A physiologically-based quantitative systems pharmacology model for mechanistic understanding of the response to alogliptin and its application in patients with renal impairment.

Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In this study, we developed a comprehensive physiologically-based quantitative systematic pharmacology model of the alogliptin-glucose control system to predict plasma exposure and use glucose as a clinical endpoint to prospectively understand its therapeutic outcomes with varying renal function. Our model incorporates a PBPK model for alogliptin, DPP-4 activity described by receptor occupancy theory, and the crosstalk and feedback loops for GLP-1-GIP-glucagon, insulin, and glucose.

The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.

Objective: To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis.

Design: Multicentre, double blinded, placebo controlled phase 3 trial.

Setting: 22 centres in China, September 2016 to December 2020.

Pretreatment plasma vitamin D and response to neoadjuvant chemotherapy in breast cancer: evidence from pooled analysis of cohort studies.

Background: Biological evidence has revealed antitumor effect of vitamin D, but whether it could predict the response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients remains inconclusive. The aim was to investigate the association between pretreatment vitamin D level and response to NAC and subsequent survival outcomes in BC patients.

Materials And Methods: The authors systematically searched the Medline, Embase, Cochrane Library, and Web of Science databases and clinical trial registries to identify relevant articles from inception to 8 October 2024.

The diagnostic value and clinical correlations of bone marrow supernatant S100A8 and S100A9 in myelodysplastic neoplasms.

Purpose: Myelodysplastic neoplasms (MDS) are heterogeneous neoplasms that originate from bone marrow (BM) hematopoietic stem cells. S100A8 and S100A9 (S100A8/9) are crucial molecules involved in the innate immune pathogenesis of MDS. This study aimed to explore the value of these molecules in the differential diagnosis of MDS, and analyze the correlations between their concentrations and clinical characteristics.

Neuronal TRPV1-CGRP axis regulates peripheral nerve regeneration through ERK/HIF-1 signaling pathway.

Severe trauma frequently leads to nerve damage. Peripheral nerves possess a degree of regenerative ability, and actively promoting their recovery can help restore the sensory and functional capacities of tissues. The neuropeptide calcitonin gene-related peptide (CGRP) is believed to regulate the repair of injured peripheral nerves, with neuronal transient receptor potential vanilloid type 1 (TRPV1) potentially serving as a crucial upstream factor.

Advances in pharmacological treatment of Cushings disease.

Cushing's disease is a rare endocrine disorder characterized by hypercortisolism. Chronic elevated cortisol levels can lead to dysfunction or complications in multiple organs of systems, including cardiovascular, glucose, and bone metabolism, severely impacting patients' quality of life and posing life-threatening risks. Surgery is the first-line treatment for Cushing's disease.

One-pot ligation of multiple mRNA fragments on dsDNA splint advancing regional modification and translation.

Region-specific RNA modifications are crucial for advancing RNA research and therapeutics, including messenger RNA (mRNA)-based vaccines and immunotherapy. However, the predominant method, synthesizing regionally modified mRNAs with short single-stranded DNA (ssDNA) splints, encounters challenges in ligating long mRNA fragments due to the formation of RNA self-folded complex structures. To address this issue, we developed an efficient strategy using an easily obtained long double-stranded DNA (dsDNA) as a ligation splint after in situ denaturing, while parts of this dsDNA are the templates for transcribing mRNA fragments.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

R(3780) Resonance Interpreted as the 1^{3}D_{1}-Wave Dominant State of Charmonium from Precise Measurements of the Cross Section of e^{+}e^{-}→Hadrons.

We report the precise measurements of the cross section of e^{+}e^{-}→hadrons at center-of-mass energies from 3.645 to 3.871 GeV.

The protein circPETH-147aa regulates metabolic reprogramming in hepatocellular carcinoma cells to remodel immunosuppressive microenvironment.

Metabolic reprogramming fuels cancer cell metastasis and remodels the immunosuppressive tumor microenvironment (TME). We report here that circPETH, a circular RNA (circRNA) transported via extracellular vesicles (EVs) from tumor-associated macrophages (TAMs) to hepatocellular carcinoma (HCC) cells, facilitates glycolysis and metastasis in recipient HCC cells. Mechanistically, circPETH-147aa, encoded by circPETH in an m6A-driven manner, promotes PKM2-catalyzed ALDOA-S36 phosphorylation via the MEG pocket.

EGCG-Modified Bioactive Core-Shell Fibers Modulate Oxidative Stress to Synergistically Promote Vascularized Bone Regeneration.

Oxidative stress induced by reactive oxygen species (ROS) can adversely affect tissue repair, whereas endowing biomaterials with antioxidant activity can improve the in vivo microenvironment, thereby promoting angiogenesis and osteogenesis. Accordingly, this study utilized epigallocatechin-3-gallate (EGCG), a material known for its reducing properties, oxidative self-polymerization capability, and strong binding characteristics, to modify a bioactive core-shell fibrous membrane (10RP-PG). Compared to the 10RP-PG fibrous membrane, the EGCG-modified fibrous membrane (E/10RP-PG) exhibited superior hydrophilicity, excellent cell adhesion, and compatibility.

Modification of gemcitabine with oxaliplatin in China for unresectable gallbladder cancer: a cost-effectiveness analysis.

Background: The incidence of gall bladder cancer (GBC), one of the most prevalent bile duct malignancies, differs with ethnicity and geographic location. To treat unresected GBC in the Chinese setting, this study aimed to assess the financial effectiveness of a combination of modified gemcitabine and oxaliplatin.

