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1.
Sci Total Environ ; 932: 173038, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38719055

ABSTRACT

Despite global concerns about metal(loid)s in atmospheric particulate matter (PM), the presence of metal(loid) resistance genes (MRGs) in PM remains unknown. Therefore, we conducted a comprehensive investigation of the metal(loid)s and associated MRGs in PMs in two seasons (summer and winter) in Xiamen, China. According to the geoaccumulation index (Igeo), most metal(loid)s, except for V and Mn, exhibited enrichment in PM, suggesting potential anthropogenic sources. By employing Positive Matrix Factorization (PMF) model, utilizing a dataset encompassing both total and bioaccessible metal(loid)s, along with backward trajectory simulations, traffic emissions were determined to be the primary potential contributor of metal(loid)s in summer, whereas coal combustion was observed to have a dominant contribution in winter. The major contributor to the carcinogenic risk of metal(loid)s in both summer and winter was predominantly attributed to coal combustion, which serves as the main source of bioaccessible Cr. Bacterial communities within PMs showed lower diversity and network complexity in summer than in winter, with Pseudomonadales being the dominant order. Abundant MRGs, including the As(III) S-adenosylmethionine methyltransferase gene (arsM), Cu(I)-translocating P-type ATPase gene (copA), Zn(II)/Cd(II)/Pb(II)-translocating P-type ATPase gene (zntA), and Zn(II)-translocating P-type ATPase gene (ziaA), were detected within the PMs. Seasonal variations were observed for the metal(loid) concentration, bacterial community structure, and MRG abundance. The bacterial community composition and MRG abundance within PMs were primarily influenced by temperature, rather than metal(loid)s. This research offers novel perspectives on the occurrence of metal(loid)s and MRGs in PMs, thereby contributing to the control of air pollution.


Subject(s)
Air Pollutants , Environmental Monitoring , Particulate Matter , Particulate Matter/analysis , Air Pollutants/analysis , China , Metals/analysis , Seasons , Atmosphere/chemistry
2.
Environ Int ; 187: 108688, 2024 May.
Article in English | MEDLINE | ID: mdl-38685158

ABSTRACT

The phyllosphere, particularly the leaf surface of plants, harbors a diverse range of microbiomes that play a vital role in the functioning of terrestrial ecosystems. However, our understanding of microbial successions and their impact on functional genes during plant community development is limited. In this study, considering core and satellite microbial taxa, we characterized the phyllosphere microbiome and functional genes in various microhabitats (i.e., leaf litter, moss and plant leaves) across the succession of a plant community in a low-altitude glacier foreland. Our findings indicate that phyllosphere microbiomes and associated ecosystem stability increase during the succession of the plant community. The abundance of core taxa increased with plant community succession and was primarily governed by deterministic processes. In contrast, satellite taxa abundance decreased during plant community succession and was mainly governed by stochastic processes. The abundance of microbial functional genes (such as C, N, and P hydrolysis and fixation) in plant leaves generally increased during the plant community succession. However, in leaf litter and moss leaves, only a subset of functional genes (e.g., C fixation and degradation, and P mineralization) showed a tendency to increase with plant community succession. Ultimately, the community of both core and satellite taxa collaboratively influenced the characteristics of phyllosphere nutrient-cycling genes, leading to the diverse profiles and fluctuating abundance of various functional genes during plant community succession. These findings offer valuable insights into the phyllosphere microbiome and plant-microbe interactions during plant community development, advancing our understanding of the succession and functional significance of the phyllosphere microbial community.


Subject(s)
Microbiota , Plant Leaves , Plant Leaves/microbiology , Ecosystem , Plants/microbiology , Plant Development
3.
Sci Rep ; 14(1): 7645, 2024 04 01.
Article in English | MEDLINE | ID: mdl-38561361

