Long term latency of highly mutated cells in normal mouse skin is reversed by exposure to tumor promoters and chronic tissue damage.

Historical studies performed nearly a century ago using mouse skin models identified two key steps in cancer evolution: initiation, a likely mutational event, and promotion, driven by inflammation and cell proliferation. Initiation was proposed to be permanent, with promotion as the critical rate-limiting step for cancer development. Here, we carried out whole genome sequencing to demonstrate that initiated cells with thousands of mutagen-induced mutations can persist for long periods and are not removed by cell competition or by immune intervention, thus mimicking the persistence of cells with cancer driver mutations in normal human tissues.

Ultrasensitive, Real-Time Detection of Viral Antigens and RNA Enabled by Scalable Graphene-Based FET Sensors for Pathogen Detection: A Case Study on COVID-19.

Herein, a novel and simple electrospray (ES) printing technique was developed for the fabrication of ultrathin graphene layers with precisely controlled nanometer-scale thickness, where graphene oxide (GO) was electrosprayed on wafers and subsequently chemically reduced into reduced GO (rGO). Utilizing that technique, we prepared ultrathin rGO in-plane graphene field-effect transistor (GFET)-based biosensors coupled with a portable prototype measuring system for point-of-care detection of pathogens. We illustrate the use of such prepared GFETs to detect COVID-19, using the SARS-CoV-2 nucleocapsid protein antigen (N-protein) and genomic viral RNA as detection targets.

Large-scale dependency and drug screens characterize the therapeutic vulnerabilities of Multiple Myeloma with 1q.

The development of targeted therapy for patients with multiple myeloma (MM) is hampered by the low frequency of actionable genetic abnormalities. Gain or amplification of chromosome 1q (1q+) is the most frequent arm-level copy number gain in patients with MM and is associated with higher risk of progression and death despite recent therapeutic advances. Thus, developing targeted therapy for MM patients with 1q+ stands to benefit a large portion of patients in need of more effective management.

Adhesion-Assisted Antioxidant-Engineered Mesenchymal Stromal Cells for Enhanced Cardiac Repair in Myocardial Infarction.

Mesenchymal stromal cell (MSC) therapy holds great promise for treating myocardial infarction (MI). However, the inflammatory and reactive oxygen species (ROS)-rich environment in infarcted myocardium challenges MSC survival, limiting its therapeutic impact. In this study, we demonstrate that chemical modification of MSCs with anti-VCAM1 and polydopamine (PD) significantly enhances MSC survival and promotes cardiac repair.

Inflammatory Microenvironment-Modulated Conductive Hydrogel Promotes Vascularized Bone Regeneration in Infected Bone Defects.

Infected bone defects show a significant reduction in neovascularization during the healing process, primarily due to persistent bacterial infection and immune microenvironmental disorders. Existing treatments are difficult to simultaneously meet the requirements of antibacterial and anti-inflammatory treatments for infected bone defects, which is a key clinical therapeutic challenge that needs to be addressed. In this study, a conductive hydrogel based on copper nanoparticles was developed for controlling bacterial infection and remodeling the immune microenvironment.

CAD manipulates tumor intrinsic DHO/UBE4B/NF-κB pathway and fuels macrophage cross-talk, promoting hepatocellular carcinoma metastasis.

Background And Aims: Portal vein tumor thrombosis (PVTT), an indicator of clinical metastasis, significantly shortens hepatocellular carcinoma (HCC) patients' lifespan, and no effective treatment has been established. We aimed to illustrate mechanisms underlying PVTT formation and tumor metastasis, and identified potential targets for clinical intervention.

Approach And Results: Multi-omics data of 159 HCC patients (including 37 cases with PVTT) was analyzed to identify contributors to PVTT formation and tumor metastasis.

Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2.

As one of the earliest identified susceptible animals for the SARS-CoV-2, cats are also the vulnerable hosts for feline coronaviruses, ie feline enteric coronavirus (FECV). Here, to understand the cross-presentation of coronavirus-derived peptides by cat major histocompatibility complex molecule feline leucocyte antigen (FLA) class I, unpredictable natural peptide motifs presented by FLA-K*00701 and FLA-E*00301 were identified through peptide elution and further confirmed by the structural determination of the 2 FLA class I molecules. Based on these precise motifs of FLA class I peptides, the atlas of cross-presenting peptides from different coronaviruses in cats were sketched with 3 hotspots in C-terminal half of ORF1ab protein.

