Body Mass Index mediates the relationship between estimated glucose disposal rate and gallstones.

This study examined the relationship between gallstones and estimated glucose disposal rate (eGDR) in people in the United States and the possible mediating function of body mass index (BMI). Data came from the National Health and Nutrition Examination Survey (NHANES), conducted between 2017 and March 2020. Logistic regression, subgroup analysis, smoothed curve fitting, and causal mediation studies were among the statistical techniques used to examine the participant data.

Molecular architecture of human LYCHOS involved in lysosomal cholesterol signaling.

Lysosomal membrane protein LYCHOS (lysosomal cholesterol signaling) translates cholesterol abundance to mammalian target of rapamycin activation. Here we report the 2.11-Å structure of human LYCHOS, revealing a unique fusion architecture comprising a G-protein-coupled receptor (GPCR)-like domain and a transporter domain that mediates homodimer assembly.

Topographic Axes of Wiring Space Converge to Genetic Topography in Shaping Human Cortical Layout.

Genetic information is involved in the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogeneous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles, revealing the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across cortex.

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.

Advances in the relationship of immune checkpoint inhibitors and DNA damage repair.

Cancer immunotherapy, alongside surgery, radiation therapy, and chemotherapy, has emerged as a key treatment modality. Immune checkpoint inhibitors (ICIs) represent a promising immunotherapy that plays a critical role in the management of various solid tumors. However, the limited efficacy of ICI monotherapy and the development of primary or secondary resistance to combination therapy remain a challenge.

Endogenous hydrogen sulfide persulfidates endothelin type A receptor to inhibit pulmonary arterial smooth muscle cell proliferation.

Background: The binding of endothelin-1 (ET-1) to endothelin type A receptor (ETAR) performs a critical action in pulmonary arterial smooth muscle cell (PASMC) proliferation leading to pulmonary vascular structural remodeling. More evidence showed that cystathionine γ-lyase (CSE)-catalyzed endogenous hydrogen sulfide (HS) was involved in the pathogenesis of cardiovascular diseases. In this study, we aimed to explore the effect of endogenous HS/CSE pathway on the ET-1/ETAR binding and its underlying mechanisms in the cellular and animal models of PASMC proliferation.

Effect of trilaciclib administered before chemotherapy in patients with extensive-stage small-cell lung cancer: A pooled analysis of four randomized studies.

Background: Trilaciclib is a transient cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that reduces the incidence of chemotherapy-induced myelosuppression (CIM). In this pooled analysis, we evaluated the multilineage myeloprotection, antitumor efficacy, and safety of trilaciclib treatment in patients with extensive-stage small-cell lung cancer (ES-SCLC). Moreover, myeloprotection effect in 1 L, 2 L/3 L population and effect by risk category were explored.

Chemical characterization of Siraitia grosvenorii granules and their efficacy and mechanism of action on PM2.5-induced acute lung injury.

This study aimed to investigate the potential protective properties of a traditional Chinese medicine (TCM) herbal product, Siraitia grosvenorii granules (SGG) against PM2.5-induced lung injury, as well as their active constituents and underlying mechanisms. The chemical composition of SGG, such as wogonin (MOL000173), luteolin (MOL000006), nobiletin (MOL005828), naringenin (MOL004328), acacetin (MOL001689), were identified via ultra-high-performance liquid chromatography-Q Exactive (UHPLC-QE) Orbitrap/MS.

Deep Equilibrium Unfolding Learning for Noise Estimation and Removal in Optical Molecular Imaging.

In clinical optical molecular imaging, the need for real-time high frame rates and low excitation doses to ensure patient safety inherently increases susceptibility to detection noise. Faced with the challenge of image degradation caused by severe noise, image denoising is essential for mitigating the trade-off between acquisition cost and image quality. However, prevailing deep learning methods exhibit uncontrollable and suboptimal performance with limited interpretability, primarily due to neglecting underlying physical model and frequency information.

Sensitive and Deep Coverage Phosphoproteome Detection Method Reveals Spleen as a More Sensitive Organ than Liver in Early Detection of Liver Fibrosis-Related Signaling Protein Dysregulation.

Although cathepsin S is transported from the spleen to the liver, where it cleaves collagen XVIII to produce endostatin and plays a critical role in the onset of early liver fibrosis, the relationship between liver fibrosis and spleen function remains underexplored. Given the roles of phosphorylation in disease, understanding its regulatory mechanism in early liver fibrosis is crucial. Despite advances in mass spectrometry enhancing phosphoproteomics, its application is limited by small clinical samples and subtle protein changes.

Squamocin Suppresses Tumor Growth through Triggering an Endoplasmic Reticulum Stress-Associated Degradation of EZH2/MYC Axis.

Despite substantial advances in the antitumor effects of annonaceous acetogenins (ACGs), the absence of a defined biological action mechanism remains a major barrier to their clinical application. Here, it is found that squamocin effectively depletes both EZH2 and MYC in multiple cancer cell lines, including head and neck squamous cell carcinoma, and gastric and colorectal cancer, demonstrating potent efficacy in suppressing these in vivo tumor models. Through the combination of surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and cellular thermal shift assay (CETSA), heat shock protein 90α (HSP90α) is identified as the direct binding target of squamocin.

