Calcineurin governs baseline and homeostatic regulations of non-rapid eye movement sleep in mice.

Sleep need accumulates during waking and dissipates during sleep to maintain sleep homeostasis (process S). Besides the regulation of daily (baseline) sleep amount, homeostatic sleep regulation commonly refers to the universal phenomenon that sleep deprivation (SD) causes an increase of sleep need, hence, the amount and intensity of subsequent recovery sleep. The central regulators and signaling pathways that govern the baseline and homeostatic sleep regulations in mammals remain unclear.

Life satisfaction around the world: Measurement invariance of the Satisfaction With Life Scale (SWLS) across 65 nations, 40 languages, gender identities, and age groups.

The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions.

PTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers.

BRAF mutations drive initiation and progression of various tumors. While BRAF inhibitors are effective in BRAF-mutant melanoma patients, intrinsic or acquired resistance to these therapies is common. Here, we identify non-receptor-type protein tyrosine phosphatase 23 (PTPN23) as an alternative effective target in BRAF-mutant cancer cells.

Barcoded screening identifies nanocarriers for protein delivery to kidney.

Targeted protein delivery with nanocarriers holds significant potential to enhance therapeutic outcomes by precisely directing proteins to specific organs or tissues. However, the complex interactions between nanocarriers and the biological environment pose considerable challenges in designing effective targeted delivery vehicles. In this study, we address this challenge by leveraging DNA-barcoded high-throughput screening.

Consensus and guidelines on diagnosis and management of polypoidal choroidal vasculopathy (PCV) from the Asia-Pacific Vitreo-retina Society (APVRS).

A panel of 21 international experts are formed by the Asia-Pacific Vitreo-retina Society to work out the consensus and guidelines on polypoidal choroidal vasculopathy (PCV). PCV is a common subtype of neovascular age-related macular degeneration and is more prevalent in Asian populations. Recent advancement in imaging technology allows greater understanding of the disease process of PCV.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM) infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression. Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic. The extent of GBM integration into the brain-wide neuronal circuitry remains unclear.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

MMFuncPhos: A Multi-Modal Learning Framework for Identifying Functional Phosphorylation Sites and Their Regulatory Types.

Protein phosphorylation plays a crucial role in regulating a wide range of biological processes, and its dysregulation is strongly linked to various diseases. While many phosphorylation sites have been identified so far, their functionality and regulatory effects are largely unknown. Here, a deep learning model MMFuncPhos, based on a multi-modal deep learning framework, is developed to predict functional phosphorylation sites.

Deep imaging of LepR stromal cells in optically cleared murine bone hemisections.

Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional (3D) architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions. Deciphering the spatial interaction of leptin receptor-expressing (LepR) stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue. In this study, we introduce an optimized protocol for the 3D analysis of skeletal tissues, enabling the visualization of hematopoietic and stromal cells, especially LepR stromal cells, within optically cleared bone hemisections.

Inflammatory bowel disease increases the risk of pancreatitis: a two-sample bidirectional Mendelian randomization analysis.

Background: Previous studies have suggested an association between inflammatory bowel disease (IBD), and pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). We aimed to examine the potential causal relationship between IBD and pancreatitis using the Mendelian randomization (MR) method.

Methods: We obtained data from genome-wide association studies (GWASs) in European individuals for IBD and its main subtypes, Crohn's disease (CD) and ulcerative colitis (UC) (31,665 IBD cases, 13,768 UC cases, 17,897 CD cases and 33,977 controls).

Costs of Influenza Illness and Acute Respiratory Infections by Household Income Level: Catastrophic Health Expenditures and Implications for Health Equity.

Background: Seasonal influenza illness and acute respiratory infections can impose a substantial economic burden in low- and middle-income countries (LMICs). We assessed the cost of influenza illness and acute respiratory infections across household income strata.

Methods: We conducted a secondary analysis of data from a prior systematic review of costs of influenza and other respiratory illnesses in LMICs and contacted authors to obtain data on cost of illness (COI) for laboratory-confirmed influenza-like illness and acute respiratory infection.

Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells.

Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions.

The Induction of Disease Resistance by Scopolamine and the Application of Extract Against Potato ( L.) Late Blight.

Late blight, caused by , is a devastating disease of potato. Our previous work illustrated that scopolamine, the main bioactive substance of extract, exerts direct inhibitory effects on , but it is unclear whether scopolamine and extract can boost resistance to late blight in potato. In this study, .

Single-cell transcriptomic analysis of chondrocytes in cartilage and pathogenesis of osteoarthritis.

Chondrocyte is considered the only cell type in cartilage. However, the cell heterogeneity of chondrocytes in human articular cartilage is still not well defined, which hinders our understanding of the pathogenesis of osteoarthritis (OA). Here, we constructed a single-cell transcriptomic atlas of chondrocytes in healthy cartilage and identified nine chondrocyte subsets including homeostatic chondrocytes, proliferate fibrochondrocytes, and hypertrophic chondrocytes (HTC).

PD-1/PD-L1 inhibitors related adverse events: A bibliometric analysis from 2014 to 2024.

Programmed cell death-1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors are considered effective alternatives for the primary treatment of recurrent metastatic cancers. However, they can induce various adverse events affecting multiple organ systems, potentially diminishing patients' quality of life, and even leading to treatment interruptions. Adverse events related to PD-1/PD-L1 inhibitors differ from those associated with CTLA-4 inhibitors and are more commonly observed in the treatment of solid tumors.

