Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 243
Filter
1.
Cancer Cell ; 42(8): 1434-1449.e5, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39137728

ABSTRACT

Hypothyroidism is commonly detected in patients with medulloblastoma (MB). However, whether thyroid hormone (TH) contributes to MB pathogenicity remains undetermined. Here, we find that TH plays a critical role in promoting tumor cell differentiation. Reduction in TH levels frees the TH receptor, TRα1, to bind to EZH2 and repress expression of NeuroD1, a transcription factor that drives tumor cell differentiation. Increased TH reverses EZH2-mediated repression of NeuroD1 by abrogating the binding of EZH2 and TRα1, thereby stimulating tumor cell differentiation and reducing MB growth. Importantly, TH-induced differentiation of tumor cells is not restricted by the molecular subgroup of MB, suggesting that TH can be used to broadly treat MB subgroups. These findings establish an unprecedented association between TH signaling and MB pathogenicity, providing solid evidence for TH as a promising modality for MB treatment.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Cell Differentiation , Enhancer of Zeste Homolog 2 Protein , Medulloblastoma , Thyroid Hormones , Medulloblastoma/pathology , Medulloblastoma/metabolism , Medulloblastoma/genetics , Humans , Cell Differentiation/drug effects , Animals , Enhancer of Zeste Homolog 2 Protein/metabolism , Enhancer of Zeste Homolog 2 Protein/genetics , Mice , Thyroid Hormones/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Cerebellar Neoplasms/pathology , Cerebellar Neoplasms/metabolism , Cerebellar Neoplasms/genetics , Cerebellar Neoplasms/drug therapy , Cell Line, Tumor , Disease Progression , Gene Expression Regulation, Neoplastic/drug effects , Thyroid Hormone Receptors alpha/metabolism , Thyroid Hormone Receptors alpha/genetics , Signal Transduction/drug effects
2.
Syst Biol Reprod Med ; 70(1): 249-260, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39167124

ABSTRACT

Despite the significant morphological changes that occur in the seminal vesicles with aging, the transcriptomic characteristics remain largely unexplored. To address this, we performed bulk RNA sequencing on seminal vesicle samples from mice aged 3, 13, and 21 months to uncover transcriptomic alterations. Our findings reveal that aged seminal vesicles display cystic dilatation, epithelial hypoplasia, disordered muscle layers, fibrosis, and reduced proliferation capability. A comparison between 3-month-old and 21-month-old mice indicated that leukocyte-mediated immunity and leukocyte migration were the most significantly upregulated biological processes among differentially expressed genes (DEGs). Notably, several DEGs associated with "leukocyte migration," such as Vcam1, Cxcl13, and Ccl8, exhibited an increasing trend in transcriptomic and protein expression at three different time points in the seminal vesicles of mice. Additionally, we identified multiple aging-associated DEGs, including P21 and Tnfrsf1b. Two genes (Cd209f and Ccl8) were consistently upregulated across all six regions of the male reproductive glands (testis, epididymis, and seminal vesicle) in the comparison of bulk RNA datasets from 3-month-old and 21-month-old mice. These analyses highlight an enhanced state of immune and inflammatory response in aged seminal vesicles. This study represents the first exploration of the overall transcriptome landscape of seminal vesicles in a murine model of natural aging, offering new insights into the mechanisms underlying aging-related seminal vesicle dysfunction.


Subject(s)
Aging , Gene Expression Profiling , Seminal Vesicles , Transcriptome , Animals , Male , Seminal Vesicles/metabolism , Aging/genetics , Mice , Mice, Inbred C57BL
3.
Crit Care ; 28(1): 225, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978111

ABSTRACT

BACKGROUND: The precise identification of the underlying causes of infectious diseases, such as severe pneumonia, is essential, and the development of next-generation sequencing (NGS) has enhanced the effectiveness of pathogen detection. However, there is limited information on the systematic assessment of the clinical use of targeted next-generation sequencing (tNGS) in cases of severe pneumonia. METHODS: A retrospective analysis was conducted on 130 patients with severe pneumonia treated in the ICU from June 2022 to June 2023. The consistency of the results of tNGS, metagenomics next-generation sequencing (mNGS), and culture with the clinical diagnosis was evaluated. Additionally, the results for pathogens detected by tNGS were compared with those of culture, mNGS, and quantitative reverse transcription PCR (RT-qPCR). To evaluate the efficacy of monitoring severe pneumonia, five patients with complicated infections were selected for tNGS microbiological surveillance. The tNGS and culture drug sensitisation results were then compared. RESULTS: The tNGS results for the analysis of the 130 patients showed a concordance rate of over 70% with clinical diagnostic results. The detection of pathogenic microorganisms using tNGS was in agreement with the results of culture, mNGS, and RT-qPCR. Furthermore, the tNGS results for pathogens in the five patients monitored for complicated infections of severe pneumonia were consistent with the culture and imaging test results during treatment. The tNGS drug resistance results were in line with the drug sensitivity results in approximately 65% of the cases. CONCLUSIONS: The application of tNGS highlights its promise and significance in assessing the effectiveness of clinical interventions and providing guidance for anti-infection therapies for severe pneumonia.


