A nomogram-based predictive model for tooth survival in Chinese patients with periodontitis: An 11-year retrospective cohort study.

AIM: To develop a nomogram-based predictive model of tooth survival by comprehensively analysing clinical and radiographic risk factors of tooth loss (TL). MATERIALS AND METHODS: In this study, 3447 teeth of 131 subjects who underwent non-surgical periodontal treatment were examined retrospectively within a mean follow-up period of 11.6 years. The association of risk factors including clinical and radiographic parameters with TL was assessed using univariate and multivariate Cox regression analyses. A nomogram-based predictive model was developed, and its validation and discriminatory ability were analysed. RESULTS: In all, 313 teeth were lost in 94 patients in this study (overall tooth loss [OTL] 9.08%; 0.21 teeth/patient/year). Male, heavy smoking, molar teeth, probing depth (PD), attachment loss (AL), tooth mobility and radiographic bone loss were significantly associated with TL (p < .05). A gradient effect of tooth mobility on TL increased from degree I to III versus none (p < .0001). The area under the curve (AUC) of the model was 0.865. Calibration curve and decision curve analysis demonstrated good performance and high net benefit, respectively. CONCLUSIONS: Adopting a specific nomogram could facilitate the prediction of tooth survival and the development of tailored treatment plans in Chinese patients with advanced periodontitis.

Exploring the origins and evolution of oxygenic and anoxygenic photosynthesis in deeply branched Cyanobacteriota.

Cyanobacteriota, the sole prokaryotes capable of oxygenic photosynthesis (OxyP), occupy a unique and pivotal role in Earth's history. While the notion that OxyP may have originated from Cyanobacteriota is widely accepted, its early evolution remains elusive. Here, by using both metagenomics and metatranscriptomics, we explore 36 metagenome-assembled genomes (MAGs) from hot spring ecosystems, belonging to two deep-branching cyanobacterial orders: Thermostichales and Gloeomargaritales. Functional investigation reveals that Thermostichales encode the crucial thylakoid membrane biogenesis protein, Vipp1. Based on the phylogenetic results, we infer that the evolution of the thylakoid membrane predates the divergence of Thermostichales from other cyanobacterial groups and that Thermostichales may be the most ancient lineage known to date to have inherited this feature from their common ancestor. Apart from OxyP, both lineages are potentially capable of sulfide-driven anoxygenic photosynthesis (AnoxyP) by linking sulfide oxidation to the photosynthetic electron transport chain. Unexpectedly, this AnoxyP capacity appears to be an acquired feature, as the key gene sqr was horizontally transferred from later-evolved cyanobacterial lineages. The presence of two D1 protein variants in Thermostichales suggests the functional flexibility of photosystems, ensuring their survival in fluctuating redox environments. Furthermore, all MAGs feature streamlined phycobilisomes with a preference for capturing longer-wavelength light, implying a unique evolutionary trajectory. Collectively, these results reveal the photosynthetic flexibility in these early-diverging cyanobacterial lineages, shedding new light on the early evolution of Cyanobacteriota and their photosynthetic processes.

Phylogenomic analyses and comparative genomic studies of Thermus strains isolated from Tengchong and Tibet Hot Springs, China.