Calcium/calmodulin-dependent protein kinase II α and β differentially regulate mammalian sleep.

While sleep is important, our understanding of its molecular mechanisms is limited. Over the last two decades, protein kinases including Ca/calmodulin-dependent protein kinase II (CaMKII) α and β have been implicated in sleep regulation. Of all the known mouse genetic mutants, the biggest changes in sleep is reported to be observed in adult mice with sgRNAs for Camk2b injected into their embryos: sleep is reduced by approximately 120 min (mins) over 24 h (hrs).

Use and knowledge of the two FIGO systems for nongestational abnormal uterine bleeding in the reproductive years: A multinational survey.

Objective: To evaluate the worldwide use of FIGO's two systems for the classification of causes and contributors to nongestational abnormal uterine bleeding in the reproductive years by obstetrics and gynecology professionals worldwide, to identify knowledge gaps, and explore barriers to implementation.

Methods: An electronic survey was developed by members of FIGO's Menstrual Disorders and Related Health Impacts (MDRHI) Committee to assess knowledge of abnormal uterine bleeding (AUB) and the two FIGO AUB systems among obstetricians and gynecologists. The survey was conducted online from February 28 to June 30, 2023, and comprised demographic questions, educational content inquiries, and a knowledge assessment.

Preoperative estimated glomerular filtration rate to predict cardiac events in major noncardiac surgery: a secondary analysis of two large international studies.

Background: Optimised use of kidney function information might improve cardiac risk prediction in noncardiac surgery.

Methods: In 35,815 patients from the VISION cohort study and 9219 patients from the POISE-2 trial who were ≥45 yr old and underwent nonurgent inpatient noncardiac surgery, we examined (by age and sex) the association between continuous nonlinear preoperative estimated glomerular filtration rate (eGFR) and the composite of myocardial injury after noncardiac surgery, nonfatal cardiac arrest, or death owing to a cardiac cause within 30 days after surgery. We estimated contributions of predictive information, C-statistic, and net benefit from eGFR and other common patient and surgical characteristics to large multivariable models.

DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.

DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2.

Advancements in research and clinical management of interstitial lung injury associated with ADC drugs administration in breast cancer.

Antibody-drug conjugates (ADCs) represent a novel class of targeted anti-tumor medications that utilize the covalent linkage between monoclonal antibodies and cytotoxic agents. This unique mechanism combines the cytotoxic potency of drugs with the targeting specificity conferred by antigen recognition. However, it is essential to recognize that many ADCs still face challenges related to off-target toxicity akin to cytotoxic payloads, as well as targeted toxicity and other potential life-threatening adverse effects, such as treatment-induced interstitial lung injury.

Climate change linked to vampire bat expansion and rabies virus spillover.

Bat-borne pathogens are a threat to global health and in recent history have had major impacts on human morbidity and mortality. Examples include diseases such as rabies, Nipah virus encephalitis, and severe acute respiratory syndrome (SARS). Climate change may exacerbate the emergence of bat-borne pathogens by affecting the ecology of bats in tropical ecosystems.

Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy.

Diabetic kidney disease (DKD), one of the most prevalent microvascular complications of diabetes, arises from dysregulated glucose and lipid metabolism induced by hyperglycemia, resulting in the deterioration of renal cells such as podocytes and tubular epithelial cells. Programmed cell death (PCD), comprising apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis, represents a spectrum of cell demise processes intricately governed by genetic mechanisms in vivo. Under physiological conditions, PCD facilitates the turnover of cellular populations and serves as a protective mechanism to eliminate impaired podocytes or tubular epithelial cells, thereby preserving renal tissue homeostasis amidst hyperglycemic stress.

Recurrent strokes after transcatheter aortic valve replacement in an elderly patient with severe bicuspid aortic valve stenosis: a case report.

Background: Transcatheter aortic valve replacement (TAVR) has evolved from a novel technology to an established therapy for high-risk patients with symptomatic severe aortic valve stenosis (AS). Recently, its use has also been extended to low-risk patients, resulting in its increasing utilization in patients with bicuspid aortic valve (BAV). But as a serious post-TAVR complication, ischemic stroke was associated with a nearly 6-fold increased 30-day mortality.

Reproductive factors and risk of epithelial ovarian cancer: results from the Asia Cohort Consortium.

Background: There are scarce data on risk factors for epithelial ovarian cancer (EOC) in Asian populations. Our goal was to advance knowledge on reproductive -related risk factors for EOC in a large population of Asian women.

Methods: This study used pooled individual data from baseline questionnaires in 11 prospective cohorts (baseline years, 1958-2015) in the Asia Cohort Consortium.

Comparison of postoperative radiotherapy and definitive radiotherapy for non-metastatic adenoid cystic carcinoma of the head and neck, a propensity score matching based on the SEER database.

Background: Treating patients with head and neck adenoid cystic carcinoma (HNACC) presents surgical problems in various scenarios. Limited studies explore definitive radiation's impact on patient survival, with inadequate data correlating it to postoperative radiotherapy. Using the Surveillance, Epidemiology, and End Results (SEER) program, we conducted an objective analysis to evaluate the impact of definitive radiation on the survival of HNACC patients without distant metastases, aiming to uncover its nuanced pros and cons.