Hotspots of genetic change in Yersinia pestis.

The relative contributions of mutation rate variation, selection, and recombination in shaping genomic variation in bacterial populations remain poorly understood. Here we analyze 3318 Yersinia pestis genomes, spanning nearly a century and including 2336 newly sequenced strains, to shed light on the patterns of genetic diversity and variation distribution at the population level. We identify 45 genomic regions ("hot regions", HRs) that, although comprising a minor fraction of the genome, are hotbeds of genetic variation.

Co-culture of natural killer cells and tumor spheroids on a heterogeneous multilayer paper stack.

Multilayer paper-based cell culture, as an in vitro three-dimensional (3D) cell culture method, has been frequently used to research drug bioavailability, therapeutic efficacy, and dose-limiting toxicity in malignant tumors. This paper proposes a heterogenous multilayer paper stacking co-culture system to establish a model of natural killer (NK) cells moving through the endothelium layer and attacking tumor spheroids. This system consists of three layers: a bottom tumor-spheroid layer, a middle invasion layer, and a top endothelium layer.

Effect of adding heparin to parenteral nutrition on catheter intraluminal obstruction based on scanning electron microscopy in preterm neonates: A non-inferiority, randomized controlled trial.

Objectives: This study aimed to assess the need for adding heparin to parenteral nutrition (PN) on reducing catheter intraluminal obstruction based on scanning electron microscopy (SEM) of peripherally inserted central catheter (PICC) in preterm neonates.

Methods: In this randomized controlled blinded non-inferiority trial, neonates with gestational age <32 weeks requiring PICC to receive PN were enrolled and randomly divided into two groups. In the heparin group, 0.

Controllable Self-Assembly of V═O Metalloradical Complex with Intramolecular Charge Transfer for Enhanced NIR-II Fluorescence Imaging-Guided Photothermal Therapy.

Near-infrared second region (NIR-II) fluorescence imaging provides enhanced tissue penetration, achieving efficient NIR-II fluorescence and photoacoustic imaging (PA)-guided photothermal therapy (PTT) all in one material remains a challenging yet promising approach in cancer treatment. Herein, open-shell V═O metalloradical complex (VONc) is self-assembled into VONc nanospheres (VONc NPs). VONc NPs exhibit light absorption from 300 to 1400 nm, fluorescence spectra ranging from 900 to 1400 nm, and a distinct fluorescence signal even at 1550 nm.

Tolerability, safety, and pharmacokinetics of GR1603 injection in healthy subjects: a randomized, double-blind, placebo-controlled single-dose escalation clinical trial.

Background: GR1603 is a monoclonal antibody targeting the type I interferon receptor. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and pharmacodynamics of GR1603 in healthy volunteers.

Methods: Healthy adults (≥18 years old) were enrolled in a placebo control, dose-escalation Phase I clinical trial receiving a single injectable dose of GR1603.

The pharmacokinetics, pharmacodynamics and tolerability of SHR6508 in chinese healthy subjects: a randomized, placebo-controlled, double-blind, single-dose and dose-escalation phase I trial.

This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of SHR6508 injection, a new calcimimetic agent, in healthy Chinese subjects following single dose. This study utilized a placebo-controlled, single-dose, and dose-escalation design with four dose groups (0.5 mg, 2.

Five Unreported Ketone Compounds-Penicrustones A-E-From the Endophytic Fungus .

Five unreported ketone compounds-penicrustones A-E-were isolated from the solid fermentation of the endophytic fungus . Their structures were elucidated on the basis of extensive spectroscopic analysis. Their absolute configurations were determined via ECD calculations and single-crystal X-Ray crystallography.

Synthesis of Indol-3-yl Morpholino Derivatives Containing a Hydrazone Moiety as Potential Antiplant Virus Agents.

A series of indol-3-yl morpholino derivatives containing a hydrazone moiety were designed and synthesized using indole-3-carboxylic acid as the starting material. The antiviral activities of the synthesized compounds were systematically evaluated. Compound , optimized using the comparative molecular field analysis (CoMFA) model, exhibited the most potent inhibitory activity against Tobacco mosaic virus (TMV) in vivo with a 50% effective concentration (EC) value of 69.

Topotactic Reduction-Induced Stabilization of β-LaMoO Phase: Structure, Static Oxygen Disorder, and Electrical Properties.

LaMoO is acknowledged as an exceptional oxide ion conductor. It undergoes a reversible phase transition around 580 °C from the nonconductive low-temperature monoclinic α-LaMoO phase to the highly conductive high-temperature cubic β-LaMoO phase. In addition, LaMoO demonstrates complex chemistry under reducing conditions.

Artificial intelligence in predicting pathogenic microorganisms' antimicrobial resistance: challenges, progress, and prospects.

