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1.
FASEB J ; 38(13): e23737, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38953724

ABSTRACT

Meningiomas are the most common primary intracranial tumors and account for nearly 30% of all nervous system tumors. Approximately half of meningioma patients exhibit neurofibromin 2 (NF2) gene inactivation. Here, NF2 was shown to interact with the endoplasmic reticulum (ER) calcium (Ca2+) channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in IOMM-Lee, a high-grade malignant meningioma cell line, and the F1 subdomain of NF2 plays a critical role in this interaction. Functional assays indicated that NF2 promotes the phosphorylation of IP3R (Ser 1756) and IP3R-mediated endoplasmic reticulum (ER) Ca2+ release by binding to IP3R1, which results in Ca2+-dependent apoptosis. Knockout of NF2 decreased Ca2+ release and promoted resistance to apoptosis, which was rescued by wild-type NF2 overexpression but not by F1 subdomain deletion truncation overexpression. The effects of NF2 defects on the development of tumors were further studied in mouse models. The decreased expression level of NF2 caused by NF2 gene knockout or mutation affects the activity of the IP3R channel, which reduces Ca2+-dependent apoptosis, thereby promoting the development of tumors. We elucidated the interaction patterns of NF2 and IP3R1, revealed the molecular mechanism through which NF2 regulates IP3R1-mediated Ca2+ release, and elucidated the new pathogenic mechanism of meningioma-related NF2 variants. Our study broadens the current understanding of the biological function of NF2 and provides ideas for drug screening of NF2-associated meningioma.


Subject(s)
Apoptosis , Calcium Signaling , Calcium , Inositol 1,4,5-Trisphosphate Receptors , Meningeal Neoplasms , Meningioma , Inositol 1,4,5-Trisphosphate Receptors/metabolism , Inositol 1,4,5-Trisphosphate Receptors/genetics , Meningioma/metabolism , Meningioma/pathology , Meningioma/genetics , Humans , Animals , Mice , Meningeal Neoplasms/metabolism , Meningeal Neoplasms/pathology , Meningeal Neoplasms/genetics , Calcium/metabolism , Cell Line, Tumor , Endoplasmic Reticulum/metabolism , Male , Neurofibromin 2
2.
World J Gastroenterol ; 30(21): 2751-2762, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38899331

ABSTRACT

Inflammatory bowel disease (IBD) is believed to be caused by various factors, including abnormalities in disease susceptibility genes, environmental factors, immune factors, and intestinal bacteria. Proton pump inhibitors (PPIs) are the primary drugs used to treat acid-related diseases. They are also commonly prescribed to patients with IBD. Recent studies have suggested a potential association between the use of certain medications, such as PPIs, and the occurrence and progression of IBD. In this review, we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms. Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.


Subject(s)
Inflammatory Bowel Diseases , Proton Pump Inhibitors , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/immunology , Disease Progression , Gastrointestinal Microbiome/drug effects , Gastroesophageal Reflux/drug therapy
3.
Clin Interv Aging ; 19: 681-693, 2024.
Article in English | MEDLINE | ID: mdl-38706635

ABSTRACT

Aging and aging-related diseases present a global public health problem. Therefore, the development of efficient anti-aging drugs has become an important area of research. Traditional Chinese medicine is an important complementary and alternative branch of aging-related diseases therapy. Recently, a growing number of studies have revealed that traditional Chinese medicine has a certain delaying effect on the progression of aging and aging-related diseases. Here, we review the progress in research into using traditional Chinese medicine for aging and aging-related diseases (including neurodegenerative diseases, cardiovascular diseases, diabetes, and cancer). Furthermore, we summarize the potential mechanisms of action of traditional Chinese medicine and provide references for further studies on aging and aging-related diseases.


Subject(s)
Aging , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Neoplasms , Neurodegenerative Diseases , Humans , Aging/drug effects , Medicine, Chinese Traditional/methods , Neurodegenerative Diseases/drug therapy , Neoplasms/drug therapy , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Diabetes Mellitus/drug therapy
4.
Biomed Environ Sci ; 37(4): 354-366, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38727158

ABSTRACT

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.


