Active prophages in coral-associated Halomonas capable of lateral transduction.

Temperate phages can interact with bacterial hosts through lytic and lysogenic cycles via different mechanisms. Lysogeny has been identified as the major form of bacteria-phage interaction in the coral-associated microbiome. However, the lysogenic-to-lytic switch of temperate phages in ecologically important coral-associated bacteria and its ecological impact have not been extensively investigated. By studying the prophages in coral-associated Halomonas meridiana, we found that two prophages, Phm1 and Phm3, are inducible by the DNA-damaging agent mitomycin C and that Phm3 is spontaneously activated under normal cultivation conditions. Furthermore, Phm3 undergoes an atypical lytic pathway that can amplify and package adjacent host DNA, potentially resulting in lateral transduction. The induction of Phm3 triggered a process of cell-lysis accompanied by the formation of outer membrane vesicles (OMVs), and Phm3 attached to OMVs. This unique cell-lysis process was controlled by a four-gene lytic module within Phm3. Further analysis of the Tara Ocean dataset revealed that Phm3 represents a new group of temperate phages that are widely distributed and transcriptionally active in the ocean. Therefore, the combination of lateral transduction mediated by temperate phages and OMV transmission offers a versatile strategy for host-phage co-evolution in marine ecosystems.

Effects of Low-Intensity Pulsed Ultrasound on the Regulation of Free Fatty Acid Release in 3T3-L1 Cells.

OBJECTIVES: To investigate the effects of low-intensity pulsed ultrasound (LIPUS) on the proliferation, differentiation, and tumor necrosis factor-α (TNF-α)-induced lipolysis of 3T3-L1 cells, and to explore the feasibility of regulating the release of free fatty acids (FFA) to prevent lipotoxicity. METHODS: Different intensities (30, 60, 90, and 120 mW/cm2) of LIPUS were applied to 3T3-L1 preadipocytes for different durations (5, 10, 15, 20, 25, and 30 minutes). Appropriate parameters for subsequent experiments were selected by assessing cell viability. The effect of LIPUS on the proliferation and differentiation of 3T3-L1 cells was evaluated by microscope observation, flow cytometry, and lipid content determination. After treated with LIPUS and TNF-α (50 ng/mL), the degree of lipolysis was assessed by measuring the extracellular FFA content. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of relevant genes. RESULTS: Different parameters of LIPUS significantly enhance the viability of 3T3-L1 cells (P < .05), with 20 minutes and 30 mW/cm2 as the most suitable settings. After LIPUS treatment, 3T3-L1 cell proliferation accelerated, apoptosis rate and G1 phase cell proportion decreased, the content of lipid droplets and TG was increased in differentiated cells, while FFA release decreased (P < .05). The expression of PCNA, PPARγ, C/EBPα, Perilipin A mRNA increased, and the expression of TNF-α, ATGL, HSL mRNA decreased (P < .05). CONCLUSIONS: LIPUS could promote the proliferation and differentiation of 3T3-L1 cells and inhibit TNF-α-induced lipolysis, indicating its potential as a therapy for mitigating lipotoxicity caused by decompensated adipocytes.

In silico prediction of ocular toxicity of compounds using explainable machine learning and deep learning approaches.

The accurate identification of chemicals with ocular toxicity is of paramount importance in health hazard assessment. In contemporary chemical toxicology, there is a growing emphasis on refining, reducing, and replacing animal testing in safety evaluations. Therefore, the development of robust computational tools is crucial for regulatory applications. The performance of predictive models is heavily reliant on the quality and quantity of data. In this investigation, we amalgamated the most extensive dataset (4901 compounds) sourced from governmental GHS-compliant databases and literature to develop binary classification models of chemical ocular toxicity. We employed 12 molecular representations in conjunction with six machine learning algorithms and two deep learning algorithms to create a series of binary classification models. The findings indicated that the deep learning method GCN outperformed the machine learning models in cross-validation, achieving an impressive AUC of 0.915. However, the top-performing machine learning model (RF-Descriptor) demonstrated excellent performance with an AUC of 0.869 on the test set and was therefore selected as the best model. To enhance model interpretability, we conducted the SHAP method and attention weights analysis. The two approaches offered visual depictions of the relevance of key descriptors and substructures in predicting ocular toxicity of chemicals. Thus, we successfully struck a delicate balance between data quality and model interpretability, rendering our model valuable for predicting and comprehending potential ocular-toxic compounds in the early stages of drug discovery.

