Bayesian Effect Size Ranking to Prioritise Genetic Risk Variants in Common Diseases for Follow-Up Studies.

Biological datasets often consist of thousands or millions of variables, e.g. genetic variants or biomarkers, and when sample sizes are large it is common to find many associated with an outcome of interest, for example, disease risk in a GWAS, at high levels of statistical significance, but with very small effects.

Dual Role of Lysosome in Cancer Development and Progression.

Lysosomes are essential intracellular catabolic organelles that contain digestive enzymes involved in the degradation and recycle of damaged proteins, organelles, etc. Thus, they play an important role in various biological processes, including autophagy regulation, ion homeostasis, cell death, cell senescence. A myriad of studies has shown that the dysfunction of lysosome is implicated in human aging and various age-related diseases, including cancer.

Cyclic Diguanylate G-Quadruplex Inducer-Quorum Sensing Inhibitor Hybrids as Bifunctional Anti-biofilm and Anti-virulence Agents Against .

The release of virulence factors and biofilm formation by are pivotal drivers of its severe pathogenicity and antibiotic resistance. Based on our prior findings, cyclic di-GMP (c-di-GMP) G-quadruplex inducers are promising biofilm inhibitors and that quorum sensing systems are central regulators of virulence, we aimed to design and synthesize c-di-GMP G-quadruplex inducer-quorum sensing inhibitor hybrids. These hybrids were envisioned as bifunctional agents with both antibiofilm and antivirulence capabilities.

Hybrids of 3-Hydroxypyridin-4(1)-ones and Long-Chain 4-Aminoquinolines as Potent Biofilm Inhibitors of Potentiate Tobramycin and Polymyxin B Activity.

The biofilm formation of involves multiple complex regulatory pathways; thus, blocking a single pathway is unlikely to achieve the desired antibiofilm efficacy. Herein, a series of hybrids of 3-hydroxypyridin-4(1)-ones and long-chain 4-aminoquinolines were synthesized as biofilm inhibitors against based on a multipathway antibiofilm strategy. Comprehensive structure-activity relationship studies identified compound as the most valuable antagonist, which significantly inhibited biofilm formation (IC = 5.

Establishment of a visualized mouse orthotopic xenograft model of nasopharyngeal carcinoma.

Mouse orthotopic xenograft tumor models are commonly employed in studies investigating the mechanisms underlying the development and progression of tumors and their preclinical treatment. However, the unavailability of mature and visualized orthotopic xenograft models of nasopharyngeal carcinoma limits the development of treatment strategies for this cancer. The aim of this study was to provide a simple and reliable method for building an orthotopic xenograft model of nasopharyngeal carcinoma.

 (Agaricales, Agaricomycetes), , and (Dacrymycetales, Dacrymycetes), three new species from Yunnan Province, southwestern China.

Three new species belonging to Basidiomycota from southwestern China are described based on morphological and molecular data. is morphologically characterized by dorsally pseudostipitate, pale orange to brownish orange pileus, excentric to lateral pseudostipe, crowded lamellae, cylindrical-ellipsoid basidiospores 3.0-4.

Realizing Color Transitions for Three Copper (I) Cluster Organic-Inorganic Hybrid Materials by Adjusting Reaction Conditions.

Copper iodide organic-inorganic hybrid materials have been favored by many researchers in the field of solid-state lighting (SSL) due to their structural diversity and optical adjustability. In this paper, three isomeric copper iodide cluster hybrid materials, CuI(L)(1), CuICl(L)(2) and CuI(L)) (3) (L=1-(4-methylpyrimidin-2-yl)-1,4-diazabicyclo[2.2.

BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment.

BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment.

Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo.

The impact of COVID-19 restrictions on motorcycle crashes in Taiwan.

Taiwan is one of the countries with the highest motorcycle per capita globally, and motorcycle crashes are predominant among traffic crashes. This study examines the impact of coronavirus disease 2019 restrictions on motorcycle crashes. We analyzed the trend of motorcycle crashes in Taipei City from 2019 to 2020 using the dataset provided by the Department of Transportation, Taipei City Government, Taiwan.

Cajaninstilbene acid derivatives conjugated with siderophores of 3-hydroxypyridin-4(1H)-ones as novel antibacterial agents against Gram-negative bacteria based on the Trojan horse strategy.

The low permeability of the outer membrane of Gram-negative bacteria is a serious obstacle to the development of new antibiotics against them. Conjugation of antibiotic with siderophore based on the "Trojan horse strategy" is a promising strategy to overcome the outer membrane obstacle. In this study, series of antibacterial agents were designed and synthesized by conjugating the 3-hydroxypyridin-4(1H)-one based siderophores with cajaninstilbene acid (CSA) derivative 4 which shows good activity against Gram-positive bacteria by targeting their cell membranes but is ineffective against Gram-negative bacteria.