Subject(s)
Inflammation , Mercury , PTEN Phosphohydrolase , Humans , Down-Regulation , HEK293 Cells , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Interleukin-6/blood , Mercury/toxicity , Occupational Exposure/adverse effects , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Signal Transduction/drug effects
5.
Psychol Res Behav Manag ; 17: 1515-1531, 2024.
Article in English | MEDLINE | ID: mdl-38601263

ABSTRACT

Purpose: Recent research has focused on the impact of communication networks on the performance of construction project teams, attempting empirical exploration from various social network analysis perspectives. However, there is still a significant gap in understanding the variations in performance and the mechanisms for teams using different communication networks. Drawing from organizational learning theory and social network theory, this study, based on the Input-Mediator-Output (IMO) model, explores the effects of the interaction between centralization and tie strength in communication networks on team performance, as well as the mediating mechanisms of knowledge sharing behavior and team resilience performance in engineering project teams. Methods: Drawing on classic group communication experiment, we design an online communication and collaboration platform to simulate the execution of a construction engineering project. Finally, data was collected through the communication experiment with 720 participants, and hypotheses were tested using ANOVA and PROCESS. Results: The results indicate that under conditions of weak tie strength, centralized communication networks yield higher performance. Conversely, under conditions of strong tie strength, decentralized communication networks demonstrate superior performance. Furthermore, this study also verifies the mediating role of knowledge sharing behavior and team resilience performance when tie strength is strong. Conclusion: This study focuses on engineering project team, exploring the evolutionary development of knowledge sharing behavior and team resilience performance from the perspective of the interaction of communication network structural characteristics, as well as the paths to enhancing team performance. Our research results highlight the interactive effects of structural indicators and relational indicators of communication networks, revealing the mechanism by which the structure of communication networks impacts team performance. Additionally, from the perspectives of forming and timely adjusting team communication models, and motivating and supporting employee communication behavior, our study provides practical insights for project managers and relevant administrators.

6.
Adv Mater ; : e2312093, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38683953

ABSTRACT

Carbon dioxide (CO2), a member of greenhouse gases, contributes significantly to maintaining a tolerable environment for all living species. However, with the development of modern society and the utilization of fossil fuels, the concentration of atmospheric CO2 has increased to 400 ppm, resulting in a serious greenhouse effect. Thus, converting CO2 into valuable chemicals is highly desired, especially with renewable solar energy, which shows great potential with the manner of photothermal catalysis. In this review, recent advancements in photothermal CO2 conversion are discussed, including the design of catalysts, analysis of mechanisms, engineering of reactors, and the corresponding techno-economic analysis. A guideline for future investigation and the anthropogenic carbon cycle are provided.

7.
Matern Child Nutr ; 20(3): e13653, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38624183

ABSTRACT

Maternal anaemia is a major public health problem. Developing maternal anaemia prevention and control policies is an important prerequisite for carrying out evidence-based interventions. This article reviews maternal anaemia prevention and control policies in China, identifies gaps, and provides references for other countries. We examined policies concerning maternal nutrition and other related literature in China, identified through key databases and government websites, and conducted a narrative review of the relevant documentations guided by the Smith Policy-Implementing-Process framework. A total of 65 articles and documents were identified for analysis. We found that Chinese government has committed to reducing maternal anaemia at the policy level, with established objectives and a clear time frame. However, most of policies were not accompanied by operational guidelines, standardized interventions, and vigorous monitoring and evaluation mechanisms, and 85% of the policies don't have quantifiable objectives on anaemia. Maternal anaemia prevention and control services offered in clinical settings were primarily nutrition education and anaemia screening. Population-based interventions such as iron fortification have yet to be scaled up. Furthermore, medical insurance schemes in some regions do not cover anaemia prevention and treatment, and in other regions that offer coverage, the reimbursement rate is low. The number and capacity of health professionals is also limited. Policy changes should focus on the integration of evidence-based interventions into routine antenatal care services and public health service packages, standardization of dosages and provision of iron supplementation, streamline of reimbursement for outpatient expenses, and capacity building of health professionals.