Characteristics of non-carbapenemase producing carbapenem-resistant Klebsiella pneumoniae from a tertiary hospital in China.

INTRODUCTION: The spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a substantial severe global public health burden. Non-carbapenemase-producing CRKP (non-CP-CRKP) is increasingly recognized as the source of severe infections. METHODOLOGY: We analyzed the genotypic, and phenotypic profiles of non-CP-CRKP strains with the whole-genome sequences isolated between 2017 and 2019 and the clinical characterization of non-CP-CRKP infection. RESULTS: A total of 91 CRKP strains were collected, of which 5 (5.49%) strains were non-CP-CRKP. Four strains were from male patients; three strains were isolated from the bile of patients who underwent biliary interventional surgery and four had a history of antibiotic exposure. Three strains were sequence type (ST)11, one was ST1, and one was ST5523. The non-CP-CRKP strains were insusceptible to ertapenem. Three strains were susceptible to amikacin. All the strains were susceptible to imipenem, meropenem, tigecycline, ceftazidime/avibatam and polymyxin B. The ß-lactamases of non-CP-CRKP predominantly included blaCTX-M, blaSHV, and blaTEM subtypes. Two site mutations in ompK36 (p.A217S and p.N218H) and four in ompK37 (p.I70M, p.I128M, p.N230G, and m233_None234insQ) were detected accounting for carbapenem resistance. Plasmids IncFI and IncFII were found in most strains. Genes encoding aerobactin, yersiniabactin and allantoin utilization were not detected in several isolates, and all non-CP-CRKP strains did not carry rmpA gene. CONCLUSIONS: Non-CP-CRKP infected patients had a history of previous antibiotic exposure or invasive procedures. Non-CP-CRKP strains were insusceptible to ertapenem. The mechanism of resistance includes ß-lactamases production and the site mutations in ompK36 and ompK37. Several virulence genes were not detected in non-CP-CRKP.

Extent and Resistance Patterns of Gram-negative Bacteria Isolated From 13 Hospitals in Shaoxing, Zhejiang Province.

Gram-negative bacteria are increasingly recognized as the sauce of severe infections. In recent years, epidemiological data has indicated that the drug resistance rate of Gram-negative bacteria has significantly increased. We analyzed the epidemiological surveillance data of gram-negative bacteria in Shaoxing City in 2021 by retrospectively collecting drug susceptibility data of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Burkholderia cepacian from thirteen tertiary hospitals. A total of 24,142 strains were collected from thirteen hospitals. The isolation rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, P. mirabilis, E. cloacae, and B. cepacian were 29.25%, 18.83%, 11.03%, 8.43%, 3.80%, 3.12%, and 0.75%, respectively. Among them, 2.86% were carbapenem-resistant E. coli, 12.98% were CRKP, 31.27% were CRPA, and 34.77% were CRAB. Carbapenem-resistant Enterobacterales were more sensitive to ceftazidime-avibactam and polymyxin. The drug resistance rates of P. aeruginosa and A. baumannii to polymyxin were 0 and 1.3%, but the resistance rates to ceftazidime-avibactam were 10.5% and 26.0%, respectively. Based on results from epidemiological data, CRKP had a high isolation rate and non-fermenting bacteria had a high resistance rate to ceftazidime-avibactam. All hospitals should strengthen monitoring and enact continuous intervention to reduce the generation and spread of drug-resistant bacteria.

Dehydrocurvularin-loaded mPEG-PLGA nanoparticles for targeted breast cancer drug delivery: preparation, characterization, in vitro, and in vivo evaluation.