Genus Thermus is the main focus of researcher among the thermophiles. Members of this genus are the inhabitants of both natural and artificial thermal environments. We performed phylogenomic analyses and comparative genomic studies to unravel the genomic diversity among the strains belonging to the genus Thermus in geographically different thermal springs. Sixteen Thermus strains were isolated and sequenced from hot springs, Qucai hot springs in Tibet and Tengchong hot springs in Yunnan, China. 16S rRNA gene based phylogeny and phylogenomic analyses based on concatenated set of 971 Orthologous Protein Families (supermatrix and gene content methods) revealed a mixed distribution of the Thermus strains. Whole genome based phylogenetic analysis showed, all 16 Thermus strains belong to five species; Thermus oshimai (YIM QC-2-109, YIM 1640, YIM 1627, 77359, 77923, 77838), Thermus antranikianii (YIM 73052, 77412, 77311, 71206), Thermus brokianus (YIM 73518, 71318, 72351), Thermus hydrothermalis (YIM 730264 and 77927) and one potential novel species 77420 forming clade with Thermus thalpophilus SYSU G00506T. Although the genomes of different strains of Thermus of same species were highly similar in their metabolic pathways, but subtle differences were found. CRISPR loci were detected through genome-wide screening, which showed that Thermus isolates from two different thermal locations had well developed defense system against viruses and adopt similar strategy for survival. Additionally, comparative genome analysis screened competence loci across all the Thermus genomes which could be helpful to acquire DNA from environment. In the present study it was found that Thermus isolates use two mechanism of incomplete denitrification pathway, some Thermus strains produces nitric oxide while others nitrious oxide (dinitrogen oxide), which show the heterotrophic lifestyle of Thermus genus. All isolated organisms encoded complete pathways for glycolysis, tricarboxylic acid and pentose phosphate. Calvin Benson Bassham cycle genes were identified in genomes of T. oshimai and T. antranikianii strains, while genomes of all T. brokianus strains and organism 77420 were lacking. Arsenic, cadmium and cobalt-zinc-cadmium resistant genes were detected in genomes of all sequenced Thermus strains. Strains 77,420, 77,311, 73,518, 77,412 and 72,351 genomes were found harboring genes for siderophores production. Sox gene clusters were identified in all sequenced genomes, except strain YIM 730264, suggesting a mode of chemolithotrophy. Through the comparative genomic analysis, we also identified 77420 as the genome type species and its validity as novel organism was confirmed by whole genome sequences comparison. Although isolate 77420 had 99.0% 16S rRNA gene sequence similarity with T. thalpophilus SYSU G00506T but based on ANI 95.86% (Jspecies) and digital DDH 68.80% (GGDC) values differentiate it as a potential novel species. Similarly, in the phylogenomic tree, the novel isolate 77,420 forming a separate branch with their closest reference type strain T. thalpophilus SYSU G00506T.

Cofitness network connectivity determines a fuzzy essential zone in open bacterial pangenome.

Most in silico evolutionary studies commonly assumed that core genes are essential for cellular function, while accessory genes are dispensable, particularly in nutrient-rich environments. However, this assumption is seldom tested genetically within the pangenome context. In this study, we conducted a robust pangenomic Tn-seq analysis of fitness genes in a nutrient-rich medium for Sinorhizobium strains with a canonical open pangenome. To evaluate the robustness of fitness category assignment, Tn-seq data for three independent mutant libraries per strain were analyzed by three methods, which indicates that the Hidden Markov Model (HMM)-based method is most robust to variations between mutant libraries and not sensitive to data size, outperforming the Bayesian and Monte Carlo simulation-based methods. Consequently, the HMM method was used to classify the fitness category. Fitness genes, categorized as essential (ES), advantage (GA), and disadvantage (GD) genes for growth, are enriched in core genes, while nonessential genes (NE) are over-represented in accessory genes. Accessory ES/GA genes showed a lower fitness effect than core ES/GA genes. Connectivity degrees in the cofitness network decrease in the order of ES, GD, and GA/NE. In addition to accessory genes, 1599 out of 3284 core genes display differential essentiality across test strains. Within the pangenome core, both shared quasi-essential (ES and GA) and strain-dependent fitness genes are enriched in similar functional categories. Our analysis demonstrates a considerable fuzzy essential zone determined by cofitness connectivity degrees in Sinorhizobium pangenome and highlights the power of the cofitness network in understanding the genetic basis of ever-increasing prokaryotic pangenome data.

Cultivation of novel Atribacterota from oil well provides new insight into their diversity, ecology, and evolution in anoxic, carbon-rich environments.