Subject(s)
Anemia , Health Policy , Humans , Female , China , Pregnancy , Anemia/prevention & control , Health Policy/legislation & jurisprudence , Prenatal Care , Maternal Nutritional Physiological Phenomena , Nutrition Policy/legislation & jurisprudence , Anemia, Iron-Deficiency/prevention & control , Pregnancy Complications, Hematologic/prevention & control
8.
Eur J Radiol ; 175: 111479, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663124

ABSTRACT

PURPOSE: To construct and validate CT radiomics model based on the peritumoral adipose region of gastric adenocarcinoma to preoperatively predict lymph node metastasis (LNM). METHODS AND METHODS: 293 consecutive gastric adenocarcinoma patients receiving radical gastrectomy with lymph node dissection in two medical institutions were stratified into a development set (from Institution A, n = 237), and an external validation set (from Institution B, n = 56). Volume of interest of peritumoral adipose region was segmented on preoperative portal-phase CT images. The least absolute shrinkage and selection operator method and stepwise logistic regression were used to select features and build radiomics models. Manual classification was performed according to routine CT characteristics. A classifier incorporating the radiomics score and CT characteristics was developed for predicting LNM. Area under the receiver operating characteristic curve (AUC) was used to show discrimination between tumors with and without LNM, and the calibration curves and Brier score were used to evaluate the predictive accuracy. Violin plots were used to show the distribution of radiomics score. RESULTS: AUC values of radiomics model to predict LNM were 0.938, 0.905, and 0.872 in the training, internal test, and external validation sets, respectively, higher than that of manual classification (0.674, all P values < 0.01). The radiomics score of the positive LNM group were higher than that of the negative group in all sets (both P-values < 0.001). The classifier showed no improved predictive power compared with the radiomics signature alone with AUC values of 0.916 and 0.872 in the development and external validation sets, respectively. Multivariate analysis showed that radiomics score was an independent predictor. CONCLUSIONS: Radiomics model based on peritumoral adipose region could be a useful approach for preoperative LNM prediction in gastric adenocarcinoma.


Subject(s)
Adenocarcinoma , Adipose Tissue , Lymphatic Metastasis , Stomach Neoplasms , Tomography, X-Ray Computed , Humans , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Male , Female , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Tomography, X-Ray Computed/methods , Middle Aged , Lymphatic Metastasis/diagnostic imaging , Aged , Adipose Tissue/diagnostic imaging , Adipose Tissue/pathology , Predictive Value of Tests , Adult , Gastrectomy , Retrospective Studies , Reproducibility of Results , Lymph Node Excision , Radiomics
10.
Front Microbiol ; 15: 1346955, 2024.
Article in English | MEDLINE | ID: mdl-38435694

ABSTRACT

Diarrheal acquired immune deficiency syndrome (AIDS) seriously affects the quality of life of patients. In this study, we analyzed the differences in the intestinal microbiota among healthy individuals, AIDS patients without diarrhea and AIDS patients with diarrhea through high-throughput sequencing. The microbial diversity in the intestines of patients in the AIDS diarrhea group was significantly increased, and after treatment with Xielikang, the intestinal microbial diversity returned to the baseline level. At the phylum level, compared those in to the healthy (ZC) and AIDS non diarrhea (FN) groups, the relative abundances of Bacteroidetes and Verrucomirobia in the AIDS diarrhea (FA) group before treatment were significantly increased, while the relative abundance of Firmicutes was significantly decreased. Similarly, compared with those in the FA group, the relative abundances of Bacteroidea and Firmicutes in the AIDS diarrhea (FB) group after treatment were significantly increased, while the relative abundance of Firmicutes was significantly decreased after treatment. Additionally, there was no significant difference between the ZC and FN groups. At the genus level, compared with those in the ZC group, the relative abundance of Prevotella and Escherichia_Shigella in the FA group was significantly increased, while the relative abundances of Megamonas and Bifidobacterium was significantly decreased compared to that in the ZC group. After treatment with Xielikang, the relative abundance of Prevotella and Escherichia_Shigella in the FB group were significantly decreased, while the relative abundances of Megamonas and Bifidobacteria were significantly increased than those in the FA group; moreover, there was no significant difference between the ZC and FN groups. The functional prediction results showed that the ketodeoxyoctonate (Kdo) transfer to lipid IVA III and the superpathway of N-acetylglucosamine pathways in the AIDS diarrhea group were significantly altered. The correlation analysis results showed that Dorea was positively correlated with inflammatory factors, while Streptococcus and Lactobacillus were negatively correlated with inflammatory factors. The composition and function of the intestinal microbiota changed significantly in AIDS diarrhea patients, which affected the immune function of the host. The Xielikang capsule modulated the composition of the intestinal microbiota in AIDS diarrhea patients and thus improved immune function and reduced diarrheal symptoms.