Dehydrocurvularin (DCV) is a promising lead compound for anti-cancer therapy. Unfortunately, the development of DCV-based drugs has been hampered by its poor solubility and bioavailability. Herein, we prepared a DCV-loaded mPEG-PLGA nanoparticles (DCV-NPs) with improved drug properties and therapeutic efficacy. The spherical and discrete particles of DCV-NPs had a uniform diameter of 101.8 ± 0.45 nm and negative zeta potential of -22.5 ± 1.12 mV (pH = 7.4), and its entrapment efficiency (EE) and drug loading (DL) were ∼53.28 ± 1.12 and 10.23 ± 0.30%, respectively. In vitro the release of DCV-NPs lasted for more than 120 h in a sustained-release pattern, its antiproliferation efficacy towards breast cancer cell lines (MCF-7, MDA-MB-231, and 4T1) was better than that of starting drug DCV, and it could be efficiently and rapidly internalised by breast cancer cells. In vivo DCV-NPs were gradually accumulated in tumour areas of mice and significantly suppressed tumour growth. In summary, loading water-insoluble DCV onto nanoparticles has the potential to be an effective agent for breast cancer therapy with injectable property and tumour targeting capacity.

Discovery of Artemisinins as Microsomal Prostaglandins Synthase-2 Inhibitors for the Treatment of Colorectal Cancer via Chemoproteomics.

Colorectal cancer remains the second leading cause of cancer-related mortalities worldwide. While artemisinin (ART), a key active compound from the traditional Chinese medicinal herb Artemisia annua, has been recognized for its antiproliferative activity against colon cancer cells, its underlying molecular underpinnings remain elusive. Whereas promiscuity of heme-dependent alkylating of macromolecules, mainly proteins, has been seen pivotal as a universal and primary mode of action of ART in cancer cells, accumulating evidence suggests the existence of unique targets and mechanisms of actions contingent on cell or tissue specificities. Here, we employed photoaffinity probes to identify the specific targets responsible for ART's anti-colon cancer actions. Upon validation, microsomal prostaglandins synthase-2 emerged as a specific and reversible target of ART in HCT116 colorectal cancer cells, whose inhibition resulted in reduced cellular prostaglandin E2 biosynthesis and cell growth. Our discovery opens new opportunities for pharmacological treatment of colon cancer.

Recent advance of ATP citrate lyase inhibitors for the treatment of cancer and related diseases.

ATP citrate lyase (ACLY), a strategic metabolic enzyme that catalyzes the glycolytic to lipidic metabolism, has gained increasing attention as an attractive therapeutic target for hyperlipidemia, cancers and other human diseases. Despite of continual research efforts, targeting ACLY has been very challenging. In this field, most reported ACLY inhibitors are "substrate-like" analogues, which occupied with the same active pockets. Besides, some ACLY inhibitors have been disclosed through biochemical screening or high throughput virtual screening. In this review, we briefly summarized the cancer-related functions and the recent advance of ACLY inhibitors with a particular focus on the SAR studies and their modes of action. We hope to provide a timely and updated overview of ACLY and the discovery of new ACLY inhibitors.

Identification of risk factors for disseminated cryptococcosis in non-hiv patients: a retrospective analysis.

OBJECTIVE: This study aimed to investigate the potential risk factors associated with disseminated cryptococcosis in HIV-negative individuals. METHODS: A total of 106 HIV-negative patients with cryptococcal disease were enrolled. The observation group consisted of patients with disseminated cryptococcosis (DC), whereas the control groups included patients with pulmonary cryptococcosis (PC) and cryptococcal meningitis (CM). Univariate and multivariate logistic regression algorithms were used to explore the significant clinical and laboratory characteristics that affect the progression of cryptococcal infections. Finally, receiver operating characteristics (ROC) curves are applied to assess the diagnostic value of identified risk factors.LE: Kindly check the edit made in the title.I agree RESULTS: Of the 106 patients, 57 were diagnosed with pulmonary cryptococcosis, 22 with cryptococcal meningitis, and 27 with disseminated cryptococcosis. The logistic regression equation included five variables: diabetes, decompensated liver cirrhosis, long-term use of immunosuppressive agents, decreased serum albumin level, and elevated plasma cytokine IL-10 level. The ROC curves showed that albumin (AUC > 0.7), IL-10 (AUC > 0.7) and decompensated liver cirrhosis (AUC > 0.6) have relatively high diagnostic capacity in predicting the progression of Cryptococcus. CONCLUSION: This study identified elevated IL-10 levels as an independent risk factor for developing disseminated cryptococcosis in the control groups. Furthermore, decompensated liver cirrhosis and decreased serum albumin independently affected the progression of cryptococcosis in the CM and PC groups, respectively.