Teleost IgM+ plasma-like cells: beyond antibody secretion.

Upon antigen encounter, B cells start a differentiation process toward antibody-secreting cells (ASCs), initially plasmablasts, and eventually long-lived plasma cells. All these ASCs specialize in secreting important amounts of antibodies and usually lose other functionalities of naïve B cells. This differentiation process is scarcely characterized in teleost fish, in which B cells have been shown to share many functional and phenotypic characteristics of mammalian B1 innate subsets.

Heterogeneous cellular responses to hyperthermia support combined intraperitoneal hyperthermic immunotherapy for ovarian cancer mouse models.

The benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer remains controversial, hindering the development of rational combination therapies based on hyperthermia (HT). This study reports the preliminary results of the neoadjuvant HIPEC (NHIPEC) trial (ChiCTR2000038173), demonstrating enhanced tumor response in high-grade serous ovarian cancer with NHIPEC. Through single-cell RNA sequencing analysis, we identified both homogeneous and heterogeneous cellular responses to HT within the tumor and microenvironment.

Shaping early neural development by timed elevated tissue oxygen tension: Insights from multiomic analysis on human cerebral organoids.

Oxygen plays a critical role in early neural development in brains, particularly before establishment of complete vasculature; however, it has seldom been investigated due to technical limitations. This study uses an in vitro human cerebral organoid model with multiomic analysis, integrating advanced microscopies and single-cell RNA sequencing, to monitor tissue oxygen tension during neural development. Results reveal a key period between weeks 4 and 6 with elevated intra-organoid oxygen tension, altered energy homeostasis, and rapid neurogenesis within the organoids.

Genetically supported targets and drug repurposing for brain aging: A systematic study in the UK Biobank.

Brain age gap (BAG), the deviation between estimated brain age and chronological age, is a promising marker of brain health. However, the genetic architecture and reliable targets for brain aging remains poorly understood. In this study, we estimate magnetic resonance imaging (MRI)-based brain age using deep learning models trained on the UK Biobank and validated with three external datasets.

FlyVISTA, an integrated machine learning platform for deep phenotyping of sleep in .

There is great interest in using genetically tractable organisms such as to gain insights into the regulation and function of sleep. However, sleep phenotyping in has largely relied on simple measures of locomotor inactivity. Here, we present FlyVISTA, a machine learning platform to perform deep phenotyping of sleep in flies.

FAP-catalyzed in situ self-assembly of magnetic resonance imaging probe for early and precise staging of liver fibrosis.

Liver fibrosis is an inevitable stage in the progression of most chronic liver diseases. Early diagnosis and treatment of liver fibrosis are crucial for effectively managing chronic liver conditions. However, there lacks a noninvasive and sensitive imaging method capable of early assessing fibrosis activity.

Splenic red pulp macrophages eliminate the liver-resistant from the blood circulation of mice.

Invasive infections by encapsulated bacteria are the major cause of human morbidity and mortality. The liver resident macrophages, Kupffer cells, form the hepatic firewall to clear many encapsulated bacteria in the blood circulation but fail to control certain high-virulence capsule types. Here we report that the spleen is the backup immune organ to clear the liver-resistant serotypes of (pneumococcus), a leading human pathogen.

Immune memory in hepatitis E virus: a comparative study of natural infection and vaccination in a nursing home population.

Immune memory is crucial for preventing hepatitis E virus (HEV) infection. Our study aims to investigate immunological memory characteristics and differences between vaccination and natural HEV infection, taking into account that both can induce immune memory. We recruited 60 HEV-infected patients, 58 contingency HEV-vaccinated individuals and 4 controls from an outbreak of hepatitis E in a nursing home between June and August 2023.

Frequent Hand Hygiene-Induced Skin Symptoms and Alterations in Hand Microbiota: A Neglected Form of Chronic Occupational Exposure Among Health Care Workers.

Background: Frequent hand hygiene is essential for infection control among health care workers (HCWs) but may cause adverse skin effects.

Purpose: To assess the relationships between frequent hand hygiene practices, skin symptoms, and microbiota alterations in HCWs.

Methods: A comprehensive search of 7 databases was conducted to identify articles published between January 2014 and July 2024 in English and Chinese.