11.
J Agric Food Chem ; 72(12): 6236-6249, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38484389

ABSTRACT

Hypercholesterolemia poses a significant cardiovascular risk, particularly in postmenopausal women. The anti-hypercholesterolemic properties of Lactiplantibacillus plantarum ATCC8014 (LP) are well recognized; however, its improving symptoms on postmenopausal hypercholesterolemia and the possible mechanisms have yet to be elucidated. Here, we utilized female ApoE-deficient (ApoE-/-) mice undergoing bilateral ovariectomy, fed a high-fat diet, and administered 109 colony-forming units (CFU) of LP for 13 consecutive weeks. LP intervention reduces total cholesterol (TC) and triglyceride (TG) accumulation in the serum and liver and accelerates their fecal excretion, which is mainly accomplished by increasing the excretion of fecal secondary bile acids (BAs), thereby facilitating cholesterol conversion. Correlation analysis revealed that lithocholic acid (LCA) is an important regulator of postmenopausal lipid abnormalities. LP can reduce LCA accumulation in the liver and serum while enhancing its fecal excretion, accomplished by elevating the relative abundances of Allobaculum and Olsenella in the ileum. Our findings demonstrate that postmenopausal lipid dysfunction is accompanied by abnormalities in BA metabolism and dysbiosis of the intestinal microbiota. LP holds therapeutic potential for postmenopausal hypercholesterolemia. Its effectiveness in ameliorating lipid dysregulation is primarily achieved through reshaping the diversity and abundance of the intestinal microbiota to correct BA abnormalities.


Subject(s)
Gastrointestinal Microbiome , Hypercholesterolemia , Lactobacillus plantarum , Humans , Female , Mice , Animals , Hypercholesterolemia/metabolism , Bile Acids and Salts/metabolism , Postmenopause , Cholesterol/metabolism , Lactobacillus plantarum/metabolism , Liver/metabolism , Apolipoproteins E/metabolism , Mice, Inbred C57BL , Diet, High-Fat
12.
Exp Ther Med ; 27(3): 121, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38361513

ABSTRACT

It has been reported that the force of orthodontic correction triggers periodontal tissue remodeling by affecting angiogenesis. However, the manifestation of the vascular response to orthodontic tooth movement in the setting of chronic fluorosis is unclear. The aim of the present study was to preliminarily explore the effect of orthodontic treatment on the angiogenesis of gingival tissue in rats with chronic fluorosis by monitoring changes in the expression of vascular endothelial growth factor (VEGF), phosphatidylinositol-3 kinase (PI3K), AKT (or protein kinase B) and endothelial nitric oxide synthase (eNOS) in the gingival tissue. A total of 60 rats were randomly divided equally into the orthodontic group (O group; n=30) and fluorosis orthodontic group (FO group; n=30). Each of these groups was divided into 0-, 3-, 7-, 14- and 21-day groups (n=6/group). Fluorosis and orthodontic tooth movement models were established, and rats in each group were sacrificed for tissue sampling at the corresponding time points. Tissue morphology was observed via hematoxylin and eosin (H&E) staining. The protein and mRNA expression levels of VEGF, PI3K, AKT and eNOS in gingival tissue were detected by western blotting and reverse transcription-quantitative polymerase chain reaction, respectively. The H&E staining images showed that the FO group had smaller blood vessels and reduced vascular proliferation compared with the O group. Furthermore, the mRNA and protein expression levels of VEGF, PI3K, AKT and eNOS were reduced in the gingiva of rats in the FO group compared with the O group, and certain reductions were significant during the delayed tooth movement period. In addition, with the extension of the application of orthodontic stress, the mRNA and protein expression levels of VEGF, PI3K, AKT and eNOS in the gingiva of the O and FO groups showed a trend of increasing at first and subsequently decreasing, which corresponds with the tooth movement cycle. In conclusion, chronic fluorosis may inhibit the angiogenesis and the expression of the VEGF/PI3K/AKT/eNOS pathway in gingival tissue of orthodontic tooth movement.