Endophytic Bacterium Flexivirga meconopsidis sp. nov. with Plant Growth-Promoting Function, Isolated from the Seeds of Meconopsis integrifolia.

Strain Q11T of an irregular coccoid Gram-positive bacterium, aerobic and non-motile, was isolated from Meconopsis integrifolia seeds. Strain Q11T grew optimally in 1% (w/v) NaCl, pH 7, at 30 °C. Strain Q11T is most closely related to Flexivirga, as evidenced by 16S rRNA gene analysis, and shares the highest similarity with Flexivirga aerilata ID2601ST (99.24%). Based on genome sequence analysis, the average nucleotide identity and digital DNA-DNA hybridization values of strains Q11T and D2601ST were 88.82% and 36.20%, respectively. Additionally, strain Q11T showed the abilities of nitrogen fixation and indole acetic acid production and was shown to promote maize growth under laboratory conditions. Its genome contains antibiotic resistance genes (the vanY gene in the vanB cluster and the vanW gene in the vanI cluster) and extreme environment tolerance genes (ectoine biosynthetic gene cluster). Shotgun proteomics also detected antibiotic resistance proteins (class A beta-lactamases, D-alanine ligase family proteins) and proteins that improve plant cold tolerance (multispecies cold shock proteins). Strain Q11T was determined to be a novel species of the genus Flexivirga, for which the name Flexivirga meconopsidis sp. nov. is proposed. The strain type is Q11T (GDMCC 1.3002T = JCM 36020 T).

Structure-Based Ligand Discovery Targeting the Transmembrane Domain of Frizzled Receptor FZD7.

Despite the essential roles of Frizzled receptors (FZDs) in mediating Wnt signaling in embryonic development and tissue homeostasis, ligands targeting FZDs are rare. A few antibodies and peptide modulators have been developed that mainly bind to the family-conserved extracellular cysteine-rich domain of FZDs, while the canonical binding sites in the transmembrane domain (TMD) are far from sufficiently addressed. Based on the recent structures of FZDs, we explored small-molecule ligand discovery by targeting TMD. From the ChemDiv library with ∼1.6 million compounds, we identified compound F7H as an antagonist of FZD7 with an IC50 at 1.25 ± 0.38 µM. Focusing on this hit, the structural dissection study, together with computing studies such as molecular docking, molecular dynamics simulation, and free energy perturbation calculations, defined the binding pocket with key residue recognition. Our results revealed the structural basis of ligand recognition and demonstrated the feasibility of structure-guided ligand discovery for FZD7-TMD.

Molecular Epidemiology and Virulence Gene Analysis of Methicillin-Resistant Staphylococcus aureus Associated with Skin and Soft Tissue Infections in the Shaoxing Region.

