An update on regulation and function of G protein-coupled receptors in cancer: A promising strategy for cancer therapy.

G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that play a crucial role in signal transduction and cellular communication. GPCR proteins are involved in a wide range of physiological processes, including cell growth, migration, and survival. Dysregulation of GPCR protein expression has been implicated in the pathogenesis of various diseases, including cancer, and GPCR proteins have been shown to modulate these processes in various types of cancer, highlighting their importance as potential therapeutic targets.

Mercury levels in freshwater aquatic products across China: Spatial distribution, species differences, and health risk assessment.

Freshwater product consumption is a major source of mercury (Hg) exposure in China. This study analyzed Hg concentrations in 12,560 samples from 29 provinces across China (2010-2021) and conducted probabilistic health risk assessments across various life stages. The average Hg concentration in China's freshwater products was 40.

Screening for immunodominant epitopes of SARS-CoV-2 based on CD8 T cell responses from individuals with HLA-A homozygous alleles.

Purpose: SARS-CoV-2-specific CD8 cytotoxic T lymphocytes (CTLs) are crucial in viral clearance, disease progression, and reinfection control. However, numerous SARS-CoV-2 immunodominant CTL epitopes theoretically are still unidentified due to the genetic polymorphism of human leukocyte antigen class I (HLA-I) molecules.

Methods: The CTL epitopes of SARS-CoV-2 were predicted by the epitope affinity and immunogenicity prediction platforms: the NetMHCpan and the PromPPD.

Long-term exposure to fine particulate matter components with obesity in children and adolescents in China: The age-sex disparities and key effect modifiers.

Long-term fine particulate matter (PM) exposure was associated with childhood obesity. However, the key PM components and whether PM effect may vary by obesity type, growth stage, sex, and individual/family characteristics have yet been examined. In this study, we investigated 213,907 Chinese children and adolescents aged 3-18 years in 2017-2019.

Protocol for investigating astrocytic mitochondria in neurons of adult mice using two-photon microscopy.

Under pathological conditions, astrocytes can transfer mitochondria to neurons, where they exert neuroprotective effects. In this context, we present a protocol for capturing astrocytic mitochondria in neurons of adult mice using a two-photon microscope. We describe an approach for constructing a mouse model with combined labeling of astrocytic mitochondria and neurons.

Suppression of METTL3 expression attenuated matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the extracellular matrix in pelvic organ prolapse.

Background: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP.

Methods: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts.

Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.

Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.

Efficacy and safety of SHEN26, a novel oral small molecular RdRp inhibitor for COVID-19 treatment: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial.

Background: SHEN26 (ATV014) is an oral RNA-dependent RNA polymerase (RdRp) inhibitor with potential anti-SARS-CoV-2 activity. Safety, tolerability, and pharmacokinetic characteristics were verified in a Phase I study. This phase II study aimed to verify the efficacy and safety of SHEN26 in COVID-19 patients.

Comparative evaluation of allograft particulate bone and cortical bone blocks combined with xenograft bone for labial bone defects in the aesthetic zone: a prospective cohort study.

Purpose: This study aimed to evaluate the osteogenic performance of allograft particulate bone and cortical bone blocks combined with xenograft under bovine pericardium membranes, for treating different degrees of labial bone defects in the aesthetic zone.

Materials And Methods: Twenty-four patients with bone defects were divided into two groups based on defect severity (Terheyden 1/4 and 2/4 groups). The Terheyden 1/4 group received granular bone grafts alone, while the Terheyden 2/4 group received cortical bone blocks combined with granular bone grafts.

Identification of a novel TOP2B::AFF2 fusion gene in B-cell acute lymphoblastic leukemia.

Genetic alterations play a pivotal role in leukemic clonal transformation, significantly influencing disease pathogenesis and clinical outcomes. Here, we report a novel fusion gene and investigate its pathogenic role in acute lymphoblastic leukemia (ALL). We engineer a transposon transfection system expressing the TOP2B::AFF2 transcript and introduce it into Ba/F3 cells.

[Clinical characteristics and prognosis of ovarian juvenile granulosa cell tumors].

To analyze the clinical characteristics, treatments, and prognosis of patients with ovarian juvenile granulosa cell tumor (JGCT). Clinical and pathological data, and follow-up information of 34 patients diagnosed with JGCT from 2000 to 2021 were collected from the surveillance, epidemiology, and end results (SEER) database. A retrospective analysis was conducted to summarize the patients' clinical and pathological characteristics, treatments, and prognosis.

[Exploration of CCL11 and sTNFR2 as potential biomarkers for the efficacy of lymphocyte immunotherapy in women with unexplained recurrent spontaneous abortion].

To explore biomarkers for the efficacy of lymphocyte immunotherapy (LIT) treating women with unexplained recurrent spontaneous abortion (URSA). Serum samples from 24 URSA potients who received LIT were collected at Peking University Third Hospital from December 2014 to June 2015. Semiquantitative sandwich-based antibody arrays containing 40 cytokines were used to screen target immune cytokines in the peripheral blood of URSA patients before and after LIT.