13.
AIDS Res Ther ; 21(1): 10, 2024 02 13.
Article in English | MEDLINE | ID: mdl-38350942

ABSTRACT

Acquired Immune Deficiency Syndrome (AIDS) is a highly dangerous infectious disease caused by the Human Immunodeficiency Virus (HIV), a virus that attacks the human immune system. To explore the correlation between intestinal fungal community and immune function (Immune cells and inflammatory factors) in people living with HIV/AIDS (PLWHA). The feces and blood samples were collected from two groups of subjects: PLWHA and healthy controls. High-throughput sequencing of the internal transcribed spacer 1, flow cytometry, and ELISA were performed to analyze the differences and correlations between fungal microbiota, cellular immune status and serum inflammatory factors in the two groups. There were significant differences in the composition of fungal microbiota between the two groups. The relative abundance of Candida, Bjerkandera, and Xeromyces in PLWHA was significantly higher than that of healthy volunteers (P < 0.01), while the relative abundance of Mycospaerella, Xeroxysium, Penicillium, and Glomerella in PLWHA was significantly lower than that of healthy volunteers. The correlation analysis results show that Mycospaerella and Xeromyces are significantly positively correlated with CD4+/CD8+ T cells and the anti-inflammatory cytokine IL-4. On the other hand, Candida was positively correlated with pro-inflammatory factors negatively correlated with CD4+/CD8+ T cells and the anti-inflammatory cytokine IL-4, while it is positively correlated with pro-inflammatory cytokines. The significant increase in the relative abundance of Candida may be one of the important causes of intestinal damage in PLWHA. The results of this study contribute to the understanding of the relationship between fungal microbiota structure and immune function in the gut ecology of PLWHA.


Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Mycobiome , Humans , CD8-Positive T-Lymphocytes , Interleukin-4 , Cytokines , Anti-Inflammatory Agents
14.
Adv Mater ; 36(21): e2312942, 2024 May.
Article in English | MEDLINE | ID: mdl-38354694

ABSTRACT

High entropy alloys and metallic glasses, as two typical metastable nanomaterials, have attracted tremendous interest in energy conversion catalysis due to their high reactivity in nonequilibrium states. Herein, a novel nanomaterial, layered high entropy metallic glass (HEMG), in a higher energy state than low-entropy alloys and its crystalline counterpart due to both the disordered elemental and structural arrangements, is synthesized. Specifically, the MnNiZrRuCe HEMG exhibits highly enhanced photothermal catalytic activity and long-term stability. An unprecedented CO2 methanation rate of 489 mmol g-1 h-1 at 330 °C is achieved, which is, to the authors' knowledge, the highest photothermal CO2 methanation rate in flow reactors. The remarkable activity originates from the abundant free volume and high internal energy state of HEMG, which lead to the extraordinary heterolytic H2 dissociation capacity. The high-entropy effect also ensures the excellent stability of HEMG for up to 450 h. This work not only provides a new perspective on the catalytic mechanism of HEMG, but also sheds light on the great catalytic potential in future carbon-negative industry.