ABSTRACT

Remimazolam, a novel intravenous anesthetic, has been proven to be safe and efficacious in the gastroscopy setting among the elderly. However, reports comparing the effectiveness and safety of using equivalent doses of remimazolam with propofol have not been seen. The aim of this study was to compare the sedation efficacy and safety of the 95% effective doses (ED95) of remimazolam versus propofol combined with sufentanil in the gastroscopy setting among the elderly. In the first step of this two-step study, a modified up-and-down method was used to calculate the ED95 of remimazolam and propofol when combined with 0.1 µg/kg sufentanil in inhibiting body movement of elderly patients undergoing gastroscopy. In the second step, ED95 of both agents calculated in the first step were administered, endpoints of efficacy, safety, and incidence of adverse events were compared. A total of 46 individuals completed the first step. The ED95 of remimazolam was 0.163 mg/kg (95% CI 0.160-0.170 mg/kg), and that of propofol was 1.042 mg/kg (95% CI 1.007-1.112 mg/kg). In the second step, 240 patients completed the trial. The anesthetic effective rates of the remimazolam group and the propofol group were 78% and 83%, respectively, with no statistical difference (P = 0.312). Patients in the remimazolam group had more stable circulatory functions (P < 0.0001) and a lower incidence of pain on injection (3.3% vs. 19.5%, P < 0.0001). The incidence of hypotension was low in the remimazolam versus propofol group (15.6% vs. 39.0%, P < 0.0001). Overall adverse event was low in the remimazolam versus propofol group (21.3% vs. 62.7%, P < 0.0001).In this study, we found that when anesthesia was administered to elderly gastroscopy patients based on 95% effective doses of remimazolam and propofol, remimazolam was as effective as propofol, but was safer with a lower incidence of adverse events.Study registration: Chinese Clinical Trial Registry, ChiCTR2000034234. Registered 29/06/2020, https://www.chictr.org.cn .


Subject(s)
Anesthesia , Propofol , Aged , Humans , Benzodiazepines , Gastroscopy , Propofol/adverse effects , Sufentanil
4.
Clin Exp Pharmacol Physiol ; 51(6): e13859, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643975

ABSTRACT

Previous study has demonstrated that the Dietary Inflammation Index (DII) played a role in the risk of inflammatory bowel disease (IBD), however, the prevalence and risk factors for IBD are distinct across locations and groups, and therefore, the findings are debatable and warrant further investigation. A total of 4363 participants were calculated in the National Health and Nutrition Examination Survey (NHANES) 2009 to 2010, of whom 1.21% self-reported a history of IBD. DII values were performed as a good predictor of dietary inflammation based on data from two 24-h dietary reviews in the NHANES database. Comparing the multifarious effects along with variations of the whole population by grouping populations according to DII quartiles, dietary inflammation levels increased progressively from DII quartile 1(Q1) to quartile 4(Q4). The association between DII and IBD was tested with multi-variable logistic regression models, subgroup analyses and weighted generalized additive models. Participants in the Q4 group showed the highest levels of C-reactive protein and reduced haemoglobin and albumin levels. Logistic regression confirmed the odds ratios (95% confidence intervals) of IBD for DII were 0.99 (0.86, 1.15), 0.97 (0.84, 1.13) and 0.80 (0.66, 0.98) in models 1, 2 and 3, respectively. The negative correlation between DII and IBD among United States adults from the NHANES database became increasingly apparent as covariates were adjusted. Subgroup analyses and smoothed curve fitting confirmed the inverse results. The study revealed that DII was correlated with the overall physical well-being of participants. However, there was no significant association between DII and IBD.


Subject(s)
Diet , Inflammation , Inflammatory Bowel Diseases , Nutrition Surveys , Humans , Inflammatory Bowel Diseases/epidemiology , Male , Female , Adult , Inflammation/epidemiology , Inflammation/blood , Diet/adverse effects , Middle Aged , Risk Factors , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , United States/epidemiology
5.
Chin J Integr Med ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676827

ABSTRACT

OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 107 CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- ß -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-ß-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS: CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.

