Acquired bla carried by a conjugative transposon or duplicated intrinsic bla mediates cefiderocol resistance in Elizabethkingia anophelis clinical isolates.

Objectives: Elizabethkingia spp. are resistant to multiple antibiotics. This study aimed to determine in vitro and in vivo activities of cefiderocol against Elizabethkingia spp.

Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia.

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges.

The individual contributions of blaB, blaGOB and blaCME on MICs of β-lactams in Elizabethkingia anophelis.

Background: The blaB, blaGOB and blaCME genes are thought to confer β-lactam resistance to Elizabethkingia anophelis, based on experiments conducted primarily on Escherichia coli.

Objectives: To determine the individual contributions of β-lactamase genes to increased MICs in E. anophelis and to assess their impact on the in vivo efficacy of carbapenem therapy.

Decrypting orphan GPCR drug discovery via multitask learning.

The drug discovery of G protein-coupled receptors (GPCRs) superfamily using computational models is often limited by the availability of protein three-dimensional (3D) structures and chemicals with experimentally measured bioactivities. Orphan GPCRs without known ligands further complicate the process. To enable drug discovery for human orphan GPCRs, multitask models were proposed for predicting half maximal effective concentrations (EC) of the pairs of chemicals and GPCRs.

Visualizing the DNA repair process by a photolyase at atomic resolution.

Photolyases, a ubiquitous class of flavoproteins, use blue light to repair DNA photolesions. In this work, we determined the structural mechanism of the photolyase-catalyzed repair of a cyclobutane pyrimidine dimer (CPD) lesion using time-resolved serial femtosecond crystallography (TR-SFX). We obtained 18 snapshots that show time-dependent changes in four reaction loci.

Analysis of structure-activity relationship of indol-3-yl-N-phenylcarbamic amides as potent STING inhibitors.

A structure-activity relationship (SAR) study of stimulator of interferon gene (STING) inhibition was performed using a series of indol-3-yl-N-phenylcarbamic amides and indol-2-yl-N-phenylcarbamic amides. Among these analogs, compounds 10, 13, 15, 19, and 21 inhibited the phosphorylation of STING and interferon regulatory factor 3 (IRF3) to a greater extent than the reference compound, H-151. All five analogs showed stronger STING inhibition than H-151 on the 2',3'-cyclic GMP-AMP-induced expression of interferon regulatory factors (IRFs) in a STING knock-in THP-1 reporter cell line.

Marine diterpenoid targets STING palmitoylation in mammalian cells.

Natural products are important sources of therapeutic agents and useful drug discovery tools. The fused macrocycles and multiple stereocenters of briarane-type diterpenoids pose a major challenge to total synthesis and efforts to characterize their biological activities. Harnessing a scalable source of excavatolide B (excB) from cultured soft coral Briareum stechei, we generated analogs by late-stage diversification and performed structure-activity analysis, which was critical for the development of functional excB probes.

A chromosome-scale genome assembly of provides new insights into the evolution and adaptation of Fagaceae species.

Fagaceae species dominate forests and shrublands throughout the Northern Hemisphere, and have been used as models to investigate the processes and mechanisms of adaptation and speciation. Compared with the well-studied genus , genomic data is limited for the tropical-subtropical genus . is an ecologically and economically valuable species with a wide distribution in the evergreen broad-leaved forests of tropical-subtropical Asia.

 (Commelinaceae), a new species from Guangdong, China.

(Commelinaceae), a remarkable new species from Mount Danxia, Guangdong Province, China, is described and illustrated. This species is similar to in inflorescences and flowers but readily distinguishable in its nearly erect stems, larger flowers, and different petal colouration.

Dynamic interaction nursing intervention on functional rehabilitation and self-care ability of patients after aneurysm surgery.

Background: Nursing practices based on the dynamic interaction model have been shown to be superior to generic nursing practices. However, whether this model is effective in patients recovering from intracranial aneurysm surgery is not well studied.

Aim: To investigate the effect of nursing based on a dynamic interaction model on functional rehabilitation of patients after aneurysm surgery.

Serial crystallography captures dynamic control of sequential electron and proton transfer events in a flavoenzyme.

Flavin coenzymes are universally found in biological redox reactions. DNA photolyases, with their flavin chromophore (FAD), utilize blue light for DNA repair and photoreduction. The latter process involves two single-electron transfers to FAD with an intermittent protonation step to prime the enzyme active for DNA repair.

Community-Based Screening for Hepatitis B and C Infectivity Using Two Quantitative Antigens to Identify Endemic Townships.