15.
Angew Chem Int Ed Engl ; 63(12): e202315777, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38233351

ABSTRACT

Electrochemical CO2 reduction can convert CO2 to value-added chemicals, but its selectivity toward C3+ products are very limited. One possible solution is to run the reactions in hybrid processes by coupling electrocatalysis with other catalytic routes. In this contribution, we report the cascade electrocatalytic and thermocatalytic reduction of CO2 to propionaldehyde. Using Cu(OH)2 nanowires as the precatalyst, CO2 /H2 O is reduced to concentrated C2 H4 , CO, and H2 gases in a zero-gap membrane electrode assembly (MEA) reactor. The thermochemical hydroformylation reaction is separately investigated with a series of rhodium-phosphine complexes. The best candidate is identified to be the one with the 1,4-bis(diphenylphosphino)butane diphosphine ligand, which exhibits a propionaldehyde turnover number of 1148 under a mild temperature and close-to-atmospheric pressure. By coupling and optimizing the upstream CO2 electroreduction and downstream hydroformylation reaction, we achieve a propionaldehyde selectivity of ~38 % and a total C3 oxygenate selectivity of 44 % based on reduced CO2 . These values represent a more than seven times improvement over the best prior electrochemical system alone or over two times improvement over other hybrid systems.

16.
Environ Sci Pollut Res Int ; 31(7): 11010-11025, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38217810

ABSTRACT

As the main supply source of lakes, the water quality of the rivers entering the lakes directly determines the water safety and sustainable development of the lakes. Human activities are the direct cause of changes in the water quality of rivers entering lakes, and land use intensity is the direct manifestation of human activities on the land surface. Although significant progress has been made in studying the relationship between land use changes and water quality in lakes, there is still a lack of research on exploring the relationship between land use intensity and water quality at multiple scales, especially in comparative studies of different pollution source areas. To address this problem, this study used Pearson's correlation analysis and land use intensity index method to explore the response relationship between river water quality and land use intensity at different spatial and temporal scales and different pollution source areas using three lakes in central Yunnan as examples. The results showed that land use intensity was generally positively correlated with water quality, but the response relationship between land use intensity and different water quality indicators was significantly different at different scales and for different pollution source areas. Compared to non-urban areas, the impact of land use intensity on water quality is more significant in urban areas. Compared to the rainy season, the correlation between CODNa, TP, and NH3-N values and land use intensity is stronger during the dry season, while the correlation between COD, TN, and land use intensity is weaker during the dry season. When viewed at different scales, different water quality indicators have different scale effects, but overall, the larger the scale, the stronger the correlation. Therefore, in the work of lake water environmental governance, it is necessary to consider comprehensively from multiple scales and perspectives and adopt measures that are more suitable for regional water pollution prevention and control.


Subject(s)
Water Pollutants, Chemical , Water Quality , Humans , Lakes , Rivers , Environmental Monitoring/methods , Conservation of Natural Resources , Water Pollutants, Chemical/analysis , Nitrogen/analysis , Phosphorus/analysis , China , Environmental Policy
17.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 167024, 2024 03.
Article in English | MEDLINE | ID: mdl-38242180

ABSTRACT

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).


Subject(s)
Deferoxamine , Ototoxicity , Humans , tert-Butylhydroperoxide/toxicity , tert-Butylhydroperoxide/metabolism , Deferoxamine/pharmacology , Ototoxicity/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Hair Cells, Auditory/metabolism , Iron/metabolism
18.
Nat Prod Bioprospect ; 14(1): 7, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38200389

ABSTRACT

Metagenomics has opened new avenues for exploring the genetic potential of uncultured microorganisms, which may serve as promising sources of enzymes and natural products for industrial applications. Identifying enzymes with improved catalytic properties from the vast amount of available metagenomic data poses a significant challenge that demands the development of novel computational and functional screening tools. The catalytic properties of all enzymes are primarily dictated by their structures, which are predominantly determined by their amino acid sequences. However, this aspect has not been fully considered in the enzyme bioprospecting processes. With the accumulating number of available enzyme sequences and the increasing demand for discovering novel biocatalysts, structural and functional modeling can be employed to identify potential enzymes with novel catalytic properties. Recent efforts to discover new polysaccharide-degrading enzymes from rumen metagenome data using homology-based searches and machine learning-based models have shown significant promise. Here, we will explore various computational approaches that can be employed to screen and shortlist metagenome-derived enzymes as potential biocatalyst candidates, in conjunction with the wet lab analytical methods traditionally used for enzyme characterization.

