Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.144
Filter
1.
Angew Chem Int Ed Engl ; : e202409763, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954763

ABSTRACT

Developing non-platinum group metal catalysts for the sluggish hydrogen oxidation reaction (HOR) is critical for alkaline fuel cells. To date, Ni-based materials are the most promising candidates but still suffer from insufficient performance. Herein, we report an unconventional hcp/fcc Ni (u-hcp/fcc Ni) heteronanocrystal with multiple epitaxial hcp/fcc heterointerfaces and coherent twin boundaries, generating rugged surfaces with plenty of asymmetric convex sites. Systematic analyses discover that such convex sites enable the adsorption of *H in unusual bridge positions with weakened binding energy, circumventing the over-strong *H adsorption on traditional hollow positions, and simultaneously stabilizing interfacial *H2O. It thus synergistically optimizes the HOR thermodynamic process as well as reduces the kinetic barrier of the rate-determining Volmer step. Consequently, the developed u-hcp/fcc Ni exhibits the top-rank alkaline HOR activity with a mass activity of 40.6 mA mgNi-1 (6.3 times higher than fcc Ni control) together with superior stability and high CO-tolerance. These results provide a paradigm for designing high-performance catalysts by shifting the adsorption state of intermediates through configuring surface sites.

2.
BMC Med ; 22(1): 278, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956533

ABSTRACT

BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.


Subject(s)
Biomarkers , Dithiothreitol , Liver Cirrhosis , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/blood , Male , Middle Aged , Biomarkers/blood , Female , Adult , Aged , Oxidation-Reduction , ROC Curve , Cohort Studies , Oxidoreductases Acting on Sulfur Group Donors/blood , Proof of Concept Study
3.
Liver Int ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963299

ABSTRACT

BACKGROUND AND AIMS: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH. METHODS: We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. RESULTS: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region. CONCLUSION: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

5.
Poult Sci ; 103(9): 104065, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39043024

ABSTRACT

Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. The NGPV, a single-stranded DNA virus, is thought to be vertically transmitted. However, the mechanism of NGPV immune evasion remains unclear. In this study, we investigated the impact of NGPV infection on the Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in duck embryonic fibroblast (DEF) cells. Our findings demonstrate that NGPV infection stimulates the mRNA expression of cGAS but results in weak IFN-ß induction. NGPV impedes the expression of IFN-ß and downstream interferon-stimulated genes, thereby reducing the secretion of IFN-ß induced by interferon-stimulating DNA (ISD) and poly (I: C). RNA-seq results show that NGPV infection downregulates interferon mRNA expression while enhancing the mRNA expression of inflammatory factors. Additionally, the results of viral protein over-expression indicate that VP1 exhibits a remarkable ability to inhibit IFN-ß expression compared to other viral proteins. Results indicated that only the intact VP1 protein could inhibit the expression of IFN-ß, while the truncated proteins VP1U and VP2 do not possess such characteristics. The immunoprecipitation experiment showed that both VP1 and VP2 could interact with IRF7 protein, while VP1U does not. In summary, our findings indicate that NGPV infection impairs the host's innate immune response by potentially modulating the expression and secretion of interferons and interferon-stimulating factors via IRF7 molecules, which are regulated by the VP1 protein.

