Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.

Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.

The involuntary experience of digital exclusion among older adults: A taxonomy and theoretical framework.

The emerging phenomenon of digital exclusion raises an important issue that not everyone is equally engaged in and can benefit from the digital world. Older adults are particularly susceptible to digital exclusion, but a comprehensive conceptual treatment of digital exclusion in older adults is lacking in the psychology literature. In this article, we provide a taxonomy to advance the literature on digital exclusion in older adults, identifying key conceptual attributes of older adults' digital exclusion experiences by articulating both structural (i.

Multi-omics sequencing of gastroesophageal junction adenocarcinoma reveals prognosis-relevant key factors and a novel immunogenomic classification.

Background: Gastroesophageal junction adenocarcinoma (GEJAC) exhibits distinct molecular characteristics due to its unique anatomical location. We sought to investigate effective and reliable molecular classification of GEJAC to guide personalized treatment.

Methods: We analyzed the whole genomic, transcriptomic, T-cell receptor repertoires, and immunohistochemical data in 92 GEJAC patients and delineated the landscape of genetic and immune alterations.

Anti-PD-L1 envafolimab combined with anti-VEGF suvemcitug in pretreated solid tumors and hepatocellular carcinoma: an open-label phase II study with safety run-in stage.

Background: Immune checkpoint inhibitors (ICIs) combined with anti-vascular endothelial growth factor (VEGF) have been the standard first-line treatment of hepatocellular carcinoma (HCC). However, the efficacy of this combination in post-line treatment is still unknown. This study aimed to evaluate the efficacy and safety of the combination of anti-PD-L1 envafolimab and novel humanized anti-VEGF suvemcitug as second-line treatment for patients with HCC.

FOXP3 as a prognostic marker and therapeutic target in immunogenic cell death modulation for clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) remains a challenging cancer type due to its resistance to standard treatments. Immunogenic cell death (ICD) has the potential to activate anti-tumor immunity, presenting a promising avenue for ccRCC therapies.

Methods: We analyzed data from GSE29609, TCGA-KIRC, and GSE159115 to identify ICD-related prognostic genes in ccRCC.

Principles, challenges, and advances in ribosome profiling: from bulk to low-input and single-cell analysis.

Ribosome profiling has revolutionized our understanding of gene expression regulation by providing a snapshot of global translation in vivo. This powerful technique enables the investigation of the dynamics of translation initiation, elongation, and termination, and has provided insights into the regulation of protein synthesis under various conditions. Despite its widespread adoption, challenges persist in obtaining high-quality ribosome profiling data.

Global identification and regulatory network analysis reveal the significant roles of lncRNAs during anther and pollen development in Arabidopsis.

A high-throughput sequencing identified 1283 lncRNAs in anthers at different stages in Arabidopsis and their relationship with protein-coding genes and miRNAs during anther and pollen development were analyzed. Long non-coding RNAs (lncRNAs) are important regulatory molecules involved in various biological processes. However, their roles in male reproductive development and interactions with miRNAs remained elusive.

In-Cell Mass Spectrometry and Ultraviolet Photodissociation Navigates the Intracellular Protein Heterogeneity.

Directly probing the heterogeneous conformations of intracellular proteins within their native cellular environment remains a significant challenge in mass spectrometry (MS). Here, we establish an in-cell MS and ultraviolet photodissociation (UVPD) strategy that directly ejects proteins from living cells into a mass spectrometer, followed by 193 nm UVPD for structural analysis. Applying this approach to calmodulin (CaM), we reveal that it adopts more extended conformations within living cells compared with purified samples , highlighting the unique influence of intracellular environments on protein folding.

Omnidirectionally Stretchable Spin-Valve Sensor Array with Stable Giant Magnetoresistance Performance.

Flexible magnetic sensors, which have advantages such as deformability, vector field sensing, and noncontact detection, are an important branch of flexible electronics and have significant applications in fields such as magnetosensitive electronic skin. Human skin surfaces have complicated deformations, which pose a demand for magnetic sensors that can withstand omnidirectional strain while maintaining stable performance. However, existing flexible magnetic sensor arrays can only withstand stretching along specific directions and are prone to failure under complicated deformations.

Suspect and Nontarget Analysis of Per- and Polyfluoroalkyl Substances in Groundwater Underlying Different Land-Use Areas.

Groundwater can be contaminated by PFAS emissions, yet research on the presence and associated risks of PFAS in groundwater underlying different land-use areas remains limited. Herein, high-resolution mass spectrometry-based suspect and nontarget analyses were performed to determine PFAS occurrence in groundwater samples obtained from a rural area, a planting region, and the vicinities of a pharmaceutical park, an airport, and an industrial park in Datong City, China. A total of 31 PFAS (16 emerging and 15 legacy PFAS) were identified, and the ΣPFAS concentrations ranged from 0.

Design, modeling, and control of coaxial integrated macro-micro composite actuator with high-precision and long-stroke.

This paper presents a coaxial integrated macro-micro composite actuator. The macro-actuator of the macro-micro composite actuator is similar to a moving coil type voice coil motor, and a giant magnetostrictive actuator is installed coaxially inside it as a micro-actuator. In this work, kinetic models are established for both the macro-actuator and micro-actuator, and based on the models, an automatic disturbance rejection controller is adopted to control the macro-actuator, and a fuzzy sliding mode controller is adopted for the micro-actuator.

Neoantigen mRNA vaccines and AA receptor antagonism: A strategy to enhance T cell immunity.

Although neo-antigen mRNA vaccines are promising for personalized cancer therapy, their effectiveness is often limited by the immunosuppressive tumor microenvironment (TME). The adenosine AA receptor (AAR) inhibits dendritic cell (DC) function and weakens antitumor T cell responses through hypoxia-driven mechanisms within the TME. This review explores a novel strategy combining neo-antigen mRNA vaccines with AAR antagonists (AARi).