19.
Hear Res ; 441: 108919, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38043402

ABSTRACT

Auditory neuropathy spectrum disorder (ANSD) is a hearing impairment involving disruptions to inner hair cells (IHCs), ribbon synapses, spiral ganglion neurons (SGNs), and/or the auditory nerve itself. The outcomes of cochlear implants (CI) for ANSD are variable and dependent on the location of lesion sites. Discovering a potential therapeutic agent for ANSD remains an urgent requirement. Here, 293T stable transfection cell lines and patient induced pluripotent stem cells (iPSCs)-derived auditory neurons carrying the apoptosis inducing factor (AIF) p.R422Q variant were used to pursue a therapeutic regent for ANSD. Nicotinamide adenine dinucleotide (NADH) is a main electron donor in the electron transport chain (ETC). In 293T stable transfection cells with the p.R422Q variant, NADH treatment improved AIF dimerization, rescued mitochondrial dysfunctions, and decreased cell apoptosis. The effects of NADH were further confirmed in patient iPSCs-derived neurons. The relative level of AIF dimers was increased to 150.7 % (P = 0.026) from 59.2 % in patient-neurons upon NADH treatment. Such increased AIF dimerization promoted the mitochondrial import of coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4), which further restored mitochondrial functions. Similarly, the content of mitochondrial calcium (mCa2+) was downregulated from 136.7 % to 102.3 % (P = 0.0024) in patient-neurons upon NADH treatment. Such decreased mCa2+ levels inhibited calpain activity, ultimately reducing the percentage of apoptotic cells from 30.5 % to 21.1 % (P = 0.021). We also compared the therapeutic effects of gene correction and NADH treatment on hereditary ANSD. NADH treatment had comparable restorative effects on functions of ANSD patient-specific cells to that of gene correction. Our findings offer evidence of the molecular mechanisms of ANSD and introduce NADH as a potential therapeutic agent for ANSD therapy.


Subject(s)
Apoptosis Inducing Factor , Apoptosis , Hearing Loss, Central , NAD , Sensory Receptor Cells , Hearing Loss, Central/genetics , Hearing Loss, Central/metabolism , Hearing Loss, Central/physiopathology , Apoptosis/drug effects , NAD/pharmacology , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Sensory Receptor Cells/drug effects , Sensory Receptor Cells/metabolism , Dimerization , Mitochondria/drug effects , HEK293 Cells , Mitochondrial Precursor Protein Import Complex Proteins/metabolism , Calcium/metabolism , Reactive Oxygen Species/metabolism , Calpain/metabolism , Enzyme Activation/drug effects , Genotype , Humans , Apoptosis Inducing Factor/genetics , Apoptosis Inducing Factor/metabolism
20.
Small ; 20(10): e2306713, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37919863

ABSTRACT

Luminescent metal clusters have attracted great interest in current research; however, the design synthesis of Al clusters with color-tunable luminescence remains challenging. Herein, an [Al8 (OH)8 (NA)16 ] (Al8 , HNA = nicotinic acid) molecular cluster with dual luminescence properties of fluorescence and room-temperature phosphorescence (RTP) is synthesized by choosing HNA ligand as phosphor. Its prompt photoluminescence (PL) spectrum exhibits approximately white light emission at room temperature. Considering that halogen atoms can be used to regulate the RTP property by balancing the singlet and triplet excitons, different CdX2 (X- = Cl- , Br- , I- ) are introduced into the reactive system of the Al8 cluster, and three new Al8 cluster-based metal-organic frameworks, {[Al8 Cd3 Cl5 (OH)8 (NA)17 H2 O]·2HNA}n (CdCl2 -Al8 ), {[Al8 Cd4 Br7 (OH)8 (NA)16 CH3 CN]·NA·HNA}n (CdBr2 -Al8 ) and {[Al8 Cd8 I16 (OH)8 (NA)16 ]}n (CdI2 -Al8 ) are successfully obtained. They realize the color tunability from blue to yellow at room temperature. The origination of fluorescence and phosphorescence has also been illustrated by structure-property analysis and theoretical calculation. This work provides new insights into the design of multicolor luminescent metal cluster-based materials and develops advanced photo-functional materials for multicolor display, anti-counterfeiting, and encryption applications.

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