6.
J Am Soc Nephrol ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38687867

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with high mortality. Inflammation plays a key role in the pathophysiology of AKI. Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of the inflammatory and immune response, but its role in AKI remains unclear. METHODS: We explored the role of lncRNA Neat1 in (1) a cross-sectional and a longitudinal cohort of AKI in human; (2) three murine models of septic and aseptic AKI and (3) cultured C1.1 mouse kidney tubular cells. RESULTS: In human, hospitalized patients with AKI (n=66) demonstrated significantly increased lncRNA Neat1 levels in urinary sediment cells and buffy coat versus control participants (n=152) from a primary care clinic; and among 6 kidney transplant recipients, Neat1 levels were highest immediately after transplant surgery followed by a prompt decline to normal levels in parallel with recovery of kidney function. In mice with AKI induced by sepsis (via LPS injection or cecal ligation and puncture) and renal ischemia-reperfusion, kidney tubular Neat1 was increased versus sham-operated mice. Knockdown of Neat1 in the kidney using short hairpin RNA preserved kidney function, suppressed overexpression of the AKI biomarker NGAL, leukocyte infiltration and both intrarenal and systemic inflammatory cytokines IL-6, CCL-2 and IL-1ß. In LPS-treated C1.1 cells, Neat1 was overexpressed via TLR4/NF-κB signaling, and translocated from the cell nucleus into the cytoplasm where it promoted activation of NLRP3 inflammasomes via binding with the scaffold protein Rack1. Silencing Neat1 ameliorated LPS-induced cell inflammation, whereas its overexpression upregulated IL-6 and CCL-2 expression even without LPS stimulation. CONCLUSIONS: Our findings demonstrate a pathogenic role of Neat1 induction in human and mice during AKI with alleviation of kidney injury in 3 experimental models of septic and aseptic AKI after knockdown of Neat1. LPS/TLR4-induced Neat1 overexpression in tubular epithelial cells increases the inflammatory response by binding with the scaffold protein, Rack1, to activate NLRP3 inflammasomes.

7.
Elife ; 132024 Apr 30.
Article in English | MEDLINE | ID: mdl-38687676

ABSTRACT

Regulated hydrolysis of the phosphoinositide phosphatidylinositol(4,5)-bis-phosphate to diacylglycerol and inositol-1,4,5-P3 defines a major eukaryotic pathway for translation of extracellular cues to intracellular signaling circuits. Members of the lipid-activated protein kinase C isoenzyme family (PKCs) play central roles in this signaling circuit. One of the regulatory mechanisms employed to downregulate stimulated PKC activity is via a proteasome-dependent degradation pathway that is potentiated by peptidyl-prolyl isomerase Pin1. Here, we show that contrary to prevailing models, Pin1 does not regulate conventional PKC isoforms α and ßII via a canonical cis-trans isomerization of the peptidyl-prolyl bond. Rather, Pin1 acts as a PKC binding partner that controls PKC activity via sequestration of the C-terminal tail of the kinase. The high-resolution structure of full-length Pin1 complexed to the C-terminal tail of PKCßII reveals that a novel bivalent interaction mode underlies the non-catalytic mode of Pin1 action. Specifically, Pin1 adopts a conformation in which it uses the WW and PPIase domains to engage two conserved phosphorylated PKC motifs, the turn motif and hydrophobic motif, respectively. Hydrophobic motif is a non-canonical Pin1-interacting element. The structural information combined with the results of extensive binding studies and experiments in cultured cells suggest that non-catalytic mechanisms represent unappreciated modes of Pin1-mediated regulation of AGC kinases and other key enzymes/substrates.


Subject(s)
NIMA-Interacting Peptidylprolyl Isomerase , Protein Binding , NIMA-Interacting Peptidylprolyl Isomerase/metabolism , NIMA-Interacting Peptidylprolyl Isomerase/chemistry , NIMA-Interacting Peptidylprolyl Isomerase/genetics , Humans , Protein Kinase C/metabolism , Protein Kinase C/chemistry , Protein Kinase C/genetics , Protein Conformation
8.
Arch Toxicol ; 98(5): 1297-1310, 2024 May.
Article in English | MEDLINE | ID: mdl-38498160

ABSTRACT

Lung injury has been a serious medical problem that requires new therapeutic approaches and biomarkers. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) that exist widely in eukaryotes. CircRNAs are single-stranded RNAs that form covalently closed loops. CircRNAs are significant gene regulators that have a role in the development, progression, and therapy of lung injury by controlling transcription, translating into protein, and sponging microRNAs (miRNAs) and proteins. Although the study of circRNAs in lung injury caused by pulmonary toxicants is just beginning, several studies have revealed their expression patterns. The function that circRNAs perform in relation to pulmonary toxicants (severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), drug abuse, PM2.5, and cigarette smoke) is the main topic of this review. A variety of circRNAs can serve as potential biomarkers of lung injury. In this review, the biogenesis, properties, and biological functions of circRNAs were concluded, and the relationship between circRNAs and pulmonary toxicants was discussed. It is expected that the new ideas and potential treatment targets that circRNAs provide would be beneficial to research into the molecular mechanisms behind lung injury.