Epidemiological status, development trends, and risk factors of disability-adjusted life years due to diabetic kidney disease: A systematic analysis of Global Burden of Disease Study 2021.

Background: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions.

Methods: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location.

Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study.

Objectives: To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and serum cytokine and chemokine profiles as predictors of clinical outcomes in rheumatoid arthritis (RA).

Patients And Methods: We included 200 patients with RA treated with biological and targeted synthetic disease-modifying antirheumatic drugs in a prospective multicentre ultrasound cohort study. Their serum levels of multiple cytokines and chemokines, rheumatoid factors, and serum autoantibodies (anti-cyclic citrullinated peptide-2 (anti-CCP2) and anti-carbamylated protein antibodies) were measured at baseline, 3 months and 12 months.

Novel Hsp90α inhibitor inhibits HSV-1 infection by suppressing the Akt/β-catenin pathway.

The prevalence of herpes simplex virus type 1 (HSV-1) infection and the emergence of drug-resistant HSV-1 strains posts a significant global health challenge, necessitating the urgent development of effective anti-HSV-1 drugs. As one of the most prevalent molecular chaperones, heat shock protein 90 α (Hsp90α) has been extensively demonstrated to regulate a range of viral infections, thus representing a promising antiviral target. In this study, we identified JD-13 as a novel Hsp90α inhibitor and explored its capability in inhibiting HSV-1 infection.

A Cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretion.

Hepatitis B virus (HBV) represents one of the major pathogenic factor that leads to chronic liver diseases and the development of hepatocellular carcinoma (HCC). The currently approved anti-HBV drugs cannot eradicate the virus or block the development of HCC. HBV nucleocapsid consists of the hepatitis B core antigen (HBcAg) and the HBV relaxed-circular partially double-stranded DNA (rcDNA), indispensable in virus replication.

Thrombolytic efficacy and safety of recombinant scu-PA in a rabbit retinal vein occlusion model.

Retinal vein occlusion (RVO) has become the second most common retinal vascular disease after diabetic retinopathy. Existing therapeutic approaches, including intravitreal injection of antivascular endothelial growth factors (anti-VEGFs) and/or glucocorticoids and laser therapy, primarily address secondary macular edema and neovascularisation. However, these strategies do not address the underlying cause of the disease and may have harmful side effects.

Associations of the serum 25-hydroxyvitamin D with mortality among patients in osteopenia or osteoporosis.

Purpose: The correlation between serum vitamin D and mortality in patients with osteopenia or osteoporosis remains unclear. Therefore, this study examined the relationship between serum 25-hydroxy vitamin D [(25(OH)D] and mortality in patients with osteopenia or osteoporosis.

Methods And Result: This prospective cohort study included patients with osteopenia or osteoporosis from the National Health and Nutrition Examination Survey from 2001 to 2018.

The natural product micheliolide promotes the nuclear translocation of GAPDH via binding to Cys247 and induces glioblastoma cell death in combination with temozolomide.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is significantly upregulated in glioblastoma (GBM) and plays a crucial role in cell apoptosis and drug resistance. Micheliolide (MCL) is a natural product with a variety of antitumour activities, and the fumarate salt form of dimethylamino MCL (DMAMCL; commercial name ACT001) has been tested in clinical trials for recurrent GBM; this compound suppresses the proliferation of GBM cells by rewiring aerobic glycolysis. Herein, we demonstrated that MCL directly targets GAPDH through covalent binding to the cysteine 247 (Cys247) residue.

Apathy in Alzheimer's disease: Eye movements characteristics and neurostructural basis.

Background: We sought to evaluate the characteristics of eye movements in Alzheimer's disease (AD) patients with apathy (AD-A) and their ability to identify AD-A and explore the shared neurostructure of eye movements and apathy.

Methods: Total 32 normal controls, 36 AD-A and 72 AD with no apathy (AD-NA) patients were recruited. Parameters of smooth pursuit, fixation, prosaccade and antisaccade were compared among the three groups.

CircKIAA0182 Enhances Lung Cancer Progression and Chemoresistance through Interaction with YBX1.

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality. Resistance to platinum-based chemotherapy, such as cisplatin, significantly limits treatment efficacy. Circular RNAs (circRNAs) have emerged as key regulators of cancer progression and chemotherapy resistance due to their stable structure, which protects them from degradation.

Tertiary Lymphoid Structures as a Biomarker in Immunotherapy and Beyond: Advancing Towards Clinical Application.

Tertiary lymphoid structures (TLSs) are ectopic immune cell clusters formed in nonlymphoid tissues affected by persistent inflammation, such as in cancer and prolonged infections. They have features of the structure and function of secondary lymphoid organs, featuring central CD20+ B cells, surrounded by CD3+ T cells, CD21+ follicular dendritic cells, and CD68+ macrophages, with a complex vascular system. TLS formation is governed by lymphotoxin-α1β2, TNF, and chemokines like CCL19, CCL21, and CXCL13, differing from secondary lymphoid organ development in developing later in life at sites of chronic inflammation.