Objective: This study aimed to investigate the prevalence, molecular types, and virulence genes of methicillin-resistant Staphylococcus aureus (MRSA) causing skin and soft tissue infections (SSTIs) in the Shaoxing region. Methods: MRSA strains were collected from patients with SSTIs in Shaoxing People's Hospital from January 2019 to December 2019. We conducted SCCmec typing, Staphylococcus protein A (SPA) typing, multilocus sequence typing (MLST), and virulence gene analysis using whole-genome sequencing on all MRSA strains. Results: The detection rate of community-acquired MRSA (CA-MRSA) isolated from SSTI patients in our hospital was 33.3% (6/18). The primary SCCmec types of CA-MRSA strains were IV and V, with IVg(2B) and V(5C2&5) accounting for 16.7% each. Hospital-acquired MRSA (HA-MRSA) strains primarily exhibited SCCmec types IVa(2B) (25.0%), followed by II(2A) (16.7%), V(5C2) (16.7%), and V(5C2&5) (8.3%). SPA typing indicated that CA-MRSA strains causing SSTIs were predominantly t437 (14.3%), t034 (14.3%), t309 (14.3%), t4549 (14.3%), and t7637 (14.3%). The primary SPA type of HA-MRSA strains was t311 (16.7%). MLST typing revealed that the main sequence types (STs) of CA-MRSA strains causing SSTIs were ST22 (33.3%), followed by ST398, ST59, ST88, and ST630, each accounting for 16.7%. The principal STs of HA-MRSA strains were ST398 (16.7%), ST59 (16.7%), ST88 (16.7%), and ST5 (16.7%), followed by ST22, ST630, ST6, and ST188, each at 8.3%. The primary clones of CA-MRSA strains causing SSTIs were ST59-t437-IVg(2B) (16.7%) and ST630-t4549-V(5C2&5) (16.7%), while the primary clones of HA-MRSA strains were ST59-t437-IVa(2B), ST630-t4549-V(5C2&5), ST6-t304-IVa(2B), ST5-t311-II(2A), ST59-t172-IVa(2B), ST398-t571-V(5C2), ST398-t034-V(5C2), and ST5-t311-II(2A), each accounting for 8.3%. The detection rate of the lukSF-PV virulence gene was higher in CA-MRSA strains (50.0%) than in HA-MRSA strains (16.7%). Conclusions: The isolation rate of CA-MRSA strains causing SSTIs was high in Shaoxing People's Hospital, with ST59-t437-IVg(2B) and ST630-t4549-V(5C2&5) being the predominant clones. MRSA strains exhibited multiple virulence genes, with the lukSF-PV gene having a higher detection rate in CA-MRSA strains, signifying its importance as a virulence factor in CA-MRSA.

Atractylodes macrocephala Koidz polysaccharide improves glycolipid metabolism disorders through activation of aryl hydrocarbon receptor by gut flora-produced tryptophan metabolites.

Polysaccharides are known to confer protection against glycolipid metabolism disorders (GMD) by regulating intestinal flora. In this study, a heterogeneous acidic heteropolysaccharide with high molecular weight mainly composed of fructose was isolated from Atractylodes macrocephala Koidz (AMP). Supplementation with AMP was shown to improve diet-induced GMD in a rat model, including decreasing the levels of serum triglycerides, total cholesterol, and glucose, and improving hepatic lipidosis and islet cells morphologies. AMP-treated rats also exhibited modified intestinal flora with enrichments of intestinal Lactobacillus and Rothia species, which was accompanied by increased tryptophan metabolites such as indole-3-propionic acid, indole, tryptamine, and tryptophol. These metabolites promote the expression of intestinal aryl hydrocarbon receptor (AhR) in nuclear fractions. AhR activation increased the expression levels of IL-22 and GLP-1 proteins and mRNA. IL-22 reduced systemic LPS by upregulating the expression of tight junction proteins, antimicrobial peptides, and mucin to ameliorate intestinal barrier function, and activated the hepatic IL-22R/Stat3/Acox1 signaling pathway to improve lipid metabolism. GLP-1 activated the pancreatic GLP-1R/p-CREB signaling pathway to ameliorate ß-cell injury and improve insulin resistance. Therefore, the intestinal microbial-tryptophan metabolism-AhR pathway was deduced to be a mechanism by which this polysaccharide improves GMD.

TGF-ß1/SMAD3 Regulates Programmed Cell Death 5 That Suppresses Cardiac Fibrosis Post-Myocardial Infarction by Inhibiting HDAC3.

