Enhancing medical English proficiency: the current status and development potential of peer-assisted learning in medical education.

This narrative review investigates the current implementation and future potential of Peer-Assisted Learning (PAL) in medical education, specifically emphasizing its role in enhancing medical English proficiency. The article analyzes the effectiveness of PAL across various medical education contexts, including primary medical courses, doctor-patient communication, and standardized residency training. The findings indicate that PAL positively impacts student learning outcomes and promotes professional development, highlighting the necessity of its application in medical English instruction.

Identification of de-novo CREBBP gene variants in patients with Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant genetic disease characterized by growth retardation, psychomotor retardation, and distinctive facial features. It is primarily caused by mutations in CREBBP or EP300. In this study, we aimed to describe the clinical manifestations and genetic analyses of two cases with RSTS.

Inhibition of Bruton's tyrosine kinase with PD-1 blockade modulates T cell activation in solid tumors.

BACKGROUNDInhibition of Bruton's tyrosine kinase with ibrutinib blocks the function of myeloid-derived suppressor cells (MDSC). The combination of ibrutinib and nivolumab was tested in patients with metastatic solid tumors.METHODSSixteen patients received ibrutinib 420 mg p.

Prognostic value of albumin-based indices for mortality after heart failure: a systematic review and meta-analysis.

Background: Albumin-based indices have been used to predict mortality after heart failure (HF). We hereby examined the utility of albumin-globin ratio, lactate-albumin ratio, blood urea nitrogen (BUN)-albumin ratio, fibrinogen-albumin ratio, and albumin-bilirubin score (ABS) in predicting mortality after HF.

Methods: We searched Embase, PubMed, Web of Science, and Scopus databases up to 2nd October 2024 for studies examining association between albumin-based indices and mortality after HF.

Spatial and functional targeting of intratumoral Tregs reverses CD8+ T cell exhaustion and promotes cancer immunotherapy.

Intratumoral Tregs are key mediators of cancer immunotherapy resistance, including anti-programmed cell death (ligand) 1 [anti-PD-(L)1] immune checkpoint blockade (ICB). The mechanisms driving Treg infiltration into the tumor microenvironment (TME) and the consequence on CD8+ T cell exhaustion remain elusive. Here, we report that heat shock protein gp96 (also known as GRP94) was indispensable for Treg tumor infiltration, primarily through the roles of gp96 in chaperoning integrins.

Targeting metabolic sensing switch GPR84 on macrophages for cancer immunotherapy.

Introduction: As one of the major components of the tumor microenvironment, tumor-associated macrophages (TAMs) possess profound inhibitory activity against T cells and facilitate tumor escape from immune checkpoint blockade therapy. Converting this pro-tumorigenic toward the anti-tumorigenic phenotype thus is an important strategy for enhancing adaptive immunity against cancer. However, a plethora of mechanisms have been described for pro-tumorigenic differentiation in cancer, metabolic switches to program the anti-tumorigenic property of TAMs are elusive.

MarsGT: Multi-omics analysis for rare population inference using single-cell graph transformer.

Rare cell populations are key in neoplastic progression and therapeutic response, offering potential intervention targets. However, their computational identification and analysis often lag behind major cell types. To fill this gap, we introduce MarsGT: Multi-omics Analysis for Rare population inference using a Single-cell Graph Transformer.

Single-Cell RNA-Seq Analysis of Patient Myeloid-Derived Suppressor Cells and the Response to Inhibition of Bruton's Tyrosine Kinase.

Unlabelled: Myeloid-derived suppressor cell (MDSC) levels are elevated in patients with cancer and contribute to reduced efficacy of immune checkpoint therapy. MDSC express Bruton's tyrosine kinase (BTK) and BTK inhibition with ibrutinib, an FDA-approved irreversible inhibitor of BTK, leads to reduced MDSC expansion/function in mice and significantly improves the antitumor activity of anti-PD-1 antibody treatments. Single-cell RNA sequencing (scRNA-seq) was used to characterize the effect of ibrutinib on gene expression of fluorescence-activated cell sorting-enriched MDSC from patients with different cancer types [breast, melanoma, head and neck squamous cell cancer (HNSCC)].

Asparagine restriction enhances CD8 T cell metabolic fitness and antitumoral functionality through an NRF2-dependent stress response.

Robust and effective T cell immune surveillance and cancer immunotherapy require proper allocation of metabolic resources to sustain energetically costly processes, including growth and cytokine production. Here, we show that asparagine (Asn) restriction on CD8 T cells exerted opposing effects during activation (early phase) and differentiation (late phase) following T cell activation. Asn restriction suppressed activation and cell cycle entry in the early phase while rapidly engaging the nuclear factor erythroid 2-related factor 2 (NRF2)-dependent stress response, conferring robust proliferation and effector function on CD8 T cells during differentiation.

Repression of ferroptotic cell death by mitochondrial calcium signaling.

The uptake of Ca into and extrusion of calcium from the mitochondrial matrix, regulated by the mitochondrial Ca uniporter (MCU), is a fundamental biological process that has crucial impacts on cellular metabolism, signaling, growth and survival. Herein, we report that the embryonic lethality of -deficient mice is fully rescued by orally supplementing ferroptosis inhibitor lipophilic antioxidant vitamin E and ubiquinol. Mechanistically, we found MCU promotes acetyl-CoA-mediated GPX4 acetylation at K90 residue, and K90R mutation impaired the GPX4 enzymatic activity, a step that is crucial for ferroptosis.