Subject(s)
Lung Injury , MicroRNAs , Humans , RNA, Circular/genetics , Lung Injury/chemically induced , Lung Injury/genetics , Lung Injury/therapy , Lung/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers/metabolism
9.
Phytomedicine ; 128: 155347, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38493717

ABSTRACT

BACKGROUND: Bile acid (BA) enterohepatic circulation disorders are a main feature of chronic cholestatic diseases. Promoting BA metabolism is thus a potential method of improving enterohepatic circulation disorders, and treat enterohepatic inflammation, oxidative stress and fibrosis due to cholestasis. PURPOSE: To investigate the effect of JiaGaSongTang (JGST) and its blood-absorbed ingredient 6-gingerol on α-naphthylisothiocyanate (ANIT)-induced chronic cholestasis, as well as elucidate the underlying regulatory mechanism. METHODS: Chronic cholestasis was induced in mice via subcutaneous injection of ANIT (50 mg/kg) every other day for 14 d. Treatment groups were administered JGST orally daily. Damage to the liver and intestine was observed using histopathological techniques. Biochemical techniques were employed to assess total BA (TBA) levels in the serum, liver, and ileum samples. Liquid chromatograph-mass spectrometry/mass spectrometry (LC-MS/MS) was used to analyze fecal BA components. Bioinformatic methods were adopted to screen the core targets and pathways. The blood-absorbed ingredients of JGST were scrutinized via LC-MS/MS. The effects of the major JGST ingredients on farnesoid X receptor (FXR) transactivation were validated using dual luciferase reporter genes. Lastly, the effects of the FXR inhibitor, DY268, on JGST and 6-gingerol pharmacodynamics were observed at the cellular and animal levels. RESULTS: JGST ameliorated pathological impairments in the liver and intestine, diminishing TBA levels in the serum, liver and gut. Fecal BA profiling revealed that JGST enhanced the excretion of toxic BA constituents, including deoxycholic acid. Bioinformatic analyses indicated that JGST engaged in anti-inflammatory mechanisms, attenuating collagen accumulation, and orchestrating BA metabolism via interactions with FXR and other pertinent targets. LC-MS/MS analysis identified six ingredients absorbed to the bloodstream, including 6-gingerol. Surface plasmon resonance (SPR) and dual luciferase reporter gene assays confirmed the abilities of 6-gingerol to bind to FXR and activate its transactivation. Ultimately, in both cellular and animal models, the therapeutic efficacy of JGST and 6-gingerol in chronic cholestasis was attenuated in the presence of FXR inhibitors. CONCLUSION: The findings, for the first time, demonstrated that 6-gingerol, a blood-absorbed ingredient of JGST, can activate FXR to affect BA metabolism, and thereby attenuate ANIT-induced liver and intestinal injury in chronic cholestasis mice model via inhibition of inflammation, oxidative stress, and liver fibrosis, in part in a FXR-dependent mechanism.


Subject(s)
1-Naphthylisothiocyanate , Bile Acids and Salts , Catechols , Cholestasis , Fatty Alcohols , Liver , Receptors, Cytoplasmic and Nuclear , Animals , Bile Acids and Salts/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Cholestasis/drug therapy , Cholestasis/metabolism , Male , Mice , Catechols/pharmacology , Liver/drug effects , Liver/metabolism , Fatty Alcohols/pharmacology , Drugs, Chinese Herbal/pharmacology , Mice, Inbred C57BL , Humans , Chronic Disease , Disease Models, Animal
10.
New Phytol ; 242(5): 2353-2368, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38515228

ABSTRACT

Evolutionary radiation, a pivotal aspect of macroevolution, offers valuable insights into evolutionary processes. The genus Pinus is the largest genus in conifers with c . 90% of the extant species emerged in the Miocene, which signifies a case of rapid diversification. Despite this remarkable history, our understanding of the mechanisms driving radiation within this expansive genus has remained limited. Using exome capture sequencing and a fossil-calibrated phylogeny, we investigated the divergence history, niche diversification, and introgression among 13 closely related Eurasian species spanning climate zones from the tropics to the boreal Arctic. We detected complex introgression among lineages in subsection Pinus at all stages of the phylogeny. Despite this widespread gene exchange, each species maintained its genetic identity and showed clear niche differentiation. Demographic analysis unveiled distinct population histories among these species, which further influenced the nucleotide diversity and efficacy of purifying and positive selection in each species. Our findings suggest that radiation in the Eurasian pines was likely fueled by interspecific recombination and further reinforced by their adaptation to distinct environments. Our study highlights the constraints and opportunities for evolutionary change, and the expectations of future adaptation in response to environmental changes in different lineages.