7.
Cardiovasc Diabetol ; 23(1): 202, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867293

ABSTRACT

The specific pathophysiological pathways through which diabetes exacerbates myocardial ischemia/reperfusion (I/R) injury remain unclear; however, dysregulation of immune and inflammatory cells, potentially driven by abnormalities in their number and function due to diabetes, may play a significant role. In the present investigation, we simulated myocardial I/R injury by inducing ischemia through ligation of the left anterior descending coronary artery in mice for 40 min, followed by reperfusion for 24 h. Previous studies have indicated that protein kinase Cß (PKCß) is upregulated under hyperglycemic conditions and is implicated in the development of various diabetic complications. The Y4 RNA fragment is identified as the predominant small RNA component present in the extracellular vesicles of cardio sphere-derived cells (CDCs), exhibiting notable anti-inflammatory properties in the contexts of myocardial infarction and cardiac hypertrophy. Our investigation revealed that the administration of Y4 RNA into the ventricular cavity of db/db mice following myocardial I/R injury markedly enhanced cardiac function. Furthermore, Y4 RNA was observed to facilitate M2 macrophage polarization and interleukin-10 secretion through the suppression of PKCß activation. The mechanism by which Y4 RNA affects PKCß by regulating macrophage activation within the inflammatory environment involves the inhibition of ERK1/2 phosphorylation In our study, the role of PKCß in regulating macrophage polarization during myocardial I/R injury was investigated through the use of PKCß knockout mice. Our findings indicate that PKCß plays a crucial role in modulating the inflammatory response associated with macrophage activation in db/db mice experiencing myocardial I/R, with a notable exacerbation of this response observed upon significant upregulation of PKCß expression. In vitro studies further elucidated the protective mechanism by which Y4 RNA modulates the PKCß/ERK1/2 signaling pathway to induce M2 macrophage activation. Overall, our findings suggest that Y4 RNA plays an anti-inflammatory role in diabetic I/R injury, suggesting a novel therapeutic approach for managing myocardial I/R injury in diabetic individuals.


Subject(s)
Disease Models, Animal , Macrophages , Mice, Inbred C57BL , Myocardial Reperfusion Injury , Protein Kinase C beta , Signal Transduction , Animals , Protein Kinase C beta/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/enzymology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/prevention & control , Myocardial Reperfusion Injury/genetics , Macrophages/metabolism , Macrophages/enzymology , Male , Interleukin-10/metabolism , Interleukin-10/genetics , Mice , Diabetic Cardiomyopathies/enzymology , Diabetic Cardiomyopathies/pathology , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/etiology , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/physiopathology , Cells, Cultured , Phenotype , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/pathology , Myocytes, Cardiac/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Macrophage Activation , Mitogen-Activated Protein Kinase 1/metabolism , Ventricular Function, Left , Phosphorylation
8.
STAR Protoc ; 5(2): 103108, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38824637

ABSTRACT

Changes in telomerase activity and telomere length contribute to aging-related decline. Investigating telomerase in aging models provides insights into related pathologies. Here, we present a protocol to detect telomerase activity in adult mouse hippocampal neural progenitor cells using the telomeric repeat amplification protocol assay. We describe steps for isolating and expanding aged mouse hippocampal neural progenitor cells (NPCs) and assessing telomerase using a non-radioactive technique. The protocol emphasizes the significance of understanding telomerase activity in NPCs for neurogenesis and age-related diseases.


Subject(s)
Hippocampus , Neural Stem Cells , Telomerase , Telomere , Animals , Telomerase/metabolism , Telomerase/genetics , Mice , Neural Stem Cells/metabolism , Neural Stem Cells/cytology , Hippocampus/cytology , Hippocampus/metabolism , Telomere/metabolism
9.
Environ Sci Technol ; 58(28): 12498-12508, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38900106

ABSTRACT

Appropriate mixed carbon sources have great potential to enhance denitrification efficiency and reduce operational costs in municipal wastewater treatment plants (WWTPs). However, traditional methods struggle to efficiently select the optimal mixture due to the variety of compositions. Herein, we developed a machine learning-assisted high-throughput method enabling WWTPs to rapidly identify and optimize mixed carbon sources. Taking a local WWTP as an example, a mixed carbon source denitrification data set was established via a high-throughput method and employed to train a machine learning model. The composition of carbon sources and the types of inoculated sludge served as input variables. The XGBoost algorithm was employed to predict the total nitrogen removal rate and microbial growth, thereby aiding in the assessment of the denitrification potential. The predicted carbon sources exhibited an enhanced denitrification potential over single carbon sources in both kinetic experiments and long-term reactor operations. Model feature analysis shows that the cumulative effect and interaction among individual carbon sources in a mixture significantly enhance the overall denitrification potential. Metagenomic analysis reveals that the mixed carbon sources increased the diversity and complexity of denitrifying bacterial ecological networks in WWTPs. This work offers an efficient method for WWTPs to optimize mixed carbon source compositions and provides new insights into the mechanism behind enhanced denitrification under a supply of multiple carbon sources.


