Inhibition of eEF2 kinase ameliorates hepatic injury induced by ACR through regulation of the MAPK pathway.

Background And Aims: Acrylamide (ACR) induces hepatotoxicity, yet its underlying mechanisms remain incompletely understood. Our prior proteomic analysis of serum from occupationally ACR-exposed individuals identified significantly elevated levels of eukaryotic elongation factor 2 (eEF2). Given that eEF2 activity is regulated by its phosphorylation status, which is solely mediated by eukaryotic elongation factor 2 kinase (eEF2K), we investigated the role of eEF2K in ACR-induced hepatic injury.

[NSD1 regulates H3K36me2 in the pathogenesis of non-obstructive azoospermia].

Objective: To explore the role of nuclear receptor-binding SET-domain protein 1 (NSD1) in the pathogenesis of nonobstructive azoospermia (NOA) by regulating the expressions of relevant genes.

Methods: We detected the expression of NSD1 in the testis tissue of 7 male patients with obstructive azoospermia (OA) and 18 with NOA by qPCR and immunofluorescence assay, and determined the modification level of H3K36me2 in the testes of two groups of patients by immunofluorescence staining, Western blot and immunoprecipitation (IP). We examined the difference in the enrichment of H3K36me2 in the testis tissue by chromatin IP-based sequencing (ChIP-Seq), analyzed the genomic distribution and target genes using bioinformatics, and verified the expression levels of the target genes in the testes of the two groups of patients by qPCR.

Association between alcoholic beverage consumption and cerebral small vessel disease burden.

Background: The relationship between alcohol consumption and cerebral small vessel disease (CSVD) remains uncertain, particularly regarding drinking patterns and beverage types. We investigated how total alcohol intake, drinking frequency, and beverage-specific consumption are associated with CSVD burden using cross-sectional data.

Methods: We included 27,326 UK Biobank (UKB) participants with MRI data, among whom 21,130 were current drinkers with full alcohol intake data.

Predictive factors and nomogram for the risk of cytokine release syndrome with anti-CD3 × CD20 bispecific antibodies for Chinese patients.

Background: Targeting CD3 × CD20 bispecific antibodies (BsAbs) represents a new milestone in the salvage therapy of relapsed/relapsed large B cell lymphoma and follicular lymphoma. However, cytokine release syndrome (CRS) remains one of the major concerns in clinical practice of CD3 × CD20 BsAbs. This study aimed to identify the potential predictive factors and to construct a nomogram of grade ≥ 2 CRS in CD3 × CD20 BsAbs in Chinese patients.

Safety and efficacy of the selective TYK2/JAK1 inhibitor TLL-018 in moderate-to-severe plaque psoriasis: A phase 1b, randomized, double-blind, placebo-controlled study.

Background: Psoriasis treatments that provide rapid and extensive itch relief, lesion clearance are inadequate.

Objective: To evaluate the efficacy and safety of the tyrosine kinase 2/Janus kinase 1 inhibitor TLL-018 in patients with moderate-to-severe psoriasis.

Methods: This phase 1b, double-blind, placebo-controlled study randomized participants to receive TLL-018 (2:2:2:1) 10:20:30 mg:placebo (12 weeks) twice daily (BID) orally (NCT05342428).

Extranodal diffuse large B-cell lymphoma: Clinical and molecular insights with survival outcomes from the multicenter EXPECT study.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin's lymphoma with distinct clinical and molecular heterogeneity. DLBCL that arises in extranodal organs is particularly linked to poor prognosis. This study aimed to determine the clinical and molecular characteristics of extranodal involvement (ENI) in DLBCL and assess the actual survival status of the patients.

PI3Kδ inhibitor linperlisib combined with gemcitabine and oxaliplatin for relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase Ib/II trial.

Background: This investigation assessed the therapeutic potential of combining linperlisib, a targeted inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), with gemcitabine and oxaliplatin (GEMOX) for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Methods: This was a multicenter, phase Ib/II clinical study conducted across six sites in China, enrolling 39 individuals with histologically confirmed R/R DLBCL. The treatment protocol included oral linperlisib alongside GEMOX administered intravenously every three weeks for up to six cycles.

Modified Cuff Leak Test for Predicting the Risk of Reintubation in Patients With Invasive Mechanical Ventilation: A Multicenter, Single-Anonymized, Randomized Controlled Trial.

Background: The cuff leak test (CLT) is an important tool to assess the risk of upper airway obstruction after extubation.