BACKGROUND: Progressive cardiac fibrosis leads to ventricular wall stiffness, cardiac dysfunction, and eventually heart failure, but the underlying mechanism remains unexplored. PDCD5 (programmed cell death 5) ubiquitously expresses in tissues, including the heart; however, the role of PDCD5 in cardiac fibrosis is largely unknown. Therefore, this study aims at exploring the possible role and underlying mechanisms of PDCD5 in the pathogenesis of cardiac fibrosis. METHODS AND RESULTS: PDCD5 levels were found to be elevated in the serum obtained from patients with cardiac fibrosis, in fibrotic mice heart tissues after myocardial infarction, and in cardiac fibroblasts stimulated by Ang II (angiotensin II)- or TGF-ß1 (transforming growth factor-ß1). Overexpression of PDCD5 in cardiac fibroblasts or treatment with PDCD5 protein reduced the expression of profibrogenic proteins in response to TGF-ß1 stimulation, while knockdown of PDCD5 increased fibrotic responses. It has been demonstrated that SMAD3, a protein that is also known as mothers against decapentaplegic homolog 3, directly upregulated PDCD5 during cardiac fibrosis. Subsequently, the increased PDCD5 promoted HDAC3 (histone deacetylase 3) ubiquitination, thus, inhibiting HDAC3 to reduce fibrotic responses. Fibroblast-specific knock-in of PDCD5 in mice ameliorated cardiac fibrosis after myocardial infarction and enhanced cardiac function, and these protective effects were eliminated by AAV9-mediated HDAC3 overexpression. CONCLUSIONS: The findings of this study demonstrated that PDCD5 is upregulated by SMAD3 during cardiac fibrosis, which subsequently ameliorated progressive fibrosis and cardiac dysfunction through HDAC3 inhibition. Thus, this study suggests that PDCD5 functions as a negative feedback factor on fibrotic signaling pathways and might serve as a potential therapeutic target to suppress the progression of fibrotic responses.

BBOF1 is required for sperm motility and male fertility by stabilizing the flagellar axoneme in mice.

The sperm flagellum is a specialized type of motile cilium composed of a typical "9 + 2" axonemal structure with peri-axonemal structures, such as outer dense fibers (ODFs). This flagellar arrangement is crucial for sperm movement and fertilization. However, the association of axonemal integrity with ODFs remains poorly understood. Here, we demonstrate that mouse BBOF1 could interact with both MNS1, an axonemal component, and ODF2, an ODF protein, and is required for sperm flagellar axoneme maintenance and male fertility. BBOF1 is expressed exclusively in male germ cells from the pachytene stage onwards and is detected in sperm axoneme fraction. Spermatozoa derived from Bbof1-knockout mice exhibit a normal morphology, however, reduced motility due to the absence of certain microtubule doublets, resulting in the failure to fertilize mature oocytes. Furthermore, BBOF1 is found to interact with ODF2 and MNS1 and is also required for their stability. Our findings in mice suggest that Bbof1 could also be essential for human sperm motility and male fertility, thus is a novel potential candidate gene for asthenozoospermia diagnosis.

CMTM3 deficiency induces cardiac hypertrophy by regulating MAPK/ERK signaling.

OBJECTIVES: Cardiac hypertrophy is the heart's compensatory response stimulated by various pathophysiological factors. However, prolonged cardiac hypertrophy poses a significant risk of progression to heart failure, lethal arrhythmias, and even sudden cardiac death. For this reason, it is crucial to effectively prevent the occurrence and development of cardiac hypertrophy. CMTM is a superfamily of human chemotaxis, which is involved in immune response and tumorigenesis. CMTM3 expressed widely in tissues, including the heart, but its cardiac function remains unclear. This research aims to explore the effect and mechanism of CMTM3 in the development of cardiac hypertrophy. METHODS AND RESULTS: We generated a Cmtm3 knockout mouse model (Cmtm3-/-) as the loss-of-function approach. CMTM3 deficiency induced cardiac hypertrophy and further exacerbated hypertrophy and cardiac dysfunction stimulated by Angiotensin Ⅱ infusion. In Ang Ⅱ-infusion stimulated hypertrophic hearts and phenylephrine-induced hypertrophic neonatal cardiomyocytes, CMTM3 expression significantly increased. However, adenovirus-mediated overexpression of CMTM3 inhibited the hypertrophy of rat neonatal cardiomyocytes induced by PE stimulation. In terms of mechanism, RNA-seq data revealed that Cmtm3 knockout-induced cardiac hypertrophy was related to MAPK/ERK activation. In vitro, CMTM3 overexpression significantly inhibited the increased phosphorylation of p38 and ERK induced by PE stimulation. CONCLUSIONS: CMTM3 deficiency induces cardiac hypertrophy and aggravates hypertrophy and impaired cardiac function stimulated by angiotensin Ⅱ infusion. The expression of CMTM3 increases during cardiac hypertrophy, and the increased CMTM3 can inhibit further hypertrophy of cardiomyocytes by inhibiting MAPK signaling. Thus, CMTM3 plays a negative regulatory effect in the occurrence and development of cardiac hypertrophy.