IL-27 Gene Therapy Induces Stat3-Mediated Expansion of CD11b+Gr1+ Myeloid Cells and Promotes Accumulation of M1 Macrophages in the Tumor Microenvironment.

IL-27 is a pleiotropic cytokine that exhibits stimulatory/regulatory functions on multiple lineages of immune cells and has a potential to be used as a therapeutic for cancer. We have recently demonstrated that administration of IL-27 producing adeno-associated virus (AAV-IL-27) exhibits potent inhibition of tumor growth in mouse models. In this study, we demonstrate that AAV-IL-27 treatment leads to significant expansion of CD11b+Gr1+ myeloid cells.

LRT: Integrative analysis of scRNA-seq and scTCR-seq data to investigate clonal differentiation heterogeneity.

Single-cell RNA sequencing (scRNA-seq) data has been widely used for cell trajectory inference, with the assumption that cells with similar expression profiles share the same differentiation state. However, the inferred trajectory may not reveal clonal differentiation heterogeneity among T cell clones. Single-cell T cell receptor sequencing (scTCR-seq) data provides invaluable insights into the clonal relationship among cells, yet it lacks functional characteristics.

Aiolos represses CD4 T cell cytotoxic programming via reciprocal regulation of T transcription factors and IL-2 sensitivity.

During intracellular infection, T follicular helper (T) and T helper 1 (T1) cells promote humoral and cell-mediated responses, respectively. Another subset, CD4-cytotoxic T lymphocytes (CD4-CTLs), eliminate infected cells via functions typically associated with CD8 T cells. The mechanisms underlying differentiation of these populations are incompletely understood.

Single-cell biological network inference using a heterogeneous graph transformer.

Single-cell multi-omics (scMulti-omics) allows the quantification of multiple modalities simultaneously to capture the intricacy of complex molecular mechanisms and cellular heterogeneity. Existing tools cannot effectively infer the active biological networks in diverse cell types and the response of these networks to external stimuli. Here we present DeepMAPS for biological network inference from scMulti-omics.

Role of financial development, foreign direct investment inflow, innovation in environmental degradation in Pakistan with dynamic ARDL simulation model.

The purpose of this research is to determine the impact of innovation, economic growth, financial development, trade, foreign direct investment (FDI), electricity consumption, and urbanization on the environmental degradations in Pakistan. This study has employed the dynamic autoregressive distributed lag model (ARDL), to investigate the actual change in the independent variables and its impact on the dependent variable through graphs. The findings demonstrate that energy consumption, GDP growth, urbanization, and trade negatively influence the carbon emissions in the short term.

Can China's renewable energy industry policy support the low-carbon energy transition effectively?

To cope with global climate change and energy security, the realization of the low-carbon energy transition has become an inevitable choice for international carbon emission reduction requirements and energy structure adjustment. Vigorously developing renewable energy has become an essential part of energy policies in many countries. Under the incentive and guidance of renewable energy industry policy, China's renewable energy has developed rapidly, and energy structure has been optimized.

Endothelial Rap1B mediates T-cell exclusion to promote tumor growth: a novel mechanism underlying vascular immunosuppression.

Overcoming vascular immunosuppression: lack of endothelial cell (EC) responsiveness to inflammatory stimuli in the proangiogenic environment of tumors, is essential for successful cancer immunotherapy. The mechanisms through which Vascular Endothelial Growth Factor A(VEGF-A) modulates tumor EC response to exclude T-cells are not well understood. Here, we demonstrate that EC-specific deletion of small GTPase Rap1B, previously implicated in normal angiogenesis, restricts tumor growth in endothelial-specific Rap1B-knockout (Rap1B) mice.

SUSD2 suppresses CD8 T cell antitumor immunity by targeting IL-2 receptor signaling.

Dysfunctional CD8 T cells, which have defective production of antitumor effectors, represent a major mediator of immunosuppression in the tumor microenvironment. Here, we show that SUSD2 is a negative regulator of CD8 T cell antitumor function. Susd2 effector CD8 T cells showed enhanced production of antitumor molecules, which consequently blunted tumor growth in multiple syngeneic mouse tumor models.

Alterations in the vaginal microbiota of patients with preterm premature rupture of membranes.

Background: Preterm premature rupture of membranes (PPROM) is a common pregnancy complication. Yet, the main cause of PPROM remains poorly understood. In this study, we used 16S rRNA gene sequencing technology to identify the differences in vaginal microbiota between pregnant women with PPROM and those who delivered at term.

The use of single-cell multi-omics in immuno-oncology.

Single-cell multi-omics (scMulti-omics) has brought transformative insights into immuno-oncology, demonstrating success in describing novel immune subsets and defining important regulators of antitumor immunity. Here, we give examples of how scMulti-omics has been used in specific tumor studies and discuss how this may develop in the future.

Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation.

Effective T cell-mediated immune responses require the proper allocation of metabolic resources to sustain growth, proliferation, and cytokine production. Epigenetic control of the genome also governs T cell transcriptome and T cell lineage commitment and maintenance. Cellular metabolic programs interact with epigenetic regulation by providing substrates for covalent modifications of chromatin.