Subject(s)
Gene Flow , Phylogeny , Pinus , Pinus/genetics , Pinus/radiation effects , Biological Evolution , Genetic Variation , Species Specificity , Europe , Genetic Speciation
11.
Environ Sci Technol ; 58(10): 4476-4486, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38382547

ABSTRACT

Antibiotic resistance genes (ARGs) are ancient but have become a modern critical threat to health. Gut microbiota, a dynamic reservoir for ARGs, transfer resistance between individuals. Surveillance of the antibiotic resistome in the gut during different host growth phases is critical to understanding the dynamics of the resistome in this ecosystem. Herein, we disentangled the ARG profiles and the dynamic mechanism of ARGs in the egg and adult phases of Tetramorium caespitum. Experimental results showed a remarkable difference in both gut microbiota and gut resistome with the development of T. caespitum. Meta-based metagenomic results of gut microbiota indicated the generalizability of gut antibiotic resistome dynamics during host development. By using Raman spectroscopy and metabolomics, the metabolic phenotype and metabolites indicated that the biotic phase significantly changed lipid metabolism as T. caespitum aged. Lipid metabolites were demonstrated as the main factor driving the enrichment of ARGs in T. caespitum. Cuminaldehyde, the antibacterial lipid metabolite that displayed a remarkable increase in the adult phase, was demonstrated to strongly induce ARG abundance. Our findings show that the gut resistome is host developmental stage-dependent and likely modulated by metabolites, offering novel insights into possible steps to reduce ARG dissemination in the soil food chain.


Subject(s)
Anti-Bacterial Agents , Ants , Genes, Bacterial , Humans , Adult , Aged , Anti-Bacterial Agents/pharmacology , Ecosystem , Lipids
12.
New Phytol ; 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38308133

ABSTRACT

Scots pine is the foundation species of diverse forested ecosystems across Eurasia and displays remarkable ecological breadth, occurring in environments ranging from temperate rainforests to arid tundra margins. Such expansive distributions can be favored by various demographic and adaptive processes and the interactions between them. To understand the impact of neutral and selective forces on genetic structure in Scots pine, we conducted range-wide population genetic analyses on 2321 trees from 202 populations using genotyping-by-sequencing, reconstructed the recent demography of the species and examined signals of genetic adaptation. We found a high and uniform genetic diversity across the entire range (global FST 0.048), no increased genetic load in expanding populations and minor impact of the last glacial maximum on historical population sizes. Genetic-environmental associations identified only a handful of single-nucleotide polymorphisms significantly linked to environmental gradients. The results suggest that extensive gene flow is predominantly responsible for the observed genetic patterns in Scots pine. The apparent missing signal of genetic adaptation is likely attributed to the intricate genetic architecture controlling adaptation to multi-dimensional environments. The panmixia metapopulation of Scots pine offers a good study system for further exploration into how genetic adaptation and plasticity evolve under gene flow and changing environment.

13.
Plant Physiol ; 195(1): 652-670, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38412470

ABSTRACT

Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid "84K" (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.


Subject(s)
Alleles , Genome, Plant , Populus , Populus/genetics , Genome, Plant/genetics , Gene Expression Regulation, Plant , Haplotypes/genetics , Hybridization, Genetic , Machine Learning
14.
Int J Biol Sci ; 20(1): 200-217, 2024.
Article in English | MEDLINE | ID: mdl-38164169

