Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma.

Although the spatial characteristics within the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) have been identified, the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear. Using spatial transcriptomics (ST) and single-cell RNA-sequencing (scRNA-seq) data from multi-regional LUAD biopsies, consisting of tumor core, tumor edge and normal area, we sought to delineate the spatial heterogeneity and driving factors of cell co-localization. Two cancer cell sub-clusters (Cancer_c1 and Cancer_c2), associated with LUAD initiation and metastasis respectively, exhibit distinct spatial distributions and immune cell colocalizations.

pH-dependent dissociation from CTLA-4 in early endosomes improves both safety and antitumor activity of anti-CTLA-4 antibodies.

Anti-CTLA-4 Abs (ACAs) are a breakthrough for cancer therapy, but their potential is limited by immunotherapy-related adverse events (irAE). We previously reported that ACAs with acidic pH-sensitive binding to CTLA-4 exhibit higher antitumor activity with fewer irAE. We now test a panel of variants of Ipilimumab (Ipi), the first ACA cancer therapeutic, for tumoricidal efficacy and irAE.

Safety and drug quantification of the dapivirine vaginal ring and oral pre-exposure prophylaxis in breastfeeding mother-infant pairs (MTN-043): a phase 3B, open-label, randomised trial.

Background: In 2021, WHO recommended dapivirine vaginal rings (DVRs) for HIV prevention, but noted evidence gaps for breastfeeding populations. This trial aimed to describe safety profiles associated with DVRs and oral pre-exposure prophylaxis (PrEP) use during breastfeeding and to summarise study-drug quantification and concentrations for mothers and infants.

Methods: Microbicide Trials Network (MTN)-043 was a phase 3b, open-label, randomised trial in which mother-infant pairs were recruited from local health facilities and enrolled at four HIV clinical trial sites in Malawi, South Africa, Uganda, and Zimbabwe.

A multicenter diagnostic study of thyroid nodule with Hashimoto's thyroiditis enabled by Hashimoto's thyroiditis nodule-artificial intelligence model.

Objective: This study aimed to develop a Hashimoto's thyroiditis nodule-artificial intelligence (HTN-AI) model to optimize the diagnosis of thyroid nodules with Hashimoto's thyroiditis (HT) of which the efficiency and accuracy remain challenging.

Design And Methods: This study included 5709 patients from 10 hospitals between January 2014 and March 2024. Among them, 5053 thyroid nodules were divided into training and testing sets in a 9:1 ratio.

Temporal-spatial evolution and formation mechanism of energy consumption carbon footprint at county scale in the Yellow River Basin.

The development and implementation of county carbon control action plans in the Yellow River Basin (YRB) are crucial for realizing the "dual carbon" goals and modernizing national governance. Utilizing remote sensing data from 2001 to 2020, this study constructs a light-carbon conversion model and a carbon footprint model to simulate the carbon footprint of county energy consumption in the YRB. Employing spatial autocorrelation and spatial Durbin models, the study examines the temporal-spatial evolution characteristics and spatial effect mechanism.

Sparking employee's creativity in digital work: A new look on the role of perceived usefulness.

Telecommuting platform is an important medium for collaboration in the digital era and empowering employees to work from anywhere. However, existing research has paid less attention to how employees' perception of telecommuting platform affects their behavior during working from home, especially the impact on their digital creativity. Drawing on self-determination theory, a dual path moderated mediation model was proposed to investigate the effect of perceived usefulness on employees' digital creativity.

Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development.

End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only).

Single-cell RNA sequencing highlights the unique tumor microenvironment of small cell neuroendocrine cervical carcinoma.

Small cell neuroendocrine cervical carcinoma is a highly aggressive tumor characterized by early metastasis, a high recurrence rate, and poor prognosis. This study represents the first instance of single-cell sequencing conducted on small cell neuroendocrine carcinoma of the cervix worldwide. Analysis of gene expression regulatory networks revealed that the transcription factor TFF3 drived up-regulation of ELF3.

Opportunities and challenges of diffusion models for generative AI.

Diffusion models, a powerful and universal generative artificial intelligence technology, have achieved tremendous success and opened up new possibilities in diverse applications. In these applications, diffusion models provide flexible high-dimensional data modeling, and act as a sampler for generating new samples under active control towards task-desired properties. Despite the significant empirical success, theoretical underpinnings of diffusion models are very limited, potentially slowing down principled methodological innovations for further harnessing and improving diffusion models.

Effects of multiple stress events at different stages of life on the incidence of metabolic syndrome.

Objective: To investigate the effects of multiple stress events in different stages of life on the incidence of metabolic syndrome (MetS).

Methods: Miners from Tangshan, China, were recruited for this study. Workers of the Kailuan Mining Group were evaluated to investigate whether exposure to Tangshan earthquakes during the fetal period in 1976.

Influence of Polytetrafluoroethylene Content, Compaction Pressure, and Annealing Treatment on the Magnetic Properties of Iron-Based Soft Magnetic Composites.

To improve the magnetic properties of iron-based soft magnetic composites (SMCs), polytetrafluoroethylene (PTFE) with excellent heat resistance, electrical insulation, and extremely high electrical resistivity was chosen as an insulating coating material for the preparation of iron-based SMCs. The effects of PTFE content, compaction pressure, and annealing treatment on the magnetic properties of Fe/PTFE SMCs were investigated in detail. The results demonstrate that the PTFE insulating layer is successfully coated on the surface of iron powders, which effectively reduces the core loss, increases the resistivity, and improves the frequency stability and the quality factor.