A multi-ancestry genome-wide association study in type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease caused by destruction of the pancreatic β-cells. Genome-wide association (GWAS) and fine mapping studies have been conducted mainly in European ancestry (EUR) populations. We performed a multi-ancestry GWAS to identify SNPs and HLA alleles associated with T1D risk and age at onset.

Lysophosphatidic Acid Receptor 3 Activation Is Involved in the Regulation of Ferroptosis.

Ferroptosis, a unique form of programmed cell death trigged by lipid peroxidation and iron accumulation, has been implicated in embryonic erythropoiesis and aging. Our previous research demonstrated that lysophosphatidic acid receptor 3 (LPA) activation mitigated oxidative stress in progeria cells and accelerated the recovery of acute anemia in mice. Given that both processes involve iron metabolism, we hypothesized that LPA activation might mediate cellular ferroptosis.

Implementation of type 1 diabetes genetic risk screening in children in diverse communities: the Virginia PrIMeD project.

Background: Population screening for risk of type 1 diabetes (T1D) has been proposed to identify those with islet autoimmunity (presence of islet autoantibodies). As islet autoantibodies can be transient, screening with a genetic risk score has been proposed as an entry into autoantibody testing.

Methods: Children were recruited from eight general pediatric and specialty clinics across Virginia with diverse community settings.

[Evaluation of the Short-Term Efficacy and Safety of Orelabrutinib Combined with High-Dose Methotrexate in the First-line Treatment of Elderly Patients with High Risk Primary Central Nervous System Lymphoma].

Objective: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients.

Methods: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy.

3-Hydroxypyridin-4(1)-one Derivatives as Quorum Sensing Inhibitors Attenuate Virulence and Reduce Antibiotic Resistance in .

The development of quorum sensing inhibitors capable of decreasing the production of virulence factors is an effective strategy to overcome resistance in due to the less selective pressure exerted on bacteria. In this study, a series of 3-hydroxypyridin-4(1)-one derivatives bearing a 4-aminomethyl-1,2,3-triazole linker were designed and synthesized as antivirulence agents against . The most potent derivative was identified as a selective inhibitor of the system (IC = 3.

Incidence and prevalence of keratoconus in Taiwan during 2000-2018 and their association with the use of corneal topography and tomography.

Purpose: The aim of this study was to determine the age- and sex-specific incidence and prevalence of keratoconus (KC) in Taiwan and explore their association with the use of computerized corneal topography and tomography (TG).

Design: This nationwide retrospective study included the Taiwanese population (N = 27,540,859) from the National Health Insurance Research Database (NHIRD) between 2000 and 2018.

Method: We estimated the incidence of KC by identifying patients with newly diagnosed KC and estimated its prevalence by identifying patients who had the ICD9-CM code 371.

Cyclic Diguanylate G-Quadruplex Inducer-Nitric Oxide Donor Conjugate as a Bifunctional Antibiofilm Agent and Antibacterial Synergist against with a Hyperbiofilm Phenotype.

Antibiotic resistance caused by biofilm formation is a clinical challenge. Nitric oxide (NO) can effectively disperse a mature biofilm and can also synergistically influence the level of cyclic diguanylate (c-di-GMP), a universal secondary messenger that plays an important role in biofilm formation in bacteria. Based on our previous finding that c-di-GMP G-quadruplex inducers are effective biofilm formation inhibitors, we designed and synthesized a c-di-GMP G-quadruplex inducer-NO donor conjugate () as a bifunctional antibiofilm agent after obtaining the c-di-GMP G-quadruplex inducer (), which has an amino group capable of binding to a nitroso group (NO donor).

Design, synthesis and biological evaluation of novel 3-hydroxypyridin-4(1H)-ones based hybrids as Pseudomonas aeruginosa biofilm inhibitors.

Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative pathogenic bacterium, often causative drug-resistance related human infections, given its great capacity to form bioflm. It uses three major quorum sensing (QS) systems, las, rhl, and pqs, to regulate the expression of genes related to virulence and biofilm formation.

3-Hydroxy-pyridin-4(1H)-ones as siderophores mediated delivery of isobavachalcone enhances antibacterial activity against pathogenic Pseudomonas aeruginosa.

The natural prenylated chalcone isobavachalcone (IBC) shows good antibacterial activity against Gram-positive bacteria but is ineffective against Gram-negative bacteria, most likely due to the outer membrane barrier of Gram-negative bacteria. The Trojan horse strategy has been shown to be an effective strategy to overcome the reduction in the permeability of the outer membrane of Gram-negative bacteria. In this study, eight different 3-hydroxy-pyridin-4(1H)-one-isobavachalcone conjugates were designed and synthesized based on the siderophore Trojan horse strategy.