NTG as well as S-nitrosothiols and dinitrosyl iron complexes. These compounds vasodilate via activation of soluble guanylate cyclase, although they do not release requisite amounts of free nitric oxide (NO) and some do not even cross the plasma membrane.

Potential for application of direct thrombin inhibitors isolated from Euphorbia resinifera O.Berg latex in fibrin clot formation.

Direct thrombin inhibitors (designated as EuRL-DTIs) were partially purified from ethanol extracts of Euphorbia resinifera O.Berg latex. The obtained EuRL-DTIs comprised four major compounds: two isomers of phenolic compounds (CHO) and two amide compounds (tentatively identified as CHNO and CHNO), as identified by liquid chromatography and electrospray ionisation quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, and/or nuclear magnetic resonance (NMR) spectroscopy.

Traditional Chinese medicine Chaiqinchengqi decoction for patients with acute pancreatitis: A randomized clinical trial.

Background: Chaiqinchengqi decoction, a traditional Chinese medicine, has shown promising effects in in vitro, animal and preliminary small human studies for acute pancreatitis, but evidence of clinical practice is limited.

Purpose: To investigate whether Chaiqinchengqi decoction could improve clinical outcomes in patients with acute pancreatitis.

Study Design: Prospective, pragmatic, randomized controlled trial.

miR378a-3p in serum extracellular vesicles is associated with pancreatic beta-cell mass in diabetic states.

The condition in which the insulin secretory ability of pancreatic β-cells decreases in diabetes is extremely important, but there are currently no biomarkers that reflect pancreatic β-cell failure. Therefore, we conducted a search for biomarkers, using pancreatic β-cell-specific 3-Phosphoinositide-dependent protein kinase 1 (PDK1) knockout mice, which develop severe hyperglycemia due to a decrease in pancreatic β-cell mass without insulin resistance. The analysis was performed in young mice when metabolic abnormalities were not yet apparent.