Methods: Data from a randomized controlled study in which individuals with metastatic GBC were treated with oxaliplatin and gemcitabine demonstrated improved survival.

The N-terminal domain of gasdermin D induces liver fibrosis by reprogrammed lipid metabolism.

Background: The emerging incidence of pathogenic liver conditions is turning into a major concern for global health. Induction of pyroptosis in hepatocytes instigates cellular disintegration, which in turn liberates substantial quantities of pro-inflammatory intracellular substances, thereby accelerating the advancement of liver fibrosis. Consequently, directing therapeutic efforts towards inhibiting pyroptosis could potentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.

Mirvetuximab Soravtansine in solid tumors: A systematic review and meta-analysis.

Background: Mirvetuximab Soravtansine (MIRV) is a promising antibody‒drug conjugate (ADC) that targets folate receptor alpha (FRα), which is overexpressed in several types of solid tumors. In November 2022, MIRV was approved in the USA for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received 1-3 prior systemic treatment regimens. Therefore, high-quality evidence for its efficacy and safety in different cancers is urgently needed.

Regulation of catechins with different structure characteristics on the physicochemical properties of casein and the structure-activity relationship.

Regulation of catechins with different structure characteristics on the physicochemical properties of casein were investigated, and the structure-activity relationship was further explored. All testing catechins effectively modulated the physicochemical properties of casein, and esterified catechins showed the stronger binding affinity to casein than non-esterified catechins. Catechins significantly altered the secondary and tertiary structures of casein.

Data mining in FAERS: association of newer-generation H1-antihistamines with nervous system disorders.

Background: H1-antihistamines are widely used to treat symptoms depending on histamine release in a variety of conditions. However, neurological adverse events have been reported in post-marketing surveillance studies and there are limited literatures comparing the neurological disorders associated with newer-generation H1-antihistamines from real-world datasets.

Aims: We performed a comparative analysis of nervous system disorders and several newer-generation H1-antihistamines including: cetirizine, loratadine, levocetirizine, desloratadine and fexofenadine.

Glutamine-αKG axis affects dentin regeneration and regulates osteo/odontogenic differentiation of mesenchymal adult stem cells via IGF2 m6A modification.

Background: Multi-lineage differentiation of mesenchymal adult stem cells (m-ASCs) is crucial for tissue regeneration and accompanied with metabolism reprogramming, among which dental-pulp-derived m-ASCs has obvious advantage of easy accessibility. Stem cell fate determination and differentiation are closely related to metabolism status in cell microenvironment, which could actively interact with epigenetic modification. In recent years, glutamine-α-ketoglutarate (αKG) axis was proved to be related to aging, tumorigenesis, osteogenesis etc.

Testing cognitive normal for Alzheimer's disease prediction.

One standing challenge for Alzheimer's disease (AD) research is early diagnosis, which provides a time window for early intervention. Sharmin et al recently reported a positive association between plasma ptau181 and plasma metabolites, medium- and long-chain acylcarnitines (ACs) in both cognitively normal (CN) Aβ- and CN Aβ+ older adults, suggesting a link between initial Aβ pathology and acylcarnitine-mediated energy metabolism pathways. Consistently, ACs could classify PET-Aβ status in elderly individuals.

Addition of SHR-1701 to first-line capecitabine and oxaliplatin (XELOX) plus bevacizumab for unresectable metastatic colorectal cancer.

This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β, in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment for unresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologically confirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients received SHR-1701 (30 mg/kg), bevacizumab (7.

YTHDF2 promotes arsenic-induced malignant phenotypes by degrading PIDD1 mRNA in human keratinocytes.

Arsenic is a widespread environmental carcinogen, and its carcinogenic mechanism has been the focus of toxicology. N-methyladenosine (mA) binding protein YTH domain family protein 2 (YTHDF2) performs various biological functions by degrading mA-modified mRNAs. However, the mA-modified target mRNA of YTHDF2 in regulating arsenic carcinogenesis remains largely unknown.

Self-Assembled EGCG Nanoparticles with Enhanced Intracellular ROS Scavenging for Skin Radioprotection.

Purpose: Skin radiation damage is a prevalent form of tissue injury encountered during radiotherapy, radiation accidents, and occupational exposure. The only clinically approved radioprotective agent, amifostine, is associated with numerous side effects, underscoring the urgent need for the development of safe and effective radioprotective agents. Natural products with reductive properties possess high antioxidant activity and biocompatibility, but their low bioavailability limits their radioprotective efficacy and clinical application.

Shared and disorder-specific large-scale intrinsic and effective functional network connectivities in postpartum depression with and without anxiety.

Postpartum depression and postpartum depression with anxiety, which are highly prevalent and debilitating disorders, become a growing public concern. The high overlap on the symptomatic and neurobiological levels led to ongoing debates about their diagnostic and neurobiological uniqueness. Delineating the shared and disorder-specific intrinsic functional connectivities and their causal interactions is fundamental to precision diagnosis and treatment.

Associations between ethylene oxide exposure and biological age acceleration: evidence from NHANES 2013-2016.

Introduction: Population aging is a global concern, with the World Health Organization predicting that by 2030, one in six individuals worldwide will be 60 years or older. Ethylene oxide (EO) is a widely used industrial chemical with potential health risks, including associations with age-related diseases. This study investigates the relationship between EO exposure and biological age acceleration.