Genetic or therapeutic disruption of the Reelin/Apoer2 signaling pathway improves inflammatory arthritis outcomes.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, pannus formation, and progressive joint destruction. The inflammatory milieu in RA drives endothelial cell activation and upregulation of adhesion molecules, thus facilitating leukocyte infiltration into the synovium. Reelin, a circulating glycoprotein previously implicated in endothelial activation and leukocyte recruitment in diseases such as atherosclerosis and multiple sclerosis, has emerged as a potential upstream regulator of these processes.

Proteasomal processing of the viral replicase ORF1 facilitates HEV-induced liver fibrosis.

Chronic infections with hepatitis E virus (HEV), especially those of genotype 3 (G3), frequently lead to liver fibrosis and cirrhosis in patients. However, the causation and mechanism of liver fibrosis triggered by chronic HEV infection remain poorly understood. Here, we found that the viral multiple-domain replicase (ORF1) undergoes unique ubiquitin-proteasomal processing leading to formation of the EV-erived MAD ctivator (HDSA), a viral polypeptide lacking putative helicase and RNA polymerase domains.

Analysis of the release pattern of floral aroma components of Rhus chinensis based on HS-SPME-GC-MS technique.

Rhus chinensis, a native plant species of China, possesses significant economic value in the ornamental sector. This study investigates the floral fragrance components and release patterns of R. chinensis, thus providing a theoretical foundation for the utilization of its floral fragrance.

The impact of work-family conflict on job burnout among community social workers in China.

In China, for community social workers, work-family conflict has become a common phenomenon that may harm their well-being. Based on the analysis of a survey of community social workers in four cities in China, this study demonstrated that community workers' work-family conflict significantly affects burnout, role overload mediates the relation between work-family conflict and burnout, and cognitive crafting negatively moderates the relation between role overload and burnout. The conclusions validate the job crafting theory and enrich the research on job burnout under the JD-R model.

Inhibition Effect of HO on the Heterogeneous Reaction between Isoprene and Fe-Substituted Cryptomelane.

The transportation and transformation of biogenic isoprene are vital for the organic carbon cycle in the troposphere. As a typical mineral with high oxidation potential, Fe-substituted cryptomelane oxidizes the surface monolayer of isoprene into formic and acetic acids, and simultaneously, the Mn ions in the structure are reduced to Mn and Mn. The flow of HO in isoprene decreases the adsorption and oxidation of isoprene significantly, even at low relative humidity (10%).

Biodetoxification of both AFB1 and ZEN by Bacillus subtilis ZJ-2019-1 in gastrointestinal environment and in mice.

Aflatoxin B1 (AFB1) and zearalenone (ZEN) are the most prevalent mycotoxins in production, posing a serious threat to human and animal health. Therefore, it is very urgent to find a safe and efficient method for the biodegradation of these mycotoxins. Our previous study demonstrated that Bacillus subtilis ZJ-2019-1 moderately degrades both mycotoxins in vitro and ZEN in female gilts.

Cystopexy following anterior-approach robot-assisted radical prostatectomy enhances early continence recovery.

To evaluate the effect of cystopexy on continence recovery after anterior-approach transperitoneal robot-assisted radical prostatectomy (RaRP). We retrospectively analyzed continence recovery of patients with prostate cancer receiving RaRP in a transperitoneal anterior-approach manner with or without cystopexy. Continence recovery is defined as complete intact continence without safety pad utility.

Design Refinement of Catalytic System for Scale-Up Mild Nitrogen Photo-Fixation.

Ammonia and nitric acid, versatile industrial feedstocks, and burgeoning clean energy vectors hold immense promise for sustainable development. However, Haber-Bosch and Ostwald processes, which generates carbon dioxide as massive by-product, contribute to greenhouse effects and pose environmental challenges. Thus, the pursuit of nitrogen fixation through carbon-neutral pathways under benign conditions is a frontier of scientific topics, with the harnessing of solar energy emerging as an enticing and viable option.

System metabolic engineering modification of Saccharomyces cerevisiae to increase SAM production.

S-adenosyl-L-methionine (SAM) is an important compound with significant pharmaceutical and nutraceutical applications. Currently, microbial fermentation is dominant in SAM production, which remains challenging due to its complex biosynthetic pathway and insufficient precursor availability. In this study, a multimodule engineering strategy based on CRISPR/Cas9 was established to improve the SAM productivity of Saccharomyces cerevisiae.