ABSTRACT

TGF-ß/Smad3 signaling plays a critical role in type 2 diabetes (T2D) and type 2 diabetic nephropathy (T2DN), but treatment by specifically targeting Smad3 remains unexplored. To develop a new Smad3-targeted therapy for T2D and T2DN, we treated db/db mice at the pre-diabetic or established diabetic stage with a pharmacological Smad3 inhibitor SIS3. The therapeutic effect and mechanisms of anti-Smad3 treatment on T2D and T2DN were investigated. We found that anti-Smad3 treatment on pre-diabetic db/db mice largely attenuated both T2D and T2DN by markedly reducing blood glucose levels, and inhibiting the elevated serum creatinine, microalbuminuria, and renal fibrosis and inflammation. Unexpectedly, although SIS3 treatment on the established diabetic db/db mice inhibited T2DN but did not significantly improve T2D. Mechanistically, we uncovered that inhibition of T2DN in SIS3-treated db/db mice was associated with effectively restoring the balance of TGF-ß/Smad signaling by inhibiting Smad3 while increasing Smad7, thereby suppressing Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation via lncRNA Erbb4-IR and LRN9884-dependent mechanisms. We also revealed that inhibition of islet ß cell injury by preventing the loss of islet Pax 6 could be the mechanism through which the pre-diabetic treatment, rather than the late SIS3 treatment on db/db mice significantly improved the T2D phenotype.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Prediabetic State , Mice , Animals , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/genetics , Diabetes Mellitus, Type 2/genetics , Prediabetic State/complications , Prediabetic State/pathology , Inflammation , Transforming Growth Factor beta/metabolism , Fibrosis , Smad3 Protein/genetics , Smad3 Protein/metabolism , Kidney/pathology
15.
ACS Appl Mater Interfaces ; 16(5): 6533-6547, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38261539

ABSTRACT

Total volatile basic nitrogen (TVB-N) is a vital indicator for assessing seafood freshness and edibility. Rapid on-site detection of volatile basic nitrogen (VBN) is of significant importance for food safety monitoring. In this study, highly luminescent self-assembled copper nanoclusters (Cu NCs@p-MBA), synthesized using p-mercaptobenzoic acid (p-MBA) as the ligand, were utilized for the sensitive detection of VBNs. Under acidic conditions, Cu NCs@p-MBA formed compact and well-organized nanosheets through noncovalent interactions, accompanied by intense orange fluorescence emission (651 nm). The benzene carboxylic acid part of Cu NCs@p-MBA provided the driving force for supramolecular assembly and exhibited a strong affinity for amines, particularly low-molecular-weight amines such as ammonia (NH3) and trimethylamine (TMA). The quantitative determination of NH3 and TMA showed the detection limits as low as 0.33 and 0.81 ppm, respectively. Cu NCs@p-MBA also demonstrated good responsiveness to putrescine and histamine. Through density functional theory (DFT) calculations and molecular dynamics (MD) simulations, the precise atomic structure, assembly structure, luminescent properties, and reaction processes of Cu NCs@p-MBA were studied, revealing the sensing mechanism of Cu NCs@p-MBA for highly sensitive detection of VBNs. Based on the self-assembled Cu NCs@p-MBA nanosheets, portable fluorescent labels were developed for semiquantitative, visual, and real-time monitoring of seafood freshness. Therefore, this study exemplified the high sensitivity of self-assembly induced emission (SAIE)-type Cu NCs@p-MBA for VBNs sensing, offering an efficient solution for on-site monitoring of seafood freshness.


Subject(s)
Copper , Nitrogen , Copper/chemistry , Fluorescent Dyes/chemistry , Histamine , Seafood
16.
Biomed Pharmacother ; 171: 116175, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38266620

ABSTRACT

Bacterial infections are a significant global health concern, particularly in the context of skin infections and chronic wounds, which was further exacerbated by the emerging of antibiotic resistance. Therefore, there are urgent needs to develop alternative antibacterial strategies without inducing significant resistance. Photothermal therapy (PTT) is a promising alternative approach but usually faces limitations such as the need for stable and environmental-friendly PTT agents and ensuring biocompatibility with living tissues, necessitating ongoing research for its clinical advancement. Herein, in this study, with the aim to develop a green synthesized PTT agent for photothermal enhanced antibacterial and wound healing, we proposed a facile one-pot method to prepare epigallocatechin gallate-ferric (EGCG-Fe) complex nanoparticles. The obtained nanoparticles showed improved good size distribution and stability with high reproducibility. More importantly, EGCG-Fe complex nanoparticles have additional photothermal conversion ability which can give photothermal enhanced antibacterial effect on various pathogens, including Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) strains. EGCG-Fe complex nanoparticles also showed powerful biofilm prevention and destruction effects with promoted antibacterial and wound healing on mice model. In conclusion, EGCG-Fe complex nanoparticles can be a robust green material with effective and novel light controllable antibacterial properties for photothermal enhanced antibacterial and wound healing applications.