PyQMC: An all-Python real-space quantum Monte Carlo module in PySCF.

We describe a new open-source Python-based package for high accuracy correlated electron calculations using quantum Monte Carlo (QMC) in real space: PyQMC. PyQMC implements modern versions of QMC algorithms in an accessible format, enabling algorithmic development and easy implementation of complex workflows. Tight integration with the PySCF environment allows for a simple comparison between QMC calculations and other many-body wave function techniques, as well as access to high accuracy trial wave functions.

Broadband UV-Excitation and Red/Far-Red Emission Materials for Plant Growth: Tunable Spectrum Conversion in Eu3+,Mn4+ Co-doped LaAl0.7Ga0.3O3 Phosphors.

Broadband ultraviolet (UV) excitation and red/far-red emission phosphors can effectively convert solar spectrum to enhance photosynthesis and promote morphogenesis in plants. Based on the above application requirements, Eu3+ single-doped LaAl1-yGayO3 solid solutions and Eu3+,Mn4+ codoped LaAl0.7Ga0.3O3 phosphors were designed and synthesized in this work. The LaAl0.7Ga0.3O3:0.05Eu3+ (LAG:Eu3+) phosphor exhibits a strong charge transfer band (CTB) excitation and characteristic 5D0 → 7F2 transition red emission (619 nm), which is very similar to the luminescence properties of Eu3+-organic ligand compound (EuL3). Rietveld refinement studies further revealed that the cation substitution disturbs the site symmetry. The optimal Eu3+, Mn4+ co-doped LaAl0.7Ga0.3O3 (LAG:Eu,Mn) phosphor possesses a dual-band excitation spectrum in broadband ultraviolet (UVA, UVB) area and a dual-band emission spectrum within red/far-red area. Under the sunlight radiation, the real-time spectrum of luminous laminated glasses fabricated by coating the LAG:Eu,Mn phosphor shows the percentage of radiant intensity in the red/far-red region significantly increases, suggesting that the phosphor can be a promising candidate for solar spectral conversion in plant cultivation. We believe this work provides a new idea for developing novel broadband ultraviolet excitation and red/far-red emission phosphors.

The beneficial effects of Polygonatum sibiricum Red. superfine powder on metabolic hypertensive rats via gut-derived LPS/TLR4 pathway inhibition.

