Choline metabolism modulates cyclic-di-GMP signaling and virulence of Pseudomonas aeruginosa in a macrophage infection model.

Background: Bacterial pathogens frequently encounter host-derived metabolites during their colonization and invasion processes, which can serve as nutrients, antimicrobial agents, or signaling molecules for the pathogens. The essential nutrient choline (Cho) is widely known to be utilized by a diverse range of bacteria and may undergo conversion into the disease-associated metabolite trimethylamine (TMA). However, the impact of choline metabolism on bacterial physiology and virulence remains largely unexplored.

Recruitment of the diaphragm and sternocleidomastoid muscle during increasing inspiratory pressure loads in healthy young adults.

Background: Inspiratory muscle training (IMT) is often employed to enhance improvement in inspiratory muscle strength. However, the relationship between inspiratory muscle recruitment patterns and increasing inspiratory load remains unclear. Furthermore, the effect of breathing instructions on diaphragm activity at various inspiratory loads is unknown.

Novel Peptide DR3penA as a Low-Toxicity Antirenal Fibrosis Agent by Suppressing the TGF-β1/miR-212-5p/Low-Density Lipoprotein Receptor Class a Domain Containing 4/Smad Axis.

Renal fibrosis is a complex pathological process that contributes to the development of chronic kidney disease due to various risk factors. Conservative treatment to curb progression without dialysis or renal transplantation is widely applicable, but its effectiveness is limited. Here, the inhibitory effect of the novel peptide DR3penA (DHα-(4-pentenyl)-AlaNPQIR-NH), which was developed by our group, on renal fibrosis was assessed in cells and mice with established fibrosis and fibrosis triggered by transforming growth factor-β1 (TGF-β1), unilateral ureteral obstruction, and repeated low-dose cisplatin.

Azalomycin F4a targets peptidoglycan synthesis of Gram-positive bacteria revealed by high-throughput CRISPRi-seq analysis.

Azalomycin F4a is a promising 36-membered polyhydroxy macrolide that shows antibacterial activity against drug-resistant Gram-positive bacteria, but its exact working mechanism remains to be elusive. Here, we isolated the azalomycin F4a product from a Streptomyces solisilvae and demonstrated its antibacterial activity against Gram-positive pathogens including Streptococcus pneumoniae, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). We further showed that combination of azalomycin F4a with methicillin has an additive antimicrobial effect on MRSA, where the minimal inhibitory concentrations (MIC) of methicillin to MRSA was decreased by 1000-fold in the presence of sublethal concentration of azalomycin F4a.

The Peptide DH-(4-pentenyl)-ANPQIR-NH Exhibits Antifibrotic Activity in Multiple Pulmonary Fibrosis Models Induced by Particulate and Soluble Chemical Fibrogenic Agents.

Interstitial lung diseases (ILDs) are a group of restrictive lung diseases characterized by interstitial inflammation and pulmonary fibrosis. The incidence of ILDs associated with exposure to multiple hazards such as inhaled particles, fibers, and ingested soluble chemicals is increasing yearly, and there are no ideal drugs currently available. Our previous research showed that the novel and low-toxicity peptide DH-(4-pentenyl)-ANPQIR-NH (DR3penA) had a strong antifibrotic effect on a bleomycin-induced murine model.

Do atrophic gastritis and intestinal metaplasia reverse after Helicobacter pylori eradication?

Background: It's still controversial whether Helicobacter pylori (H. pylori) eradication can reverse atrophic gastritis (AG) and intestinal metaplasia (IM). Therefore, we performed a meta-analysis to estimate the effect of H.

The novel peptide DR4penA attenuates the bleomycin- and paraquat-induced pulmonary fibrosis by suppressing the TGF-β/Smad signaling pathway.

Pulmonary fibrosis (PF), which is caused by continuous alveolar epithelial cell injury and abnormal repair, is referred to as a difficult disease of the lung system by the World Health Organization due to its rapid progression, poor prognosis, and high mortality rate. However, there is still a lack of ideal therapeutic strategies. The peptide DR8 (DHNNPQIR-NH ), which is derived from rapeseed, exerted antifibrotic activity in the lung, liver, and kidney in our previous studies.

