Functionally active modulators targeting the LRRK2 WD40 repeat domain identified by FRASE-bot in CACHE Challenge #1.

Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenges emerged as real-life stress tests for computational hit-finding strategies. In CACHE Challenge #1, 23 participants contributed their original workflows to identify small-molecule ligands for the WD40 repeat (WDR) of LRRK2, a promising Parkinson's target. We applied the FRASE-based hit-finding robot (FRASE-bot), a platform for interaction-based screening allowing a drastic reduction of the explorable chemical space and a concurrent detection of putative ligand-binding sites.

Genetic and clinical spectrum of steroid-resistant nephrotic syndrome with nuclear pore gene mutation.

Background: Steroid-resistant nephrotic syndrome (SRNS) is insensitive to steroid therapy and overwhelmingly progresses to kidney failure (KF), the known pathogenic genes of which include key subunits of the nuclear pore complex (NPC), a less-recognized contributor to glomerular podocyte injury.

Methods: After analyzing their clinical characterizations and obtaining parental consent, whole-exome sequencing (WES) was performed on patients with SRNS. Several nucleoporin (NUP) biallelic pathogenic variants were identified and further analyzed by cDNA-PCR sequencing from white cells of peripheral blood, minigene assay, immunohistochemical (IHC) staining, and electron microscopy (EM) ultrastructure observation of kidney biopsy, as well as multiple in silico prediction tools, including 3D protein modeling.

Characterizing Surface Deformation of the Earthquake-Induced Daguangbao Landslide by Combining Satellite- and Ground-Based InSAR.

The Daguangbao landslide (DGBL), triggered by the 2008 Wenchuan earthquake, is a rare instance of super-giant landslides globally. The post-earthquake evolution of the DGBL has garnered significant attention in recent years; however, its deformation patterns remain poorly characterized owing to the complex local topography. In this study, we present the first observations of the surface dynamics of DGBL by integrating satellite- and ground-based InSAR data complemented by kinematic interpretation using a LiDAR-derived Digital Surface Model (DSM).

A cross-sectional study on exposure to secondhand smoke in indoor public places and attitudes of residents towards the smoke control ordinance in public places.

Introduction: Secondhand smoke (SHS) exposure is a serious public health problem. This study aims to collect data on tobacco control since the implementation of the new version of the Smoke Control Ordinance in Public Places of Hangzhou (the Ordinance), combined with questionnaire surveys to understand the SHS exposure situation in public places, relevant knowledge and attitudes of residents in Hangzhou.

Methods: We used data from a population-based tobacco control survey of 2746 adults aged 15-75 years conducted in Hangzhou, Zhejiang Province in March 2023.

Automatic Pavlov ratio measurement method based on spinal landmarks identification by a deep-learning model.

Background: Cervical canal stenosis is one of the important pathogenic factors of cervical spondylosis. The accuracy of the Pavlov ratio measurement is crucial for the diagnosis and treatment of cervical spinal stenosis. Manual measurement is influenced by observer variability, accompanied by its inefficiency, which affects clinical evaluation.

Effect of sacubitril/valsartan in heart failure with preserved ejection fraction across the age spectrum in PARAGON-HF.

Aims: To evaluate clinical outcomes, echocardiographic features, and the efficacy and safety of sacubitril/valsartan compared to valsartan across age groups in the PARAGON-HF trial.

Methods And Results: A total of 4796 participants ≥50 years of age with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) ≥45% were divided into three age groups: <65 years (n = 825), 65-74 years (n = 1772), and ≥75 years (n = 2199). Echocardiograms of 1097 patients were analysed in a standardized fashion at a core imaging laboratory.

Impact of low-dose free chlorine on the conjugative transfer of antibiotic resistance genes in wastewater effluents: Identifying key environmental factors for predictive modeling.

Reclaimed water disinfection results in the coexistence of antibiotic resistance genes (ARGs) and low-dose free chlorine in receiving environments. However, the impact of low-dose free chlorine on ARGs conjugative transfer and the key factors influencing the transfer under complex environmental conditions remain unclear, hindering the establishment of an effective monitoring system for resistance pollution in reclaimed water. This study investigated ARGs conjugative transfer under the influence of free chlorine at environmentally relevant concentrations and key interactive factors using machine learning models.

π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

[Research progress on pathogenic germline mutations in malignant tumors].

Malignant tumors are closely related to various genetic and environmental factors. Pathogenic germline gene mutations play a key role in the occurrence and development of some malignant tumors. Some germline mutations can increase the risk of malignant tumors.

Preparation of diacylglycerol by lipase-catalyzed glycerolysis in the presence of polar adsorption materials.

Diacylglycerol (DAG) is a functional oil used extensively in various industries. Glycerolysis of a natural oil with glycerol was widely employed for DAG preparation. Numerous studies have demonstrated that glycerol in the reaction affects lipase performance.

The matrix stiffness is increased in the eutopic endometrium of adenomyosis patients: a study based on atomic force microscopy and histochemistry.