Subject(s)
Carbon , Denitrification , Machine Learning , Wastewater/chemistry , Nitrogen , Waste Disposal, Fluid/methods , Sewage/microbiology
10.
Anim Reprod Sci ; 267: 107540, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38908171

ABSTRACT

In poultry reproduction, the decline of ovarian function due to aging is related to dysfunction of mitochondria exacerbated by a reduction in antioxidant capacity, ultimately leading to follicle atresia and decreased egg production. However, the mechanisms of mitochondrial dysfunction in the chicken ovary in aging have remained to be understood. Hence, this study aims to investigate the effects of aging on mitochondrial function and cellular homeostasis. We collect ovarian tissue, small white follicles (SWF), large white follicles (LWF), and small yellow follicles (SYF) from three different laying periods of hens. The transmission electron microscopy (TEM) results showed that mitochondrial damage occurred in ovarian tissue during the late laying period (LP), characterized by structural swelling, scattered mitochondrial cristae, and an increase in the vacuoles. At the same time, with age, the synthesis of steroid hormones in the ovaries and follicular tissues is reduced. The levels of autophagy and cell apoptosis in ovarian tissues were both increased in the LP. In addition, aging adversely impacts mitochondrial function, leading to a decrease in mitochondrial unfolded protein response (UPRmt) functions. This study will expand the knowledge about regressing ovarian aging in hens and increasing egg production in older layers for poultry production.


Subject(s)
Aging , Chickens , Homeostasis , Mitochondria , Ovary , Animals , Female , Chickens/physiology , Mitochondria/metabolism , Ovary/metabolism , Apoptosis , Steroids/biosynthesis , Steroids/metabolism
11.
Genome Biol ; 25(1): 131, 2024 05 21.
Article in English | MEDLINE | ID: mdl-38773623

ABSTRACT

BACKGROUND: High-efficiency prime editing (PE) is desirable for precise genome manipulation. The activity of mammalian PE systems can be largely improved by inhibiting DNA mismatch repair by coexpressing a dominant-negative variant of MLH1. However, this strategy has not been widely used for PE optimization in plants, possibly because of its less conspicuous effects and inconsistent performance at different sites. RESULTS: We show that direct RNAi knockdown of OsMLH1 in an ePE5c system increases the efficiency of our most recently updated PE tool by 1.30- to 2.11-fold in stably transformed rice cells, resulting in as many as 85.42% homozygous mutants in the T0 generation. The high specificity of ePE5c is revealed by whole-genome sequencing. To overcome the partial sterility induced by OsMLH1 knockdown of ePE5c, a conditional excision system is introduced to remove the RNAi module by Cre-mediated site-specific recombination. Using a simple approach of enriching excision events, we generate 100% RNAi module-free plants in the T0 generation. The increase in efficiency due to OsMLH1 knockdown is maintained in the excised plants, whose fertility is not impaired. CONCLUSIONS: This study provides a safe and reliable plant PE optimization strategy for improving editing efficiency without disturbing plant development via transient MMR inhibition with an excisable RNAi module of MLH1.


Subject(s)
Gene Editing , Oryza , Plant Proteins , Oryza/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Fertility/genetics , Gene Knockdown Techniques , MutL Protein Homolog 1/genetics , RNA Interference , CRISPR-Cas Systems , Plants, Genetically Modified
12.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2299-2307, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812130

