Co-Expression of Dominant-Negative TGF-β Receptor 2 Enhances the Therapeutic Efficacy of Novel TREM1/DAP12-BB-Based CAR-T Cells in Solid Tumours.

Chimeric antigen receptor (CAR) T-cell therapy has exhibited remarkable efficacy in the treatment of haematological malignancies, yet its application in solid tumours is hindered by the immunosuppressive tumour microenvironment (TME). In this study, a novel SS1-TREM1/DAP12-BB CAR-T cell was devised to target ovarian cancer and further engineered to co-express the dominant-negative TGF-β receptor 2 (DNR) to combat CAR-T cell exhaustion in TME. The incorporation of DNR effectively blocked TGF-β signalling, thereby enhancing CAR-T cell survival and antitumor activity in a TGF-β1-rich environment.

Genetic improvement of low-lignin poplars: a new strategy based on molecular recognition, chemical reactions and empirical breeding.

As an important source of pollution in the papermaking process, the presence of lignin in poplar can seriously affect the quality and process of pulping. During lignin synthesis, Caffeoyl-CoA-O methyltransferase (CCoAOMT), as a specialized catalytic transferase, can effectively regulate the methylation of caffeoyl-coenzyme A (CCoA) to feruloyl-coenzyme A. Targeting CCoAOMT, this study investigated the substrate recognition mechanism and the possible reaction mechanism, the key residues of lignin binding were mutated and the lignin content was validated by deep convolutional neural-network model based on genome-wide prediction (DCNGP).

Species- and organ-specific contribution of peroxisomal cinnamate:CoA ligases to benzoic and salicylic acid biosynthesis.

Salicylic acid (SA) is a prominent defense hormone whose basal level, organ-specific accumulation, and physiological role vary widely among plant species. Of the 2 known pathways of plant SA biosynthesis, the phenylalanine ammonia lyase (PAL) pathway is more ancient and universal but its biosynthetic and physiological roles in diverse plant species remain unclear. Studies in which the PAL pathway is specifically or completely inhibited, as well as a direct comparison of diverse species and different organs within the same species, are needed.

Identification of core therapeutic targets for Monkeypox virus and repurposing potential of drugs: A WEB prediction approach.

A new round of monkeypox virus has emerged in the United Kingdom since July 2022 and rapidly swept the world. Currently, despite numerous research groups are studying this virus and seeking effective treatments, the information on the open reading frame, inhibitors, and potential targets of monkeypox has not been updated in time, and the comprehension of monkeypox target ligand interactions remains a key challenge. Here, we first summarized and improved the open reading frame information of monkeypox, constructed the monkeypox inhibitor library and potential targets library by database research as well as literature search, combined with advanced protein modeling technologies (Sequence-based and AI algorithms-based homology modeling).

Elucidating the gastroprotective mechanisms of Imperata cylindrica Beauv.var. major (Nees) C.E.Hubb through UHPLC-MS/MS and systems network pharmacology.

Imperata cylindrica Beauv.var. major (Nees) C.

PDGFRB promotes dedifferentiation and pulmonary metastasis through rearrangement of cytoskeleton under hypoxic microenvironment in osteosarcoma.

Background: Osteosarcoma (OS) cells commonly suffer from hypoxia and dedifferentiation, resulting in poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated cellular signaling.

Methods: We performed sphere formation assays and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers.

Structural insights into the mechanotransducing mechanism of FtsEX in cell division.

The filamentous temperature-sensitive (Fts) protein FtsEX plays a pivotal role in () cell division by facilitating the activation of peptidoglycan hydrolysis through the adaptor EnvC. FtsEX belongs to the type VII ATP-binding cassette (ABC) transporter superfamily, which harnesses ATP energy to induce mechanical force, triggering a cascade of conformational changes that activate the pathway. However, the precise mechanism by which FtsEX initiates mechanotransmission remains elusive.

Targeting non-coding RNAs to overcome osimertinib resistance in -mutated non-small cell lung cancer.

Osimertinib, a third-generation inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, exhibits remarkable efficacy in prolonging the survival of patients with non-small cell lung cancer (NSCLC) carrying mutations, surpassing the efficacy of first- and second-generation EGFR tyrosine kinases. Nevertheless, the emergence of osimertinib resistance is inevitable, necessitating an investigation into the underlying mechanisms. Increasing evidence has revealed that non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, play a significant role in the development and progression of lung cancer.

Discovery of a Potent, Orally Active, and Long-Lasting P2X7 Receptor Antagonist as a Preclinical Candidate for Delaying the Progression of Chronic Kidney Disease.

Chronic kidney disease (CKD) is a condition characterized by functional deterioration with sustained inflammation and progressive fibrosis of the kidneys affecting over 800 million people worldwide. The P2X7 receptor (P2X7R) plays a key role in CKD progression. Our previous P2X7R antagonists demonstrated good efficacy for treating kidney injury but were limited by low oral exposure and short half-life, restricting their application.

Ultra-processed foods consumption and risk of age-related eye diseases: a prospective cohort study with UK biobank.