The issue of antimicrobial resistance (AMR) in pathogenic microorganisms has emerged as a global public health crisis, posing a significant threat to the modern healthcare system. The advent of Artificial Intelligence (AI) and Machine Learning (ML) technologies has brought about revolutionary changes in this field. These advanced computational methods are capable of processing and analyzing large-scale biomedical data, thereby uncovering complex patterns and mechanisms behind the development of resistance.

A collagenase-decorated Cu-based nanotheranostics: remodeling extracellular matrix for optimizing cuproptosis and MRI in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), characterized by a dense extracellular matrix (ECM), presents significant therapeutic challenges due to its poor prognosis and high resistance to chemotherapy. Current chemodrugs and diagnostic agents largely fail to cross the barrier posed by the ECM, which severely limits the PDAC theranostics. This study introduces a novel theranostic strategy using thioether-hybridized hollow mesoporous organosilica nanoparticles (dsMNs) for the co-delivery of copper (Cu) and disulfiram (DSF), aiming to induce cuproptosis in PDAC cells.

Effectiveness and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Late-Presenting People With HIV-1 Infection.

Background: The efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) have been demonstrated in treatment-naive clinical trials. However, real-world evidence for this regimen in late-presenting patients with HIV-1 (PWH) is lacking. We investigated the virologic and safety outcomes of BIC/FTC/TAF in late-presenting PWH.

Synthesis of Functionalized Cycloheptadienones Starting from Phenols and Using a Rhodium/Boron Asymmetric Catalytic System.

Skeletal editing offers a unique route to assemble complex architectures from simple feedstocks that are otherwise difficult to obtain. However, the asymmetric version of skeletal editing has not been widely studied. Herein, we present a modular rhodium/boron asymmetric catalytic system that enables ring-expansion of phenols with cyclopropenes to synthesize highly functionalized cycloheptadienones in excellent chemo- and regioselectivities.

BaTiWO: An Oxygen- and B-Site-Deficient 9R Hexagonal Perovskite Exhibiting Triple Conduction.

The hexagonal perovskite derivatives BaM'M″O featuring a hybrid structure composed of 9R hexagonal perovskite and palmierite structure motifs exhibit significant oxide ionic conductivity due to the highly disordered oxide-ion and M-cation sublattices. Herein, we report the structure and electrical properties of the perovskite BaTiWO. Three-dimensional (3D) electron diffraction (ED), neutron powder diffraction (NPD), and neutron pair distribution functions (nPDF) revealed a 9R hexagonal perovskite structure for BaTiWO with fully occupied central M2 sites, partially occupied outer M1 sites, and oxygen-deficient cubic c-BaO sublayers.

Effect of rhizosphere soil microbial communities and environmental factors on growth and the active ingredients of Angelica sinensis in Gansu Province, China.

The growth and accumulation of active ingredients of Angelica sinensis were affected by rhizosphere soil microbial communities and soil environmental factors. However, the correlationship between growth and active ingredients and soil biotic and abiotic factors is still unclear. This study explored rhizosphere soil microbial community structures, soil physicochemical properties, enzyme activities, and their effects on the growth and active ingredient contents of A.

HIF1A/PCDH7 axis mediates fatty acid synthesis and metabolism to inhibit lung adenocarcinoma anoikis.

Background: Aberrantly expressed PCDH7 participates in the malignant progression of many cancers. PCDH7 has been newly discovered as a risk factor in lung cancer, but its functional study in lung adenocarcinoma (LUAD) has not been conducted yet. This study aimed to investigate the functional role of PCDH7 in LUAD.

Diminished ovarian reserve associates with pregnancy and birth outcomes after IVF: a retrospective cohort study.

Antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) are currently the most sensitive and reliable markers of ovarian reserve, but the role of AFC and AMH, as prognosis markers of diminished ovarian reserve (DOR), in pregnancy outcomes after embryo transfer (ET) have been inconsistent. A retrospective cohort study was conducted in a university-affiliated hospital. A total of 4599 women who received their first IVF treatment between January 2012 and December 2019 were included.

The structure elucidation, anti-aging and hypoglycemic effects of an O-acetyl mannoglucan from the bulbs of Lanzhou lily.

An O-acetyl mannoglucan (BHP-1) from Lanzhou lily bulbs was structurally elucidated using partial acid hydrolysis, GC-MS, and 2D NMR techniques (COSY, NOESY, HSQC and HMBC) built on prior research, revealing a backbone of -α-D-(1 → 4)-Glcp-β-D-(1 → 4)-Manp- with the most potential side chains -α-D-(1 → 4)-Glcp-β-D-(1 → 4)-Manp-α-D-(1 → 4)-Glcp-α-D-(1 → Glcp- and -α-D-(1 → 4)-Glcp-β-D-(1 → 4)-Manp-α-D-(1 → Glcp-, attached to O-2 and O-3 of glucose and mannose residues, and featuring O-acetyl groups at O-2 or O-3 position of mannose. The terminal residue was α-D-(1 → Glcp. BHP-1 demonstrated anti-aging and hypoglycemic effects, as assessed by C.