Subject(s)
Catechin/analogs & derivatives , Escherichia coli , Nanoparticles , Animals , Mice , Reproducibility of Results , Staphylococcus aureus , Iron , Anti-Bacterial Agents , Electrolytes , Wound Healing
17.
Sci Adv ; 10(2): eadk4620, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38198540

ABSTRACT

Collecting energy from the ubiquitous water cycle has emerged as a promising technology for power generation. Here, we have developed a sustainable moisture absorption-evaporation cycling fabric (Mac-fabric). On the basis of the cycling unidirectional moisture conduction in the fabric and charge separation induced by the negative charge channel, sustainable constant voltage power generation can be achieved. A single Mac-fabric can achieve a high power output of 0.144 W/m2 (5.76 × 102 W/m3) at 40% relative humidity (RH) and 20°C. By assembling 500 series and 300 parallel units of Mac-fabrics, a large-scale demo achieves 350 V of series voltage and 33.76 mA of parallel current at 25% RH and 20°C. Thousands of Mac-fabric units are sewn into a tent to directly power commercial electronic products such as mobile phones in outdoor environments. The lightweight (300 g/m2) and soft characteristics of the Mac-fabric make it ideal for large-area integration and energy collection in real circumstances.

18.
Plant Physiol ; 194(2): 787-804, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-37815230

ABSTRACT

Root development influences plant responses to environmental conditions, and well-developed rooting enhances plant survival under abiotic stress. However, the molecular and genetic mechanisms underlying root development and abiotic stress tolerance in plants remain unclear. In this study, we identified the MYB transcription factor-encoding gene IbMYB73 by cDNA-amplified fragment length polymorphism and RNA-seq analyses. IbMYB73 expression was greatly suppressed under abiotic stress in the roots of the salt-tolerant sweet potato (Ipomoea batatas) line ND98, and its promoter activity in roots was significantly reduced by abscisic acid (ABA), NaCl, and mannitol treatments. Overexpression of IbMYB73 significantly inhibited adventitious root growth and abiotic stress tolerance, whereas IbMYB73-RNAi plants displayed the opposite pattern. IbMYB73 influenced the transcription of genes involved in the ABA pathway. Furthermore, IbMYB73 formed homodimers and activated the transcription of ABA-responsive protein IbGER5 by binding to an MYB binding sites I motif in its promoter. IbGER5 overexpression significantly inhibited adventitious root growth and abiotic stress tolerance concomitantly with a reduction in ABA content, while IbGER5-RNAi plants showed the opposite effect. Collectively, our results demonstrated that the IbMYB73-IbGER5 module regulates ABA-dependent adventitious root growth and abiotic stress tolerance in sweet potato, which provides candidate genes for the development of elite crop varieties with well-developed root-mediated abiotic stress tolerance.


Subject(s)
Abscisic Acid , Ipomoea batatas , Abscisic Acid/pharmacology , Abscisic Acid/metabolism , Ipomoea batatas/genetics , Ipomoea batatas/metabolism , Plants, Genetically Modified/metabolism , Amplified Fragment Length Polymorphism Analysis , Stress, Physiological/physiology , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism
19.
Brain ; 147(1): 311-324, 2024 01 04.
Article in English | MEDLINE | ID: mdl-37713627