Synthesis of Unprotected Racemic Tryptophan Derivatives Using Gramine via Nickel(II) Complex.

A chemical method for the preparation of nonprotected tryptophan via nickel(II) complexes under simple operating conditions was established. The carefully designed nickel(II) glycinates are inexpensive and can be quantitatively recovered releasing the target tryptophans in high yield. The method has a wide range of synthesis generality, allowing the preparation of various substituted tryptophans.

Oral iron sulfide prevents acute alcohol intoxication by initiating the endogenous multienzymatic antioxidant defense system.

Acute alcohol intoxication could cause multiorgan damage, including nervous, digestive, and cardiovascular systems, and in particular, irreversible damage to the brain and liver. Emerging studies have revealed that the endogenous multienzymatic antioxidant defense system (MEAODS) plays a central role in preventing oxidative stress and other toxicological compounds produced by alcohol. However, few available drugs could quickly regulate MEAODS.

An expanding universe of mutational signatures and its rapid evolution in single-stranded RNA viruses.

The study of mutational processes in somatic genomes has gained recent momentum, uncovering a wide array of endogenous and exogenous factors associated with somatic changes. However, the overall landscape of mutational processes in germline mutations across the tree of life and associated evolutionary driving forces are rather unclear. In this study, we analyzed mutational processes in single-stranded RNA (ssRNA) viruses which are known to jump between different hosts with divergent exogenous environments.

Deciphering transcription activity of mammalian early embryos unveils on/off of zygotic genome activation by protein translation/degradation.

Quantification of transcription activities in mammalian preimplantation embryos is challenging due to a huge amount of maternally stored transcripts and paucity of research materials. Here, we investigate genome-wide transcription activities of mouse and human preimplantation embryos by quantifying elongating RNA polymerase II. Two transcriptional waves are identified in early mouse embryos, with summits at the 2-cell and 8-cell stages.

Advances in moyamoya disease: pathogenesis, diagnosis, and therapeutic interventions.

Moyamoya disease (MMD) is a type of cerebrovascular disease characterized by occlusion of the distal end of the internal carotid artery and the formation of collateral blood vessels. Over the past 20 years, the landscape of research on MMD has significantly transformed. In this review, we provide insights into the pathogenesis, diagnosis, and therapeutic interventions in MMD.

The therapeutic potential of Honeysuckle in cardiovascular disease: an anti-inflammatory intervention strategy.

Honeysuckle is a conventional Chinese medicine with several therapeutic applications. With the advancement of modern scientific technologies, Honeysuckle's pharmacological effects and medicinal properties have been investigated more thoroughly. Studies demonstrate that the bioactive compounds in Honeysuckle possess anti-inflammatory effects via several mechanisms, protecting the cardiovascular system.

Survival outcomes, multidimensional prediction and subsequent therapy in patients with hormone receptor-positive advanced breast cancer receiving palbociclib: a real-world analysis.

Background: To date, the overall survival (OS) of hormone receptor-positive advanced breast cancer (ABC) treated with palbociclib has not been reported in Chinese patients. It still remains unclear what kind of patients may benefit in OS from palbociclib treatment and what the optimal sequential antineoplastic regimen is for those progressing on palbociclib. Therefore, we aimed to investigate the OS outcome of ABC patients receiving palbociclib, establish a predictive model to identify the potential candidates who may benefit from palbociclib and explore the ideal subsequent treatment strategy after palbociclib.

Hemodynamic Evaluation of Intra-Aortic Dual-Balloon Pump Based on Fluid-Structure Interaction.

The intra-aortic balloon pump (IABP) is a widely-used mechanical circulatory support device that enhances hemodynamics in patients with heart conditions. Although the IABP is a common clinical tool, its effectiveness in enhancing outcomes for patients with acute myocardial infarction and cardiogenic shock remains disputed. This study aimed to assess the effectiveness of intra-aortic dual-balloon pump (IADBP) and its impact on aortic hemodynamics compared with an IABP.

Microfluidic Approach for Enhanced Paeoniflorin Transdermal Delivery: A Comparative Study on Different Chips and Mixing Dynamics.

Paeoniflorin is a natural pharmaceutical ingredient with a widely biological activity. However, as a hydrophilic drug, the problem of low transdermal rate limits its clinical application. To overcome this shortage, LUVs were used as biocompatible carriers of paeoniflorin in this study.

Deep learning-aided diagnosis of acute abdominal aortic dissection by ultrasound images.

Purpose: Acute abdominal aortic dissection (AD) is a serious disease. Early detection based on ultrasound (US) can improve the prognosis of AD, especially in emergency settings. We explored the ability of deep learning (DL) to diagnose abdominal AD in US images, which may help the diagnosis of AD by novice radiologists or non-professionals.