The usnic acid derivative peziculone targets cell walls of Gram-positive bacteria revealed by high-throughput CRISPRi-seq analysis.

Usnic acid, a representative dibenzofuran metabolite, is known to have antimicrobial properties. However, despite considerable interest as an antimicrobial agent, the mechanism by which usnic acid and its derivatives exert their action is not fully characterized. This article describes the synthesis of peziculone, a 5:1 equilibrium mixture of two inseparable usnic acid derivatives: peziculone A and peziculone B.

The Early Impact of the People-centred Integrated Care on the Hypertension Management in Shenzhen.

Objective: To evaluate the impact of the integrated care in Luohu, China on the hypertension management.

Methods: Hypertensive patients aged 35-74 years were recruited by the cluster-randomized sampling method from Luohu district which adopted integrated care and another district that remained original routine care during October 2018~January 2020, with 1353 and 583 patients from integrated and routine care communities, respectively. Health information, knowledge, attitude, and practice (KAP) towards cardiovascular diseases, pharmaceutical expenditure on hypertension and its comorbidities, and healthcare-related satisfaction were collected by questionnaires, with the expenditure additionally verified by hospitals' billing records database.

Synthesis and Biological Evaluation of Phthalideisoquinoline Derivatives.

A photo and Cu-mediated radical-radical approach enabling the one-step synthesis of the phthalideisoquinoline skeleton has been reported. Under mild reaction conditions, a series of -aryl phthalideisoquinolines containing various substituents were synthesized in moderate to good yields. Bioactivity data demonstrated that a new compound can efficiently inhibit the growth of multiple tumor cell lines with enhancements of more than 10-fold by significantly increasing G/M arrest compared with noscapine.

Facile Entry to Pharmaceutically Important 3-Difluoromethyl-quinoxalin-2-ones Enabled by Visible-Light-Driven Difluoromethylation of Quinoxalin-2-ones.

CFH moiety has a significant potential utility in drug design and discovery, and the incorporation of CFH into biologically active molecules represents an important and efficient strategy for seeking lead compounds and drug candidates. On the other hand, quinoxalin-2-one is of great interest to pharmaceutical chemists as a common skeleton frequently occurring in plenty of natural products and bioactive compounds. Herein, we reported a practical and efficient protocol for the synthesis of 3-CFH-quinoxalin-2-ones.

CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72.

Background: The centrosome is one of the most important non-membranous organelles regulating microtubule organization and progression of cell mitosis. The coiled-coil alpha-helical rod protein 1 (CCHCR1, also known as HCR) gene is considered to be a psoriasis susceptibility gene, and the protein is suggested to be localized to the P-bodies and centrosomes in mammalian cells. However, the exact cellular function of HCR and its potential regulatory role in the centrosomes remain unexplored.

Sufentanil: a risk factor for lactic acidosis in patients after heart valve surgery.

Backgrounds: Hyperlactatemia is a common metabolic disorder after cardiac surgery with cardiopulmonary bypass. Epinephrine use has been identified as a potential cause of increased lactate levels after cardiac surgery. Stress can lead to an increase in catecholamines, mainly epinephrine, in the body.

Stroke volume and cardiac output during 6 minute-walk tests are strong predictors of maximal oxygen uptake in people after stroke.

Background And Objectives: The 6-minute walk test (6MWT) is a field test commonly used to predict peak oxygen consumption (VO2peak) in people after stroke. Inclusion of cardiodynamic variables measured by impedance cardiography (ICG) during a 6MWT has been shown to improve prediction of VO2peak in healthy adults but these data have not been considered in people after stroke. This study investigates whether the prediction of VO2peak can be improved by the inclusion of cardiovascular indices derived by impedance cardiography (ICG) during the 6MWT in people after stroke.

Optimizing acute stroke outcome prediction models: Comparison of generalized regression neural networks and logistic regressions.

Background: Generalized regression neural network (GRNN) and logistic regression (LR) are extensively used in the medical field; however, the better model for predicting stroke outcome has not been established. The primary goal of this study was to compare the accuracies of GRNN and LR models to identify the most optimal model for the prediction of acute stroke outcome, as well as explore useful biomarkers for predicting the prognosis of acute stroke patients.