ABSTRACT

Highly conserved transport protein particle (TRAPP) complexes regulate subcellular trafficking pathways. Accurate protein trafficking has been increasingly recognized to be critically important for normal development, particularly in the nervous system. Variants in most TRAPP complex subunits have been found to lead to neurodevelopmental disorders with diverse but overlapping phenotypes. We expand on limited prior reports on TRAPPC6B with detailed clinical and neuroradiologic assessments, and studies on mechanisms of disease, and new types of variants. We describe 29 additional patients from 18 independent families with biallelic variants in TRAPPC6B. We identified seven homozygous nonsense (n = 12 patients) and eight canonical splice-site variants (n = 17 patients). In addition, we identified one patient with compound heterozygous splice-site/missense variants with a milder phenotype and one patient with homozygous missense variants. Patients displayed non-progressive microcephaly, global developmental delay/intellectual disability, epilepsy and absent expressive language. Movement disorders including stereotypies, spasticity and dystonia were also observed. Brain imaging revealed reductions in cortex, cerebellum and corpus callosum size with frequent white matter hyperintensity. Volumetric measurements indicated globally diminished volume rather than specific regional losses. We identified a reduced rate of trafficking into the Golgi apparatus and Golgi fragmentation in patient-derived fibroblasts that was rescued by wild-type TRAPPC6B. Molecular studies revealed a weakened interaction between mutant TRAPPC6B (c.454C>T, p.Q152*) and its TRAPP binding partner TRAPPC3. Patient-derived fibroblasts from the TRAPPC6B (c.454C>T, p.Q152*) variant displayed reduced levels of TRAPPC6B as well as other TRAPP II complex-specific members (TRAPPC9 and TRAPPC10). Interestingly, the levels of the TRAPPC6B homologue TRAPPC6A were found to be elevated. Moreover, co-immunoprecipitation experiments showed that TRAPPC6A co-precipitates equally with TRAPP II and TRAPP III, while TRAPPC6B co-precipitates significantly more with TRAPP II, suggesting enrichment of the protein in the TRAPP II complex. This implies that variants in TRAPPC6B may preferentially affect TRAPP II functions compared to TRAPP III functions. Finally, we assessed phenotypes in a Drosophila TRAPPC6B-deficiency model. Neuronal TRAPPC6B knockdown impaired locomotion and led to wing posture defects, supporting a role for TRAPPC6B in neuromotor function. Our findings confirm the association of damaging biallelic TRAPPC6B variants with microcephaly, intellectual disability, language impairments, and epilepsy. A subset of patients also exhibited dystonia and/or spasticity with impaired ambulation. These features overlap with disorders arising from pathogenic variants in other TRAPP subunits, particularly components of the TRAPP II complex. These findings suggest that TRAPPC6B is essential for brain development and function, and TRAPP II complex activity may be particularly relevant for mediating this function.


Subject(s)
Dystonia , Epilepsy , Intellectual Disability , Microcephaly , Neurodevelopmental Disorders , Animals , Humans , Microcephaly/genetics , Intellectual Disability/genetics , Vesicular Transport Proteins/genetics , Neurodevelopmental Disorders/genetics , Epilepsy/genetics
20.
Water Res ; 249: 121008, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38096729

ABSTRACT

Phytoremediation, which is commonly carried out through hydroponics and substrate-based strategies, is essential for the effectiveness of nature-based engineered solutions aimed at addressing excess nitrogen in aquatic ecosystems. However, the performance and mechanisms of plants involving nitrogen removal between different strategies need to be deeply understood. Here, this study employed in-situ cultivation coupled with static nitrogen tracing experiments to elucidate the influence of both strategies on plant traits associated with nitrogen removal. The results indicated that removal efficiencies in plants with substrate-based strategies for ammonium nitrogen and nitrate nitrogen were 30.51-71.11 % and 16.82-99.95 %, respectively, which were significantly higher than those with hydroponics strategies (25.98-58.18 % and 7.29-79.19 %, respectively). Similarly, the plant nitrogen uptake rates in the substrate-based strategy also generally showed higher levels compared to hydroponics strategies (P < 0.05). Meanwhile, the microorganisms-mediated nitrous oxide emission rates in the substrate-based strategy during summer (unamended: 0.00-0.58 µg/g/d; potential: 3.35-7.65 µg/g/d) were obviously lower than those in the hydroponics strategy (unamended: 2.23-11.70 µg/g/d; potential: 9.72-43.09 µg/g/d) (P < 0.05). Notably, analysis of similarity tests indicated that the influences of strategy on the above parameters generally surpass the effects attributable to interspecies plant differences, particularly during summer (R > 0, P < 0.05). Based on statistical and metagenomic analyses, this study revealed that these differences were driven by the stabilizing influence of substrate-based strategy on plant roots and enhancing synergistic interplay among biochemical factors within plant-root systems. Even so, phytoremediation strategies did not significantly alter the characteristics of plants with regards to their tendency towards ammonium nitrogen uptake (up to 87.68 %) and dissimilatory nitrate reduction to ammonium as primary biological pathway for nitrogen transformation which accounted for 53.66-96.47 % nitrate removal. In summary, this study suggested that the substrate-based strategy should be a more effective strategy for enhancing the nitrogen removal ability of plants in subtropical river restoration practices.


Subject(s)
Ammonium Compounds , Nitrates , Ecosystem , Biodegradation, Environmental , Rivers , Nitrogen/metabolism , Denitrification
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