UBR5 mediates colorectal cancer chemoresistance by attenuating ferroptosis via Lys 11 ubiquitin-dependent stabilization of Smad3-SLC7A11 signaling.

Chemoresistance remains a principal culprit for the treatment failure in colorectal cancer (CRC), especially for patients with recurrent or metastatic disease. Deciphering the molecular basis of chemoresistance may lead to novel therapeutic strategies for this fatal disease. Here, UBR5, an E3 ubiquitin ligase frequently overexpressed in human CRC, is demonstrated to mediate chemoresistance principally by inhibiting ferroptosis.

DVsc: An Automated Framework for Efficiently Detecting Viral Infection from Single-cell Transcriptomics Data.

Single-cell RNA sequencing (scRNA-seq) has emerged as a valuable tool for studying cellular heterogeneity in various fields, particularly in virological research. By studying the viral and cellular transcriptomes, the dynamics of viral infection can be investigated at a single-cell resolution. However, limited studies have been conducted to investigate whether RNA transcripts from clinical samples contain substantial amounts of viral RNAs, and a specific computational framework for efficiently detecting viral reads based on scRNA-seq data has not been developed.

MAPK Signaling-Mediated RFNG Phosphorylation and Nuclear Translocation Restrain Oxaliplatin-Induced Apoptosis and Ferroptosis.

Chemotherapy resistance remains a major challenge in the treatment of colorectal cancer (CRC). Therefore, it is crucial to develop novel strategies to sensitize cancer cells to chemotherapy. Here, the fringe family is screened to determine their contribution to chemotherapy resistance in CRC.

Acceptability of the Dapivirine Vaginal Ring and Daily Oral Pre-exposure Prophylaxis (PrEP) during Pregnancy in Malawi, South Africa, Uganda, and Zimbabwe.

Pregnant and lactating persons in sub-Saharan Africa face a heightened risk of HIV acquisition, due to biological and behavioral factors, combined with limited access to prevention and treatment services. Oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring are promising tools for HIV prevention, and the ring's recent approval in multiple African countries represents a significant advancement in expanding access to HIV prevention. In a nested qualitative study within the MTN-042 trial, we explored the acceptability of study products among pregnant persons in the second and early third trimesters.

Bencaosome [16:0 Lyso PA+XLGB28-sRNA] improves osteoporosis by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis in mice.

Osteoporosis (OP) is a systemic metabolic bone disease resulting in reduced bone strength and increased susceptibility to fractures, making it a significant public health and economic problem worldwide. The clinical use of anti-osteoporosis agents is limited because of their serious side effects or the high cost of long-term use. The Xianlinggubao (XLGB) formula is an effective traditional Chinese herbal medicine commonly used in orthopedics to treat osteoporosis; however, its mechanism of action remains unclear.

Construction and Validation of a Nomogram to Identify the Risk of Cavitation in Pulmonary Tuberculosis.

Background: The present study aimed to construct and validate a nomogram based on clinical metrics to identify CPTB.

Patients And Methods: The present study retrospectively recruited pulmonary tuberculosis (PTB) patients admitted to Jiashan County First People's Hospital in China from November 2018 to September 2023. PTB patients were classified into the CPTB group and the non-CPTB group based on chest computed tomography findings, and were randomly allocated to the training set (70%) and the validation cohort (30%).

Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities.

Background: Serotonin (5-hydroxytryptamine) is a multifunctional bioamine serving as a neurotransmitter, peripheral hormone and mitogen in the vertebrate system. It has pleiotropic activities in central nervous system and gastrointestinal function via an orchestrated action of serotonergic elements, particularly serotonin receptor-mediated signalling cascades. The mitogenic properties of serotonin have garnered recognition for years and have been exploited for repurposing serotonergic-targeted drugs in cancer therapy.

Oral administration of herbal oligonucleotide drug JGL-sRNA-h7 ameliorates hyperglycemia in db/db mice and beagle dogs.

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL-sRNA-h7 (B34735529, F1439.

Serum neurofilament light chain and inflammatory cytokines as biomarkers for early detection of mild cognitive impairment.

To investigate the association between serum neurofilament light chain (NfL) levels, inflammatory cytokines, and cognitive function to assess their utility in the early detection of mild cognitive impairment (MCI). We conducted a cross-sectional study involving 157 community-dwelling individuals aged 55 years and above, categorized into healthy controls, MCI, and probable Alzheimer's disease (AD). Serum levels of NfL, inflammatory cytokines, and AD pathology markers were measured using enzyme-linked immunosorbent assay (ELISA).

Dynamic variation in the aroma characteristics of Rhus chinensis honey at different stages after capping.

The ripening characteristics after capping of honey are favourable for improving its quality. However, research on the variation and formation of aroma characteristics of honey in this process is lacking. Therefore, the present study was carried out with different stages of Rhus chinensis honeys (RCHs) after capping and identified 192 volatiles with varying levels of concentration.

M1-type microglia-derived exosomes contribute to blood-brain barrier damage.

Background: As a key substance for intercellular communication, exosomes could be a potential strategy for stroke treatment. Activated microglia disrupt the integrity of blood-brain barrier (BBB) to facilitate the stroke process. Hence, this study was designed to investigate the effect of microglia-derived exosomes on BBB cell model injury and to explore the underlying molecular mechanisms.