Solvent-controlled silver catalyzed radical transformation of α-imino-oxy acids with cyclic aldimines.

A silver-catalyzed cross coupling of cyclic aldimines and α-imino-oxy acids has been developed. The solvent-dependent reaction could selectively deliver either cyclic imine moiety retained nitriles or ring-opened oxonitriles in moderate yields. The mechanistic studies show that the reaction undergoes a radical pathway.

Real-world Plasma Exposure of Nirmatrelvir/Ritonavir in Chinese Hospitalized Patients With COVID-19: A Multicenter Retrospective Study.

Background: Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk of progression to severe disease. However, data on the real-world plasma exposure to nirmatrelvir/ritonavir remain limited, particularly in Chinese patients. This study aimed to assess the nirmatrelvir/ritonavir trough concentration (Ctrough) and identify its critical factors in hospitalized Chinese patients treated with nirmatrelvir/ritonavir 300 mg/100 mg twice daily over a 5-day course.

alleviates ischemia-reperfusion injury in steatotic donor liver by inhibiting ferroptosis via the Foxo3-Alox15 signaling pathway.

Ischemia-reperfusion injury (IRI) is a major obstacle in liver transplantation, especially with steatotic donor livers. Dysbiosis of the gut microbiota has been implicated in modulating IRI, and plays a pivotal role in regulating host inflammatory and immune responses, but its specific role in liver transplantation IRI remains unclear. This study explores whether can mitigate IRI and its underlying mechanisms.

Cathepsin B Activatable Fluorescent Probe for Antitumor Efficiency Feedback: Attempt To Detect Certain Apoptotic Cells.

As many treatments kill tumor cells by inducing apoptosis, fluorescent probes that can detect apoptosis are crucial for effective feedback regarding tumor therapy outcomes (in particular, activatable probes for better imaging). Cathepsins are enzymes that are released from lysosomes into the cytoplasm during lysosomal membrane permeabilization-induced apoptosis of many tumor cells, making them potential biomarkers of apoptotic cells. Despite their potential, to the best of our knowledge, no cathepsin-activatable fluorescent probes have been reported for this purpose.

Developing a novel TaqMan qPCR assay for optimizing Pullorum detection in chickens.

Pullorum, the causative agent of pullorum disease, posing a significant threat to the global production of poultry meat and eggs. However, existing detection methods have substantial limitations in efficiency and accuracy. Herein, we developed a genomic deletion-targeted TaqMan qPCR assay for identification of Pullorum, enabling precise differentiation from other serovars.

Comment on: FLT3 ligand kinetic profile predicts response to treatment in patients with high-risk myelodysplastic syndrome / chronic myelomonocytic leukemia receiving CPX-351: a study from the Groupe Francophone des Myélodysplasies.

Not available.

Aging-enhanced autophagy activity promotes fibrotic progression via the TGF-β2/Smad signaling pathway in trabecular meshwork cells-a new insight from POAG.

Introduction: Glaucoma, a leading cause of irreversible blindness, is characterized by optic neuropathy and retinopathy, with primary open-angle glaucoma (POAG) being the most prevalent form. The primary pathogenic mechanism of POAG involves elevated intraocular pressure caused by chronic fibrosis of the trabecular meshwork (TM). Autophagy, a critical process for maintaining cellular homeostasis, has been implicated in fibrosis across various organs.

Difference between estimated glomerular filtration rate based on cystatin C versus creatinine and cardiovascular-kidney-metabolic health.

Background: The difference between the estimated glomerular filtration rate (eGFR) calculated from cystatin C and creatinine (eGFRdiff) serves as a biomarker of kidney function impairment. However, the role of eGFRdiff in cardiovascular-kidney-metabolic (CKM) health and its impact on mortality in CKM syndrome patients has not yet been studied.

Methods: This study included 3,622 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004.

Emerging engineered nanozymes: current status and future perspectives in cancer treatments.

Composite nanozymes are composed of enzymes with similar or different catalytic capabilities and have higher catalytic activity than a single enzyme. In recent years, composite nanozymes have emerged as novel nanomaterial platforms for multiple applications in various research fields, where they are used to produce oxygen, consume glutathione, or produce toxic reactive oxygen species (ROS) for cancer therapy. The therapeutic approach using composite nanozymes is known as chemo-dynamic therapy (CDT).

The Global Burden of Polycystic Ovary Syndrome in Women of Reproductive Age: Findings from the GBD 2019 Study.

Purpose: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and the primary cause of anovulatory infertility among women aged 15-49 years. Despite its significance, it has been largely overlooked in global health discussions, with persistently high prevalence and incidence rates. This public health challenge necessitates attention both domestically and internationally.

Effect of acupuncture on the gait disturbance and hemodynamic changes in the prefrontal cortex: a study protocol for a randomized controlled trial.

Background: Alzheimer's disease (AD) is characterized by cognitive impairment and behavioral impairment. The gait of AD patients is attracting the increasing attention. The aim of this randomized controlled trial (RCT) is to explore the effect of acupuncture on the cognitive function, gait performance, and hemodynamic changes in the prefrontal cortices.

The health effect of relaxing entry regulation for private hospitals and its nonlinear characteristics: evidence from China.

Introduction: Relaxing entry regulation for private hospitals and fostering competition in the healthcare market are crucial prerequisites for addressing the diverse healthcare demands of the population and promoting the development of a Healthy China. This study aims to comprehensively evaluate the health effect of relaxing entry regulation for private hospitals and to examine its nonlinear characteristics.

Methods: Using panel data from 31 provinces in mainland China, this study employs a fixed effects panel data model to investigate the health effect of relaxing entry regulation for private hospitals.