BACKGROUND: The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood. RESULTS: We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34TS, both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11T and Phoenicimicrobium oleiphilum HX-OS.bin.34TS ferment sugars and n-alkanes, respectively, producing H2, CO2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments. CONCLUSION: Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract.

Multi-omics insights into the function and evolution of sodium benzoate biodegradation pathway in Benzoatithermus flavus gen. nov., sp. nov. from hot spring.

Biodegradation stands as an eco-friendly and effective approach for organic contaminant remediation. However, research on microorganisms degrading sodium benzoate contaminants in extreme environments remains limited. In this study, we report to display the isolation of a novel hot spring enriched cultures with sodium benzoate (400 mg/L) as the sole carbon source. The results revealed that the phylum Pseudomonadota was the potential sodium benzoate degrader and a novel genus within the family Geminicoccaceae of this phylum. The isolated strain was named Benzoatithermus flavus SYSU G07066T and was isolated from HNT-2 hot spring samples. Genomic analysis revealed that SYSU G07066T carried benABC genes and physiological experiments indicated the ability to utilize sodium benzoate as a sole carbon source for growth, which was further confirmed by transcriptomic data with expression of benABC. Phylogenetic analysis suggested that Horizontal Gene Transfer (HGT) plays a significant role in acquiring sodium benzoate degradation capability among prokaryotes, and SYSU G07066T might have acquired benABC genes through HGT from the family Acetobacteraceae. The discovery of the first microorganism with sodium benzoate degradation function from a hot spring enhances our understanding of the diverse functions within the family Geminicoccaceae. This study unearths the first novel genus capable of efficiently degrading sodium benzoate and its evolution history at high temperatures, holding promising industrial applications, and provides a new perspective for further exploring the application potential of hot spring "microbial dark matter".

Determination of key volatile fishy substances of sea cucumber powder during the processing and their removal by supercritical fluid extraction.

More than 40 volatile compounds were detected in sea cucumber powder during the processing (through freeze-dried, desalination, supercritical fluid extraction and ultra-micro grinding) by multiple methods including e-nose, GC-IMS and GC-MS. It has been determined that aldehydes are the predominant volatile substances in the original freeze-dried sample, accounting for about 30 % of the total volatile substances. In addition, we established a supercritical fluid extraction strategy that could efficiently remove the aldehydes from the sea cucumber powder. GC-IMS and GC-MS showed that the relative content of aldehydes significantly decreased by 14 % and 28 %, respectively. Quantification of aldehydes using GC-MS showed a significant decrease in octanal from 927 µg/kg to 159 µg/kg. Further investigation combined with OAV analysis showed that 17 volatile substances in the freeze-dried sea cucumber powder were considered to be the predominant volatile compounds (OAV > 1).The primary fishy compounds found in sea cucumber powder were identified as hexanal, octanal, and an unidentified compound using GC-O, which can be effectively removed (OAV can't been estimated) by the supercritical fluid extraction strategy we established.

Risks for prolonged mechanical ventilation and reintubation after cervical malignant tumor surgery: a nested case-control study.

PURPOSE: Prolonged mechanical ventilation (PMV) and reintubation are among the most serious postoperative adverse events associated with malignant cervical tumors. In this study, we aimed to clarify the incidence, characteristics, and risk factors for PMV and reintubation in target patients. METHODS: This retrospective nested case-control study was performed between January 2014 and January 2020 at a large spinal tumor center in China. Univariate analysis was used to identify the possible risk factors associated with PMV and reintubation. Logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) with covariates of a probability < 0.05 in univariate analysis. RESULTS: From a cohort of 560 patients with primary malignant (n = 352) and metastatic (n = 208) cervical tumors, 27 patients required PMV and 20 patients underwent reintubation. The incidence rates of PMV and reintubation were 4.82% and 3.57%, respectively. Three variables (all p < 0.05) were independently associated with an increased risk of PMV: Karnofsky Performance Status < 50 compared to ≥ 80, operation duration ≥ 8 h compared to < 6 h, and C4 nerve root encased by the tumor. Longer operative duration and preoperative hypercapnia (all p < 0.05) were independent risk factors for postoperative reintubation, both of which led to longer length of stay (32.6 ± 30.8 vs. 10.7 ± 5.95 days, p < 0.001), with an in-hospital mortality of 17.0%. CONCLUSION: Our results demonstrate the risk factors for PMV or reintubation after surgery for malignant cervical tumors. Adequate assessment, early detection, and prevention are necessary for this high-risk population.