Method: In a single-center study, 216 (80% for the training set and 20% for the test set) acute stroke patients admitted to the Shenzhen Second People's Hospital between December 2019 to June 2021 were retrospectively recruited.

Organocatalytic Enantioselective Construction of Spiroketal Lactones Bearing Axial and Central Chirality via an Asymmetric Domino Reaction.

The catalytic asymmetric synthesis of chiral compounds with multiple stereogenic elements via a single catalytic process is challenging. This paper proposes a domino asymmetric electrophilic halocyclization strategy for constructing heterocycloalkenyl atropisomeric spiroketal lactones. A single catalyst was utilized to realize two independent stereodetermining steps.

Organocatalytic enantioselective construction of axially chiral (1)-isochromen-1-imines.

Heterocycloalkenyl atropisomers, derived from biaryl atropisomers and axially chiral styrenes, have emerged as a new class of nonbiaryl C-C atropisomers due to the benefit in improving the pharmacological activity and structural diversity. This paper proposes an intramolecular annulation strategy for constructing the heterocycloalkenyl atropisomers (1)-isochromen-1-imines by organocatalysis. Various heterocycloalkenyl atropisomers (1)-isochromen-1-imines were prepared in good to excellent yields with excellent enantioselectivity (up to 98% ee), and could be easily converted to atropisomeric lactones isocoumarins.

Golgi phosphoprotein 3 induces autophagy and epithelial-mesenchymal transition to promote metastasis in colon cancer.

In this study, we aimed to investigate whether and how Golgi phosphoprotein 3 (GOLPH3) facilitates colon cancer metastasis via the regulation of autophagy and epithelial-mesenchymal transition (EMT). The role GOLPH3 plays in colon cancer metastasis was analyzed using western blotting, immunohistochemistry, transwell, wound-healing, and zebrafish assays. Autophagy and EMT were assessed via RNA-sequencing (RNA-seq) analysis, mRFP-GFP-LC3 reporter assays, and their related markers.

Transmembrane protein 97 exhibits oncogenic properties via enhancing LRP6-mediated Wnt signaling in breast cancer.

Upregulation of transmembrane protein 97 (TMEM97) has been associated with progression and poor outcome in multiple human cancers, including breast cancer. Recent studies suggest that TMEM97 may be involved in the activation of the Wnt/β-catenin pathway. However, the molecular mechanism of TMEM97 action on Wnt/β-catenin signaling is completely unclear.

Associations of tea consumption with blood pressure progression and hypertension incidence.

Background: Association between tea consumption and incident hypertension remains uncertain. This study conducted to examine the health effects of tea consumption on blood pressure progression and hypertension incidence.

Methods: A population-based cohort of 38,913 Chinese participants without hypertension at baseline were included in the current study.

Risk factors for excess deaths during lockdown among older users of secondary care mental health services without confirmed COVID-19: A retrospective cohort study.

Objective: To investigate factors contributing to excess deaths of older patients during the initial 2020 lockdown beyond those attributable to confirmed COVID-19.

Methods: Retrospective cohort study comparing patients treated between 23 March 2020 and 14 June 2020, deemed exposed to the pandemic/lockdown, to patients treated between 18 December 2019 and 10 March 2020, deemed to be unexposed. Data came from electronic clinical records from secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), UK (catchment area population ∼0.

Cardiodynamic variables measured by impedance cardiography during a 6-minute walk test are reliable predictors of peak oxygen consumption in young healthy adults.

Accurate prediction of aerobic capacity is necessary to guide appropriate exercise prescription. It is common to use 6-minute walk distance (6MWD) to predict peak oxygen uptake (VO2peak) in the clinical environment. The aim of this study was to determine whether prediction of VO2peak can be improved by the inclusion of cardiovascular indices derived by impedance cardiography (ICG) during the 6MWT.

Fruit and vegetable consumption, cardiovascular disease, and all-cause mortality in China.

Evidence about the response patterns of fruit and vegetable consumption with the risk of cardiovascular disease (CVD) and all-cause mortality was inconsistent. These associations were examined using a large-scale, population-based Chinese cohort comprising 100,728 participants. A food-frequency questionnaire was used to assess fruit and vegetable consumption.