Purpose: Consumption of ultra-processed foods (UPF) has been associated with increased risks of various age-related diseases. However, the potential association between UPF consumption and age-related eye diseases (AREDs) remains unclear. We aim to assess the associations between consumption of UPF and risk of AREDs including age-related macular degeneration (AMD), cataract and glaucoma.

Impact of acute heat stress on mitochondrial function, ultrastructure and cardiolipin distribution in .

Besides providing energy to sustain life, mitochondria also play crucial roles in stress response and programmed cell death. The mitochondrial hallmark lipid, cardiolipin (CL), is essential to the maintenance of mitochondrial structure and function. However, how mitochondria and CL are involved in stress response is not as well defined in plants as in animal and yeast cells.

Feasibility of the inhibitor development for cancer: A systematic approach for drug design.

The traditional Chinese medicine (TCM) bupleurum-ginger-licorice formula presents significant anti-cancer effects, but its active ingredients and inhibitory mechanism remain unclear. In this work, the core effective ingredient quercetin and its signal transducer and activator of transcription 3 (Stat3) receptor both were identified by network pharmacology. Quercetin is a low-toxicity, non-carcinogenic flavonoid with antioxidant, anti-inflammatory and anticancer activities, which is widely distributed in edible plants.

Revealing the graded activation mechanism of neurotensin receptor 1.

Graded activation contributes to the precise regulation of GPCR activity, presenting new opportunities for drug design. In this work, a total of 10 μs enhanced-sampling simulations are performed to provide molecular insights into the binding dynamics differences of the neurotensin receptor 1 (NTSR1) to the full agonist SRI-9829, partial agonist RTI-3a and inverse agonist SR48692. The possible graded activation mechanism of NTSR1 is revealed by an integrated analysis utilizing the reweighted potential of mean force (PMF), deep learning (DL) and transfer entropy (TE).

Pt(IV) Prodrug Photoactivation: A Promising Strategy for Cancer Therapy.

Platinum (II) drugs, including cisplatin, carboplatin, and oxaliplatin, have achieved significant clinical success in cancer treatment. However, their clinical application has been greatly hindered by various adverse factors, such as non-specific activation and drug resistance. Compared with Pt(II) drugs, the axial ligands within Pt(IV) compounds can improve the pharmacokinetic properties, selectivity, and biological activity, implementing alternative cytotoxic mechanisms beyond DNA cross-linking and partially overcoming drug resistance.

Identification of Auxiliary Organellar Targeting Signals for Plant Peroxisomes Using Bioinformatic Analysis of Large Protein Sequence Datasets Followed by Experimental Validation.

Eukaryotic cells are compartmentalized by membrane-bounded organelles to ensure that specific biochemical reactions and cellular functions occur in a spatially restricted manner. The subcellular localization of proteins is largely determined by their intrinsic targeting signals, which are mainly constituted by short peptides. A complete organelle targeting signal may contain a core signal (CoreS) as well as auxiliary signals (AuxiS).

Impacts of travel duration on urban-rural resident free vaccination behavior: Chinese COVID-19 vaccine booster dose evidence.

This study aimed to evaluate how the duration of travel affects the behavior of urban and rural residents regarding free COVID-19 vaccination, and provide scientific evidence for promoting free vaccination and building an immune barrier to cope with future epidemics. From August 3, 2022 to February,18,2023, A follow-up survey was conducted in urban and rural adults in four cities in China to collect information on socio-demographic factors, vaccination status and travel time for vaccination. Propensity score matching (PSM) analysis was deployed to measure the net difference of the enhanced vaccination rate between urban and rural residents in different traffic time distribution.

Enhancing genome-wide populus trait prediction through deep convolutional neural networks.

As a promising model, genome-based plant breeding has greatly promoted the improvement of agronomic traits. Traditional methods typically adopt linear regression models with clear assumptions, neither obtaining the linkage between phenotype and genotype nor providing good ideas for modification. Nonlinear models are well characterized in capturing complex nonadditive effects, filling this gap under traditional methods.

Efficacy of Polyethylene Glycol Electrolyte Powder Combined With Linaclotide for Colon Cleansing in Patients With Chronic Constipation Undergoing Colonoscopy: A Multicenter, Single-Blinded, Randomized Controlled Trial.

Introduction: Constipation is an independent risk factor for poor bowel preparation. This study aimed to evaluate the bowel cleansing efficacy and safety of polyethylene glycol (PEG) combined with linaclotide (lin) for colonoscopy in patients with chronic constipation (CC).

Methods: This single-blinded, randomized, controlled, and multicenter study was conducted from July 2021 to December 2022 at 7 hospitals.

Relationship between brain white matter damage and grey matter atrophy in hereditary spastic paraplegia types 4 and 5.

Background And Purpose: White matter (WM) damage is the main target of hereditary spastic paraplegia (HSP), but mounting evidence indicates that genotype-specific grey matter (GM) damage is not uncommon. Our aim was to identify and compare brain GM and WM damage patterns in HSP subtypes and investigate how gene expression contributes to these patterns, and explore the relationship between GM and WM damage.

Methods: In this prospective single-centre cohort study from 2019 to 2022, HSP patients and controls underwent magnetic resonance imaging evaluations.