The effect of external fixator on bone metabolism in patients with open fracture of extremities.

This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), ß-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased ß-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.

The role of histone deacetylases in inflammatory respiratory diseases: an update.

INTRODUCTION: Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues of histones and other proteins, generally leading to a closed chromosomal configuration and transcriptional repression. Different HDACs have distinct substrate specificities and functions in different biological processes. Accumulating evidence indicates that HDACs play a key role in the pathogenesis of multiple respiratory diseases. AREAS COVERED: After an extensive search of the PubMed database, Web of Science and ClinicalTrials.gov, covering the period from 1992 to 2024, this review summarizes recent advances in understanding the role of HDACs in inflammatory respiratory diseases, including allergic rhinitis (AR), chronic rhinosinusitis (CRS), asthma and chronic obstructive pulmonary disease (COPD). We also examine recent progress on the efficacy and potential use of histone deacetylase inhibitors (HDACi) for the treatment of these diseases. EXPERT OPINION: Available data indicate that HDACs play an important role in the development of common inflammatory respiratory diseases, and HDACi have shown promise as treatments for these diseases. However, the exact roles and underlying mechanisms of specific HDACs in disease pathogenesis require further study. Additional work is necessary to develop novel potent HDACi with high isoform selectivity.

Translocator Protein 18 kDa Tracer 18F-FDPA PET/CTA Imaging for the Evaluation of Inflammation in Vulnerable Plaques.

Inflammation induced by activated macrophages within vulnerable atherosclerotic plaques (VAPs) constitutes a significant risk factor for plaque rupture. Translocator protein (TSPO) is highly expressed in activated macrophages. This study investigated the effectiveness of TSPO radiotracers, 18F-FDPA, in detecting VAPs and quantifying plaque inflammation in rabbits. 18 New Zealand rabbits were divided into 3 groups: sham group A, VAP model group B, and evolocumab treatment group C. 18F-FDPA PET/CTA imaging was performed at 12, 16, and 24 weeks in all groups. Optical coherence tomography (OCT) was performed on the abdominal aorta at 24 weeks. The VAP was defined through OCT images, and ex vivo aorta PET imaging was also performed at 24 weeks. The SUVmax and SUVmean of 18F-FDPA were measured on the target organ, and the target-to-background ratio (TBRmax) was calculated as SUVmax/SUVblood pool. The arterial sections of the isolated abdominal aorta were analyzed by HE staining, CD68 and TSPO immunofluorescence staining, and TSPO Western blot. The results showed that at 24 weeks, the plaque TBRmax of 18F-FDPA in group B was significantly higher than in groups A and C. Immunofluorescence staining of CD68 and TSPO, as well as Western blot, confirmed the increased expression of macrophages and TSPO in the corresponding regions of group B. HE staining revealed an increased presence of the lipid core, multiple foam cells, and inflammatory cell infiltration in the area with high 18F-FDPA uptake. This indicates a correlation between 18F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.

Ferviditalea candida gen. nov., sp. nov., a novel member of the family Paenibacillaceae isolated from a geothermal area.