ABSTRACT

In the traditional Chinese medicine(TCM) manufacturing industry, quality control determines the safety, effectiveness, and quality stability of the final product. The traditional quality control method generally carries out sampling off-line testing of drugs after the end of the batch production, which is incomprehensive, and it fails to find the problems in the production process in time. Process analysis technology(PAT) uses process testing, mathematical modeling, data analysis, and other technologies to collect, analyze, feedback, control, and continuously improve the critical quality attributes(CQA) in all aspects of the production of TCM preparations in real time. The application of PAT in the TCM manufacturing industry is one of the research hotspots in recent years, which has the advantages of real-time, systematic, non-destructive, green, and rapid detection for the production quality control of TCM preparations. It can effectively ensure the stability of the quality of TCM preparations, improve production efficiency, and play a key role in the study of the quantity and quality transfer law of TCM. Commonly used PAT includes near-infrared spectroscopy, Raman spectroscopy, online microwave, etc. In addition, the establishment of an online detection model by PAT is the key basic work to realize intelligent manufacturing in TCM production. Obtaining real-time online detection data through PAT and establishing a closed-loop control model on this basis are a key common technical difficulty in the industry. This paper adopted systematic literature analysis to summarize the relevant Chinese and foreign literature, policies and regulations, and production applications, and it introduced the development trend and practical application of PAT, so as to provide references for accelerating the application of PAT in the TCM manufacturing industry, the intelligent transformation and upgrading, and high-quality development of the TCM industry.


Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Quality Control , Medicine, Chinese Traditional/standards , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/standards , Drugs, Chinese Herbal/analysis , Technology, Pharmaceutical/methods , Technology, Pharmaceutical/standards , Drug Industry/standards
13.
Cell Mol Gastroenterol Hepatol ; 18(2): 101354, 2024.
Article in English | MEDLINE | ID: mdl-38729522

ABSTRACT

BACKGROUND & AIMS: Dysfunction of the intestinal epithelial barrier comprising the junctional complex of tight junctions and adherent junctions leads to increased intestinal permeability, which is a major cause of uncontrolled inflammation related to inflammatory bowel disease (IBD). The NAD+-dependent deacetylase SIRT1 is implicated in inflammation and the pathologic process of IBD. We aimed to elucidate the protective role and underlying mechanism of SIRT1 in cell-cell junction and intestinal epithelial integrity. METHODS: The correlation of SIRT1 expression and human IBD was analyzed by GEO or immunohistochemical analyses. BK5.mSIRT1 transgenic mice and wild-type mice were given dextran sodium sulfate (DSS) and the manifestation of colitis-related phenotypes was analyzed. Intestinal permeability was measured by FITC-dextran and cytokines expression was analyzed by quantitative polymerase chain reaction. The expression of the cell junction-related proteins in DSS-treated or SIRT1-knockdown Caco2 or HCT116 cells was analyzed by Western blotting. The effects of nicotinamide mononucleotide in DSS-induced mice colitis were investigated. Correlations of the SIRT1-ß-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway with human IBD samples were analyzed. RESULTS: Reduced SIRT1 expression is associated with human IBD specimens. SIRT1 transgenic mice exhibit much-reduced manifestations of DSS-induced colitis. The activation of SIRT1 by nicotinamide mononucleotide bolsters intestinal epithelial barrier function and ameliorates DSS-induced colitis in mice. Mechanistically, DSS downregulates SiRT1 expression, leading to destabilization of ß-TrCP1 and upregulation of Snail1, accompanied by reduced expression of E-cadherin, Occludin, and Claudin-1, consequently resulting in increased epithelial permeability and inflammation. The deregulated SIRT1-ß-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway correlates with human IBD. CONCLUSIONS: SIRT1 is pivotal in maintaining the intestinal epithelial barrier integrity via modulation of the ß-TrCP1-Snail1-E-cadhein/Occludin/Claudin-1 pathway.