Previous ultrasound studies suggest that patients with adenomyosis (AM) exhibit increased uterine cavity stiffness, although direct evidence regarding extracellular matrix (ECM) content and its specific impact on endometrial stiffness remains limited. This study utilized atomic force microscopy to directly measure endometrial stiffness and collagen morphology, enabling a detailed analysis of the endometrium's mechanical properties: through this approach, we established direct evidence of increased endometrial stiffness and fibrosis in patients with AM. Endometrial specimens were also stained with Picrosirius red or Masson's trichrome to quantify fibrosis, and additional analyses assessed α-SMA and Ki-67 expression.

Effect of ultrasound combined with plasma protein treatment on the structure, physicochemical and rheological properties of myofibrillar protein.

This study aimed to investigate the effect of ultrasound combined with plasma protein (UPP) treatment on the structure, physicochemical and rheological properties of myofibrillar protein (MP). The results indicated that the UPP group caused changes in the secondary structure, increased fluorescence intensity and enhanced surface hydrophobicity of MP. Then, UPP significantly decreased the content of free and total sulfhydryl group, and high molecular weight protein contents were observed in MP.

Ultra-Processed Foods and the Impact on Cardiometabolic Health: The Role of Diet Quality.

The consumption of ultra-processed foods (UPFs) has surged globally, raising significant public health concerns due to their associations with a range of adverse health outcomes. This review aims to elucidate potential health impacts of UPF intake and underscore the importance of considering diet quality when interpreting study findings. UPF group, as classified by the Nova system based on the extent of industrial processing, contains numerous individual food items with a wide spectrum of nutrient profiles, as well as differential quality as reflected by their potential health effects.

Proton-Mediated Dynamic Nestling of DNA Payloads Within Size-Matched MOFs Nanochannels for Smart Intracellular Delivery.

With sequence-programmable biological functions and excellent biocompatibility, synthetic functional DNA holds great promise for various biological applications. However, it remains a challenge to simultaneously retain their biological functions while protecting these fragile oligonucleotides from the degradation by nucleases abundant in biological circumstances. Herein, a smart delivery system for functional DNA payloads is developed based on proton-mediated dynamic nestling of cytosine-rich DNA moieties within the precisely size-matched nanochannels of highly crystalline metal-organic frameworks (MOFs): At neutral pH, cytosine-rich DNA strands exhibit a flexible single-stranded state and can be accommodated by MOFs nanochannels with a size of ca.

Azithromycin inhibits the intracellular persistence of Acinetobacter baumannii by inducing host cell autophagy in human bronchial epithelial cells.

The invasion of host cells by bacteria, leading to intracellular infections, is a major cause of infection recurrence. Drug-resistant Acinetobacter baumannii (A. baumannii) is one of the most challenging public health issues worldwide, with very limited clinical treatment options available.

microRNA-18a-5p promotes vascular smooth muscle cell phenotypic switch by targeting Notch2 as therapeutic targets in vein grafts restenosis.

Vascular smooth muscle cells (VSMCs) phenotype switching plays a crucial role in vein graft restenosis following coronary artery bypass grafting (CABG) surgery. To discover novel clinically relevant therapeutic targets for vein graft restenosis after CABG, we therefore investigated whether miRNA-18a-5p mediated phenotype switching plays a critical role in the development of vein graft restenosis. We studied miRNA-18a-5p expression in plasma samples of patients with or without vein graft restenosis at 1, 3 and 5 years after coronary artery bypass graft surgery, and in normal vs.

Foxtail millet bran dietary fibres foster in vitro beneficial gut microbes and metabolites while suppressing pathobionts.

Foxtail millet bran soluble dietary fibre (MBSDF) is a dietary compound with various bioactivities, potentially modulated by the gut microbiota. To elucidate this bioregulatory mechanism, this study focused on the structureal composition and in vitro fermentation characteristics of MBSDF. The results revealed that MBSDF has a molecular weight of 18.

Improving the Gelation Properties of Pea Protein Isolates Using Psyllium Husk Powder: Insight into the Underlying Mechanism.

The industrial application of pea protein is limited due to its poor gelation properties. This study aimed to evaluate the effects of psyllium husk powder (PHP) on improving the rheological, textural, and structural properties of heat-induced pea protein isolate (PPI) gel. Scanning electron microscopy (SEM), intermolecular forces analysis, the quantification of the surface hydrophobicity and free amino groups, and Fourier transform infrared spectroscopy (FTIR) were conducted to reveal the inner structures of PPI-PHP composite gels, conformational changes, and molecular interactions during gelation, thereby clarifying the underlying mechanism.

Single Amine or Guanidine Modification on Norvancomycin and Vancomycin to Overcome Multidrug-Resistance through Augmented Lipid II Binding and Increased Membrane Activity.

Vancomycin and norvancomycin have diminished antibacterial efficacy due to acquired or intrinsic resistance from mutations in the terminal dipeptide of lipid II in Gram-positive bacteria or failure to penetrate into the periplasm in Gram-negative bacteria. Herein, we rationally designed and synthesized a series of vancomycin analogues bearing single amine or guanidine functionality, altering various linkers and modification sites, to combat the resistance. Extensive antibacterial screening was performed to delineate a comprehensive SAR.