OBJECTIVE: The family Paenibacillaceae is linked to the order Caryophanales. Paenibacillaceae members residing in compost or soil play crucial roles in nutrient recycling and breaking down complex organic materials. However, our understanding of Paenibacillaceae remains limited. METHODS: Strain SYSU GA230002T was conclusively identified using a polyphasic taxonomic approach frequently utilized in bacterial systematics. Standard microbiological techniques were employed to characterize the morphology and biochemistry of strain SYSU GA230002T. RESULTS: An anaerobic and gram--negative bacterium, designated SYSU GA230002T, was isolated from geothermally heated soil of Tengchong, Yunnan Province, south-west China. Phylogenetic analyses based on 16S rRNA gene sequences and genomes showed that strain SYSU GA230002T belongs to the family Paenibacillaceae. 16S rRNA gene sequence similarity (<94.0 %), ANI (<71.95 %) and AAI values (<58.67 %) between strain SYSU GA230002T with other members of the family were lower than the threshold values recommended for distinguishing novel species. Growth was observed at 30-45 °C (optimum, 37 °C), pH 7.0-8.0 (optimum, pH 7.5) and in 0-3.0 % (w/v) NaCl concentrations (optimum, 0 %). The major fatty acids detected were anteiso-C15:0, iso-C16:0 and iso-C17:0. The polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified phospholipid, one unidentified aminolipid and two unidentified glycolipids. The respiratory quinone was MK-7. The DNA G + C content of strain SYSU GA230002T was 49.87 %. CONCLUSION: Based on the results of morphological, physiological properties, and chemotaxonomic characteristics, this strain is proposed to represent a new species of a new genus Ferviditalea candida gen. nov., sp. nov. The type strain of the type species is SYSU GA230002T (=KCTC 25726T = GDMCC 1.4160T).

Methylobacterium nigriterrae sp. nov., isolated from black soil.

An aerobic, Gram-stain-negative, motile rod bacterium, designated as SYSU BS000021T, was isolated from a black soil sample in Harbin, Heilongjiang province, China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate belongs to the genus Methylobacterium, and showed the highest sequence similarity to Methylobacterium segetis KCTC 62267 T (98.51%) and Methylobacterium oxalidis DSM 24028 T (97.79%). Growth occurred at 20-37℃ (optimum, 28 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 0% (w/v) NaCl. Polar lipids comprised of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid and one unidentified polar lipid. The major cellular fatty acids (> 5%) were C18:0 and C18:1 ω7c and/or C18:1 ω6c. The predominant respiratory quinone was Q-10. The genomic G + C content was 68.36% based on the whole genome analysis. The average nucleotide identity (≤ 83.5%) and digital DNA-DNA hybridization (≤ 27.3%) values between strain SYSU BS000021T and other members of the genus Methylobacterium were all lower than the threshold values recommended for distinguishing novel prokaryotic species. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain SYSU BS000021T represents a novel species of the genus Methylobacterium, for which the name Methylobacterium nigriterrae sp. nov. is proposed. The type strain of the proposed novel species is SYSU BS000021T (= GDMCC 1.3814 T = KCTC 8051 T).

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Expression profiles and characterization of microRNAs responding to chitin in Arthrobotrys oligospora.

Extracellular proteases, such as chitinases secreted by Arthrobotrys oligospora (A. oligospora), play a crucial role in the process of nematode infection. However, post-transcriptional regulation of gene expression involving microRNAs (miRNAs) in A. oligospora remains scarcely described. Hereto, transcriptome sequencing was carried out to analyze the expression profiles of chitin-responsive miRNAs in A. oligospora. Based on the RNA-seq data, the differential expression of miRNAs (DEmiRNAs) in response to chitin was screened, identified and characterized in A. oligospora. Meanwhile, the potential target genes were predicted by the online tools miRanda and Targetscan, respectively. Furthermore, the interaction of DEmiRNA with it's target gene was validated by a dual-luciferase reporter assay system. Among 85 novel miRNAs identified, 25 miRNAs displayed significant differences in expression in A. oligospora in response to chitin. Gene Ontology (GO) analysis showed that the potential genes targeted by DEmiRNAs were enriched in the biological processes such as bio-degradation, extracellular components and cell cycle. KEGG analysis revealed that the target genes were mainly involved in Hippo, carbon and riboflavin metabolic pathway. Outstandingly, chitinase AOL_s00004g379, which is involved in the hydrolysis metabolic pathway of chitin, was confirmed to be a target gene of differential miR_70. These findings suggest that chitin-responsive miRNAs are involved in the regulation of cell proliferation, predator hyphae growth and chitinase expression through the mechanisms of post-transcriptional regulation, which provides a new perspective to the molecular mechanisms underlying miRNAs-mediated control of gene expression in A. oligospora.