Research Question: Does a modified CLT approach have superior ability in predicting reintubation compared with the traditional method?

Study Design And Methods: This was a prospective, multicenter, randomized controlled trial. The primary end point was the incidence of the need for reintubation within 48 hours of extubation.

Susceptibility of Mitophagy-Deficient Tumors to Ferroptosis Induction by Relieving the Suppression of Lipid Peroxidation.

The identification of ferroptosis-sensitive cancers is critical for the application of ferroptosis-inducing therapies in cancer therapy. Here, patient-derived organoid screening models of colorectal cancer are established to identify tumors that are sensitive to ferroptosis-inducing therapy. This study discovers that patient-derived tumors characterized by mitophagy deficiency are hypersensitive to ferroptosis-inducing therapies.

Species recognition and the divergences in the chemical and ultrasonic signals between two coexisting species.

The ability to recognize and differentiate between conspecifics and heterospecifics as well as their signals is critical for the coexistence of closely related species. In the genus , species are morphologically similar and multiple species often coexist. Here, we investigated the interspecific recognition and signal differentiation of two sympatric rat species, the brown rat (, RN) and the Asian house rat (, RT).

S-propargyl-cysteine promotes the stability of atherosclerotic plaque via maintaining vascular muscle contractile phenotype.

Plaque rupture in atherosclerosis contributes to various acute cardiovascular events. As a new sulfide-containing donor, S-propargyl-cysteine (SPRC) has been reported to play a beneficial role in cardioprotection, potentially through its anti-inflammatory, anti-oxidative and anti-atherogenic activities. Our previous study observed an increase in eNOS phosphorylation in endothelial cells.

Enhancer of Zeste Homolog 2 Inhibitor SHR2554 in Relapsed or Refractory Peripheral T-cell Lymphoma: Data from the First-in-Human Phase I Study.

Purpose: Patients with peripheral T-cell lymphomas (PTCL) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas.

Patients And Methods: This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms.

Epstein-Barr virus-based prognostic model in nodular sclerosis classic Hodgkin lymphoma.

The role of Epstein-Barr virus (EBV) in lymphoma cells of nodular sclerosis classic Hodgkin lymphoma (NScHL) is controversial. Our aim was to explore this and establish a clinically feasible model for risk stratification. We interrogated data from 542 consecutive subjects with NScHL receiving ABVD therapy and demonstrated EBV-infection in their lymphoma cells with EBV-encoded small RNAs (EBERs) hybridization.

Photocatalytic Three-Component Reaction for the Synthesis of Multifunctional Diaryl Sulfides.

A photocatalytic three-component reaction of a nitroarene, a thiophenol, and a ketone for the synthesis of multifunctional diaryl sulfides was reported using a nitro group as the nitrogen source and thiophenol as the sulfur source. Thiophenol also serves as a proton donor to reduce nitroarene to arylamine as a key intermediate for the formation of C-N and C-S bonds. Good functional group tolerance and mild reaction conditions make this method have practical synthetic value for diversified multifunctional diaryl sulfides.

DPP-IV Inhibitory Peptides from Coix Seed Prolamins: Release, Identification, and Analysis of the Interaction between Key Residues and Enzyme Domains.

Dipeptidyl peptidase IV (DPP-IV) inhibitory peptides can regulate type 2 diabetes by inhibiting the cleavage of glucagon-like peptide-1 and prolonging its half-life. The development of DPP-IV inhibitory peptides is still a hot topic. The primary structure of coix seed prolamins contains peptide sequence fragments that potentially inhibit DPP-IV; however, limited information is available regarding the extraction of peptides from coix seeds and the analysis of their conformational relationships.

A systematic review: on the mercaptoacid metabolites of acrylamide, N-acetyl-S-(2-carbamoylethyl)-L-cysteine.

Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs.

Processing Enhances Coix Seed Prolamins Structure and Releases Functional Peptides after Digestion: In Silico and In Vitro Studies.

Dipeptidyl peptidase-IV (DPP-IV) is a key target for the treatment of type 2 diabetes mellitus. It is possible that peptides that precisely regulate DPP-IV could be released from coix seed prolamins (CSP), but whether this happens has not yet been investigated. We performed the in silico digestion of CSP and predicted the bioactivity, absorption, transport, toxicity, and allergenicity of the resulting peptides.

S-propargyl-cysteine delays the progression of atherosclerosis and increases eNOS phosphorylation in endothelial cells.

The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control.