Screening and linkage to care are essential to achieve viral hepatitis elimination before 2030. The accurate identification of endemic areas is important for controlling diseases with geographic aggregation. Viral activity drives prognosis of chronic hepatitis B and hepatitis C virus infection.

and comparison of eravacycline- and tigecycline-based combination therapies for tigecycline-resistant .

Several antimicrobial combination therapies are used to treat multiple drug resistant (MDR) and extensively drug resistant (XDR) infections. A novel antibiotic, eravacycline, shows a higher potency than tigecycline. The efficacies of eravacycline-based therapies have not yet been evaluated.

Outcomes of hepatitis B immunoglobulin and hepatitis B vaccination in high-risk newborns born to HBeAg-positive mothers.

Background: To evaluate the protective efficacy of a hepatitis B (HB) vaccination program in Taiwan among high-risk children.

Methods: Children born to HBeAg-positive mothers from 2001 to 2010 were invited back. Blood samples for hepatitis B virus (HBV) seromarkers were taken and the children underwent hepatobiliary ultrasonography.

Village-to-village screening for hepatitis B and C using quantitative HBsAg and anti-HCV testing with reflex HCV core antigen tests in the remote communities of a resource-rich setting: a population-based prospective cohort study.

Objectives: Community-based screening for hepatitis B virus (HBV) and hepatitis C virus (HCV) is essential for hepatitis elimination. This study attempted to increase screening accessibility and efficacy by using alternative tools.

Design: Population-based prospective cohort study.

In vitro activity of imipenem/relebactam, meropenem/vaborbactam, ceftazidime/avibactam, cefepime/zidebactam and other novel antibiotics against imipenem-non-susceptible Gram-negative bacilli from Taiwan.

Objectives: To investigate the susceptibility of imipenem-non-susceptible Escherichia coli (INS-EC), Klebsiella pneumoniae (INS-KP), Acinetobacter baumannii (INS-AB) and Pseudomonas aeruginosa (INS-PA) to novel antibiotics.

Methods: MICs were determined using the broth microdilution method. Carbapenemase and ESBL phenotypic testing and PCR for genes encoding ESBLs, AmpCs and carbapenemases were performed.

Vibrio cholerae biofilm scaffolding protein RbmA shows an intrinsic, phosphate-dependent autoproteolysis activity.

Vibrio cholerae is the causative agent of the diarrheal disease cholera, for which biofilm communities are considered to be environmental reservoirs. In endemic regions, and after algal blooms, which may result from phosphate enrichment following agricultural runoff, the bacterium is released from biofilms resulting in seasonal disease outbreaks. However, the molecular mechanism by which V.

Susceptibility of Elizabethkingia spp. to commonly tested and novel antibiotics and concordance between broth microdilution and automated testing methods.

Objectives: We aimed to determine susceptibilities of Elizabethkingia spp. to 25 commonly tested and 8 novel antibiotics, and to compare the performance of different susceptibility testing methods.

Methods: Clinical isolates of Elizabethkingia spp.

Clinical and molecular characterization of Acinetobacter seifertii in Taiwan.

Objectives: Acinetobacter seifertii, a new member of the Acinetobacter baumannii group, has emerged as a cause of severe infections in humans. We investigated the clinical and molecular characteristics of A. seifertii.

Feasibility of anti-HCV reflex HCV Ag screening strategy in an HCV endemic community.

Background/purpose: The HCV core antigen (HCV Ag) assay displays high sensitivity and strong correlation with HCV RNA. However, the feasibility of anti-HCV reflex HCV Ag screening in a community-wide setting is rarely discussed.

Methods: We performed a two-phase community-based hepatitis C screen in an HCV-prone area of central Taiwan.

Usefulness of quantitative hepatitis B surface antigen testing in hepatitis B community-based screening.

Background/purpose: Low viral load (LVL) of hepatitis B virus (HBV) is a predictor of chronic HBV infection. However, the usefulness of quantitative hepatitis B surface antigen (qHBsAg) in predicting LVL in community-based screening has not been well studied. We aimed to measure the prevalence of LVL in HBV carriers and validate the efficacy of qHBsAg in predicting LVL.

Association between topical beta-blockers and risks of cardiovascular and respiratory disease in patients with glaucoma: a retrospective cohort study.

Objective: To determine if topical beta-blocker use is associated with increased risks of cardiovascular and respiratory diseases in patients with glaucoma.

Setting: A retrospective cohort analysis was conducted using the database from Taiwan's National Health Insurance programme.

Participants: In total, 12 336 newly diagnosed patients with glaucoma from January 2000 to December 2010 were included.