Effects of the Pituitary-targeted Gland Axes on Hepatic Lipid Homeostasis in Endocrine-associated Fatty Liver Disease-A Concept Worth Revisiting.

Hepatic lipid homeostasis is not only essential for maintaining normal cellular and systemic metabolic function but is also closely related to the steatosis of the liver. The controversy over the nomenclature of non-alcoholic fatty liver disease (NAFLD) in the past three years has once again sparked in-depth discussions on the pathogenesis of this disease and its impact on systemic metabolism. Pituitary-targeted gland axes (PTGA), an important hormone-regulating system, are indispensable in lipid homeostasis. This review focuses on the roles of thyroid hormones, adrenal hormones, sex hormones, and their receptors in hepatic lipid homeostasis, and summarizes recent research on pituitary target gland axes-related drugs regulating hepatic lipid metabolism. It also calls on researchers and clinicians to recognize the concept of endocrine-associated fatty liver disease (EAFLD) and to re-examine human lipid metabolism from the macroscopic perspective of homeostatic balance.

STM1863, a Member of the DUFs Protein Family, Is Involved in Environmental Adaptation, Biofilm Formation, and Virulence in Salmonella Typhimurium.

Salmonella Typhimurium (STM) is an important zoonotic Gram-negative pathogen that can cause infection in a variety of livestock and poultry. Meanwhile, as an important foodborne pathogen, the bacterium can survive in various stressful environments and transmits through the fecal-oral route, posing a serious threat to global food safety. To investigate the roles of STM1863, a member of the DUFs protein family, involved in STM environmental adaptation, biofilm formation, and virulence. We analyzed the molecular characteristics of the protein encoded by STM1863 gene and examined intra- and extracellular expression levels of STM1863 gene in mouse macrophages. Furthermore, we constructed STM1863 gene deletion and complementation strains and determined its environmental adaptation under stressful conditions such as acid, alkali, high salt, bile salt, and oxidation. And the capacity of biofilm formation and pathogenicity of those strains were analyzed and compared. In addition, the interaction between the promoter of STM1863 gene and RcsB protein was analyzed using DNA gel electrophoresis migration assay (electrophoretic mobility shift assay [EMSA]). The experiments revealed that acid adaptability and biofilm formation ability of STM1863 gene deletion strain were significantly weakened compared with the parental and complementary strains. Moreover, the adhesion and invasion ability of STM1863 deletion strain to mouse macrophages was significantly decreased, while the median lethal dose (LD50) increased by 2.148-fold compared with the parental strain. In addition, EMSA confirmed that RcsB protein could bind to the promoter sequence of STM1863 gene, suggesting that the expression of STM1863 gene might be modulated by RcsB. The present study demonstrated for the first time that STM1863, a member of the DUFs protein family, is involved in the modulation of environmental adaptation, biofilm formation, and virulence.

MOCS, a novel classifier system integrated multimoics analysis refining molecular subtypes and prognosis for skin melanoma.