Subject(s)
Colitis , Intestinal Mucosa , Sirtuin 1 , Snail Family Transcription Factors , beta-Transducin Repeat-Containing Proteins , Animals , Humans , Male , Mice , beta-Transducin Repeat-Containing Proteins/metabolism , Caco-2 Cells , Cadherins/metabolism , Cadherins/genetics , Colitis/chemically induced , Colitis/pathology , Colitis/metabolism , Dextran Sulfate/toxicity , Disease Models, Animal , Inflammatory Bowel Diseases/pathology , Inflammatory Bowel Diseases/metabolism , Intestinal Mucosa/pathology , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Mice, Transgenic , Permeability , Sirtuin 1/metabolism , Sirtuin 1/genetics , Snail Family Transcription Factors/metabolism , Snail Family Transcription Factors/genetics , Tight Junctions/metabolism , Tight Junctions/pathology
14.
Sci Rep ; 14(1): 10570, 2024 05 08.
Article in English | MEDLINE | ID: mdl-38719931

ABSTRACT

The coexistence of sympatric species with similar ecological niches has been a central issue in ecology. Clarifying the daily activity patterns of sympatric wild ungulates can help understand their temporal niche differentiation and the mechanisms of coexistence, providing information for their conservation. The Baotianman National Nature Reserve in northern China is rich in wild ungulates, but little is known about the daily activity patterns of wild ungulates in the area, making it difficult to develop effective conservation strategies. We studied five representative wild ungulates (i.e. forest musk deer, Chinese goral, Reeve's muntjac, Siberian roe deer, and wild boar) of the region using camera-trapping data, focusing on the seasonal daily activity patterns and effects of seasonal grazing of domestic sheep, to reveal their coexistence based on temporal ecological niche differentiation. Comparative analyses of the seasonal daily activity showed that forest musk deer exhibited a single-peak activity in the warm season. Other ungulates exhibited multipeak activity. All five ungulates differed significantly in daily activity patterns. Notably, wild boar and Reeve's muntjac showed high overlap coefficients between the cold and warm seasons. In both cold and warm seasons, the five wild ungulates and domestic sheep displayed low overlap in their daily activity rhythms potentially indicating temporal ecological niche differentiation. The results suggest that temporal isolation might be a strategy for wild ungulates to avoid domestic sheep and reduce interspecific competition, and that temporal ecological niche differentiation potentially promoted the coexistence among the studied sympatric ungulates. This understanding may provide new insights for the development of targeted conservation strategies.


Subject(s)
Animals, Wild , Deer , Ecosystem , Seasons , Sympatry , Animals , Deer/physiology , Animals, Wild/physiology , China , Sheep/physiology
15.
Small ; : e2401159, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38716681

ABSTRACT

Defects can introduce atomic structural modulation and tailor performance of materials. Herein, it demonstrates that semiconductor WO3 with inert electrocatalytic behavior can be activated through defect-induced tensile strains. Structural characterizations reveal that when simply treated in Ar/H2 atmosphere, oxygen vacancies will generate in WO3 and cause defective structures. Stacking faults are found in defects, thus modulating electronic structure and transforming electrocatalytic-inert WO3 into highly active electrocatalysts. Density functional theory (DFT) calculations are performed to calculate *H adsorption energies on various WOx surfaces, revealing the oxygen vacancy composition and strain predicted to optimize the catalytic activity of hydrogen evolution reaction (HER). Such defective tungsten oxides can be integrated into commercial proton exchange membrane (PEM) electrolyser with comparable performance toward Pt-based PEM. This work demonstrates defective metal oxides as promising non-noble metal catalysts for commercial PEM green-hydrogen generation.

16.
Nat Commun ; 15(1): 4066, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744885

ABSTRACT

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.


Subject(s)
Archaea , Genome, Archaeal , Hot Springs , Metagenome , Metagenomics , Phylogeny , Hot Springs/microbiology , Archaea/genetics , Archaea/classification , China , Metagenomics/methods , Biodiversity , Hydrogen-Ion Concentration , Sulfur/metabolism , Temperature , Ecosystem
17.
Front Bioeng Biotechnol ; 12: 1394177, 2024.
Article in English | MEDLINE | ID: mdl-38745845