BACKGROUND: Metabolic hypertension (MH) is characterized by elevated blood pressure accompanied by metabolic abnormalities, with the gut-derived lipopolysaccharide/toll like receptor 4 (LPS/TLR4) pathway an important triggering mechanism. The conventional Chinese plant Polygonatum sibiricum Red. is traditionally used as a medicinal and edible food source. Currently, several studies have examined its anti-obesity and anti-diabetic actions, with potential roles for MH treatment; however, specific P. sibiricum Red. roles in MH and associated mechanisms remain unclear. OBJECTIVES: Our purpose was to identify the effects and mechanisms of P. sibiricum Red. superfine powder (PSP) in a MH rat model triggered by high sugar and high fat compounds in an excessive alcohol diet (ACHSFDs). METHODS: A MH rat model was induced by ACHSFDs, and PSP was administered daily at 0.5 and 1.0 g/kg doses, respectively. Firstly, the effects of PSP on MH were assessed using blood pressure, serum lipid, and lipid deposition assays in the liver. Changes in intestinal flora were detected by high-throughput 16S rRNA sequencing, while metabolite short-chain fatty acids (SCFAs) and LPS levels were quantified by gas chromatography (GC) and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin & eosin (H&E) staining and transmission electron microscopy (TEM) were performed to evaluate histopathological changes in the rat colon. d-lactic acid (d-LA) levels and tight junction proteins (TJPs) expression were also measured to assess intestinal barrier function. Also, aortic endothelial microstructures, serum endothelin 1 (ET-1), and nitric oxide (NO) levels were investigated to determine vascular endothelial function. Finally, the TLR4/MyD88 signaling pathway in the aorta and gut was evaluated by western blotting, immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Blood pressure and blood lipid metabolism disorders induced by ACHSFDs in MH rats were improved by PSP administration. Intestinal flora analyses revealed decreased SCFAs and LPS levels following PSP administration, which was accompanied by increased Streptococcus species levels and decreased Desulfobacter and Desulfovibrio species levels. PSP increased SCFAs levels, and the expression of SCFAs receptors GPCR41 and GPCR43 in the colon. Meanwhile, the expression of tight junction proteins (TJPs) such as Claudin-1, occludin were upregulated in the ileum and colon, while TLR4 and MyD88 were downregulated, thereby strengthening intestinal barrier integrity and reducing serum LPS levels. Additionally, PSP treatment improved vascular endothelial function by inhibiting the TLR4/MyD88 pathway in vessels, improving vascular endothelial cell shedding, and regulating the NO and ET-1 balance. CONCLUSIONS: We demonstrated the beneficial effects and potential mechanisms of PSP in our MH rat model. Based on gut microbiota structure modulation and intestinal barrier improvements, PSP inhibited LPS-induced vascular TLR4/MyD88 signaling activation to improve vascular endothelial function, which in turn reduced blood pressure. Our study provides valuable insights on PSP therapy for MH.

Leucobacter chinensis sp. nov., with plant growth-promoting potential isolated from field soil after seven-years continuous maize cropping.

A novel Gram-stain-positive, aerobic, non-motile and rod-shaped bacterium, designated strain NC76-1T, was isolated from soil from a field that had undergone seven years continuous maize cropping from Liuba town located in Zhangye city, Gansu province, PR China. Colonies of strain NC76-1T were white, opaque and circular with a convex shape. The isolate was found to be able to grow at 10-40 °C (optimum 30 °C), pH 6.0 to 12.0 (optimum 7.0-8.0) and with 0-5.0 % (w/v) NaCl (optimum 0%). On the basis of the results of 16S rRNA gene sequence analysis, the strain fell within the clade of the genus Leucobacter, showing the highest sequence similarities with Leucobacter iarius 40T (97.4%), Leucobacter aridicollis CIP 108388T (97.0%), Leucobacter chromiireducens subsp. solipictus TAN 31504T (96.7%) and Leucobacter denitrificans M1T8B10T (96.7%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between NC76-1T and its closest relatives, L. iarius 40T, L. aridicollis CIP 108388T, L. chromiireducens subsp. solipictus TAN 31504T and L. denitrificans M1T8B10T were ≤73.5 % and 20.3%, respectively. The genomic DNA G+C content of NC76-1T was 61.5 mol%. It presented MK-11 as the predominant menaquinone. The major cellular fatty acids were anteiso-C15 : 0 (49.2 %) and iso-C16 : 0 (35.7%). The major polar lipids were found to be diphosphatidyglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminoglycolipid, five glycolipid and one unidentified lipids. The cell wall amino acids were 2,4-diaminobutyric acid, alanine, glutamic acid, glycine and threonine. On the basis of the phylogenetic, phenotypic and chemotaxonomic characteristics, strain NC76-1T is concluded to represent a novel species within the genus Leucobacter, for which the name Leucobacter chinensis sp. nov. is proposed. The type strain is NC76-1T (GDMCC 1.2286T= JCM 34651T).