PURPOSE: The present investigation focuses on Skin Cutaneous Melanoma (SKCM), a melanocytic carcinoma characterized by marked aggression, significant heterogeneity, and a complex etiological background, factors which collectively contribute to the challenge in prognostic determinations. We defined a novel classifier system specifically tailored for SKCM based on multiomics. METHODS: We collected 423 SKCM samples with multi omics datasets to perform a consensus cluster analysis using 10 machine learning algorithms and verified in 2 independent cohorts. Clinical features, biological characteristics, immune infiltration pattern, therapeutic response and mutation landscape were compared between subtypes. RESULTS: Based on consensus clustering algorithms, we identified two Multi-Omics-Based-Cancer-Subtypes (MOCS) in SKCM in TCGA project and validated in GSE19234 and GSE65904 cohorts. MOCS2 emerged as a subtype with poor prognosis, characterized by a complex immune microenvironment, dysfunctional anti-tumor immune state, high cancer stemness index, and genomic instability. MOCS2 exhibited resistance to chemotherapy agents like erlotinib and sunitinib while sensitive to rapamycin, NSC87877, MG132, and FH355. Additionally, ELSPBP1 was identified as the target involving in glycolysis and M2 macrophage infiltration in SKCM. CONCLUSIONS: MOCS classification could stably predict prognosis of SKCM; patients with a high cancer stemness index combined with genomic instability may be predisposed to an immune exhaustion state.Communicated by Ramaswamy H. Sarma.

Design, Synthesis, Antifungal Activity, and 3D-QASR of Novel Oxime Ether-Containing Coumarin Derivatives as Potential Fungicides.

Structural modification of natural products is an effective approach for improving antifungal activity and has, therefore, been used extensively in the development of new agrochemical products. In this work, a series of novel coumarin derivatives containing oxime ether structures were designed, synthesized, and evaluated for antifungal activity. Some of the designed compounds exhibited promising antifungal activities against tested fungi, and compounds 4a, 4c, 5a, and 6b had EC50 values equivalent to those of commercial fungicides. Compound 6b was the most promising candidate fungicide against Rhizoctonia solani (EC50 = 0.46 µg/mL). In vivo antifungal bioassays suggested that compounds 5a and 6b could serve as novel agricultural antifungals. Furthermore, microscopy demonstrated that compound 6b induced the sprawling growth of hyphae, distorted the outline of cell walls, and reduced mitochondrial numbers. Additionally, the effects of the substituent steric, electrostatic, hydrophobic, and hydrogen-bond fields were elucidated using an accurate and reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) model. The results presented here will guide the discovery of potential novel fungicides for plant disease control in agriculture.

Chelatococcus albus sp. nov., a bacterium isolated from hot spring microbial mat.

A Gram-stain-negative, non-endospore-forming, motile, short rod-shaped strain, designated SYSU G07232T, was isolated from a hot spring microbial mat, sampled from Rehai National Park, Tengchong, Yunnan Province, south-western China. Strain SYSU G07232T grew at 25-50 °C (optimum, 37 °C), at pH 5.5-9.0 (optimum, pH 6.0) and tolerated NaCl concentrations up to 1.0 % (w/v). Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain SYSU G07232T showed closest genetic affinity with Chelatococcus daeguensis K106T. The genomic features and taxonomic status of this strain were determined through whole-genome sequencing and a polyphasic approach. The predominant quinone of this strain was Q-10. Major cellular fatty acids comprised C19 : 0 cyclo ω8c and summed feature 8. The whole-genome length of strain SYSU G07232T was 4.02 Mbp, and the DNA G+C content was 69.26 mol%. The average nucleotide identity (ANIm ≤84.85 % and ANIb ≤76.08  %) and digital DNA-DNA hybridization (≤ 21.9 %) values between strain SYSU G07232T and the reference species were lower than the threshold values recommended for distinguishing novel prokaryotic species. Thus, based on the provided phenotypic, phylogenetic, and genetic data, it is proposed that strain SYSU G07232T (=KCTC 8141T=GDMCC 1.4178T) be designated as representing a novel species within the genus Chelatococcus, named Chelatococcus albus sp. nov.