ABSTRACT

Body sizes and head anatomical characteristics play the major role in the head injuries sustained by vulnerable road users (VRU) in traffic accidents. In this study, in order to study the influence mechanism of body sizes and head anatomical characteristics on head injury, we used age, gender, height, and Body Mass Index (BMI) as characteristic parameters to develop the personalized human body multi-rigid body (MB) models and head finite element (FE) models. Next, using simulation calculations, we developed the VRU head injury dataset based on the personalized models. In the dataset, the dependent variables were the degree of head injury and the brain tissue von Mises value, while the independent variables were height, BMI, age, gender, traffic participation status, and vehicle speed. The statistical results of the dataset show that the von Mises value of VRU brain tissue during collision ranges from 4.4 kPa to 46.9 kPa at speeds between 20 and 60 km/h. The effects of anatomical characteristics on head injury include: the risk of a more serious head injury of VRU rises with age; VRU with higher BMIs has less head injury in collision accidents; height has very erratic and nonlinear impacts on the von Mises values of the VRU's brain tissue; and the severity of head injury is not significantly influenced by VRU's gender. Furthermore, we developed the classification prediction models of head injury degree and the regression prediction models of head injury response parameter by applying eight different data mining algorithms to this dataset. The classification prediction models have the best accuracy of 0.89 and the best R2 value of 0.85 for the regression prediction models.

18.
J Hematol ; 13(1-2): 12-22, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38644985

ABSTRACT

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

19.
Adv Sci (Weinh) ; 11(20): e2306059, 2024 May.
Article in English | MEDLINE | ID: mdl-38528665

ABSTRACT

Tumor-initiating cells (TICs) resilience and an immunosuppressive microenvironment are aggressive oncogenic phenotypes that contribute to unsatisfactory long-term outcomes in lung adenocarcinoma (LUAD) patients. The molecular mechanisms mediating the interaction between TICs and immune tolerance have not been elucidated. The role of Galectin-9 in oncogenesis and immunosuppressive microenvironment is still unknown. This study explored the potential role of galectin-9 in TIC regulation and immune modulation in LUAD. The results show that galectin-9 supports TIC properties in LUAD. Co-culture of patient-derived organoids and matched peripheral blood mononuclear cells showed that tumor-secreted galectin-9 suppressed T cell cytotoxicity and induced regulatory T cells (Tregs). Clinically, galectin-9 is upregulated in human LUAD. High expression of galectin-9 predicted poor recurrence-free survival and correlated with high levels of Treg infiltration. LGALS9, the gene encoding galectin-9, is found to be transcriptionally regulated by the nuclear factor of activated T cells 2 (NFATc2), a previously reported TIC regulator, via in silico prediction and luciferase reporter assays. Overall, the results suggest that the NFATc2/galectin-9 axis plays a dual role in TIC regulation and immune suppression.


Subject(s)
Adenocarcinoma of Lung , Galectins , Lung Neoplasms , NFATC Transcription Factors , Neoplastic Stem Cells , Humans , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , Cell Line, Tumor , Galectins/genetics , Galectins/metabolism , Galectins/immunology , Lung Neoplasms/immunology , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Neoplastic Stem Cells/immunology , Neoplastic Stem Cells/metabolism , NFATC Transcription Factors/metabolism , NFATC Transcription Factors/genetics , Phenotype , Tumor Microenvironment
20.
Protein Cell ; 15(6): 419-440, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38437016

ABSTRACT

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression. However, targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail. Here, we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy. ETBF, albeit at low biomass, secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance. Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein. NOD1 was highly expressed on ALDH+ breast cancer stem cells (BCSCs) and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation, thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs. NOD1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.


Subject(s)
Bacteroides fragilis , Breast Neoplasms , Drug Resistance, Neoplasm , Neoplastic Stem Cells , Nod1 Signaling Adaptor Protein , Humans , Nod1 Signaling Adaptor Protein/metabolism , Nod1 Signaling Adaptor Protein/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/microbiology , Breast Neoplasms/genetics , Female , Bacteroides fragilis/metabolism , Bacteroides fragilis/genetics , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Bacterial Toxins/metabolism , Bacterial Toxins/genetics , Animals , Mice , Cell Line, Tumor , Metalloendopeptidases
SELECTION OF CITATIONS
SEARCH DETAIL