Subject(s)
High-Throughput Nucleotide Sequencing , Pneumonia , Humans , Retrospective Studies , High-Throughput Nucleotide Sequencing/methods , Pneumonia/diagnosis , Pneumonia/drug therapy , Pneumonia/microbiology , Male , Female , Middle Aged , Aged , Intensive Care Units/organization & administration , Intensive Care Units/statistics & numerical data
4.
J Environ Manage ; 366: 121761, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38991332

ABSTRACT

Zero-valent iron (Fe0) usually suffers from organic acid complexation and ferrochrome layer passivation in Cr(VI) removal from bioleached wastewater of Cr slag. In this work, a synergetic system combined Fe0 and mixed hetero/autotrophic bacteria was established to reduce and stabilize Cr(VI) from bioleached wastewater. Due to bacterial consumption of organic acid and hydrogen, severe iron corrosion and structured-Fe(II) mineral generation (e.g., magnetite and green rust) occurred on biotic Fe0 surface in terms of solid-phase characterization, which was crucial for Cr(VI) adsorption and reduction. Therefore, compared with the abiotic Fe0 system, this integrated system exhibited a 6.1-fold increase in Cr(VI) removal, with heterotrophic reduction contributing 3.4-fold and abiotic part promoted by hydrogen-autotrophic bacteria enhancing 2.7-fold. After reaction, the Cr valence distribution and X-ray photoelectron spectroscopy indicated that most Cr(VI) was converted into immobilized products such as FexCr1-x(OH)3, Cr2O3, and FeCr2O4 by biotic Fe0. Reoxidation experiment revealed that these products exhibited superior stability to the immobilized products generated by Fe0 or bacteria. Additionally, organic acid concentration and Fe0 dosage showed significantly positive correlation with Cr(VI) removal within the range of biological adaptation, which emphasized that heterotrophic and autotrophic bacteria acted essential roles in Cr(VI) removal. This work highlighted the enhanced effect of heterotrophic and autotrophic activities on Cr(VI) reduction and stabilization by Fe0 and offered a promising approach for bioleached wastewater treatment.


Subject(s)
Bacteria , Chromium , Iron , Wastewater , Wastewater/chemistry , Iron/chemistry , Iron/metabolism , Chromium/metabolism , Chromium/chemistry , Bacteria/metabolism , Autotrophic Processes , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/chemistry , Adsorption
5.
J Clin Nurs ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38924233

ABSTRACT

AIMS: This study aims to develop an evidence-based nursing practice program to prevent unplanned endotracheal extubation (UEE) among adult patients in the intensive care unit (ICU). DESIGN: This study uses the Delphi method to develop an evidence-based nursing practice program. METHODS: A comprehensive review of 18 databases and evidence-based websites was conducted to gather, assess and synthesize evidence on preventing UEEs in adult patients. Using this synthesized evidence, a questionnaire was formulated for further investigation. Subsequently, input was solicited from experts through Delphi surveys to establish an evidence-based nursing practice protocol for preventing UEEs in adult ICU patients. Consistency in consultation results guided subsequent rounds of consultation. RESULTS: The developed program comprised 43 evidence items categorized into nine dimensions, including risk assessment for unplanned extubation, sedation, analgesia, delirium, balloon management, psychosocial care, early extubation, catheter immobilization and protective restraints. Two rounds of expert inquiry yielded recovery rates of 94.7% and 100% for the first and second questionnaires, respectively. Kendall W values ranged from .224 to .353 (p < .001). CONCLUSION: This study developed an evidence-based nursing practice program to prevent UEE in adult ICU patients, employing evidence-based practices and Delphi expert consultation methods. However, further validation of the program's effectiveness is warranted. REPORTING METHOD: Findings were reported according to the Standards for Reporting Qualitative Research checklist. PATIENT OR PUBLIC CONTRIBUTION: Nurses contributed to the study by participating in investigations. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: The program developed in this study offers an evidence-based framework for preventing unplanned extubation in hospitals, thereby reducing its incidence and enhancing the quality of nursing care.

6.
J Environ Manage ; 363: 121411, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38861887

ABSTRACT

Rural areas are the main source of ecosystem services in arid and semi-arid areas, and ecosystem services are the background conditions for rural revitalization. In this study, the spatial pattern of key ecosystem services in the countryside was assessed, and the trade-offs and synergistic relationships among ecosystem services were investigated, using the Tacheng-Emin Basin in China as the study area. Finally, the types of ecological function zoning and development strategies for the countryside are proposed. The results showed that: (1) the area of ecological land was large, and the average land use intensity was 2.48, which belonged to the medium intensity. (2) The mean values of the six ecosystem services are all in the middle and lower classes, and the spatial distribution of the five ecosystem services is similar, except for food production. (3) Except for grain production, the other five ecosystem services showed positive feedback to elevation. The other five ecosystem services are synergistic, and there are trade-offs between grain production and other ecosystem services. In the nonlinear interaction mechanism of ecosystem services, the fluctuation constraint occupies the largest proportion. (4) At smaller spatial scales, there are more types of ecosystem service clusters. Combining the results of the study, the villages in the study area can be categorized into five types. This study formulates five priority levels of rural ecological revitalization and proposes different development recommendations for the sustainable development of each type of village. This study is helpful for the fine management of land resources and the revitalization of rural ecology and provides a reference for the sustainable development of ecosystem services in arid and semi-arid areas.


Subject(s)
Conservation of Natural Resources , Ecosystem , China , Ecology
7.
iScience ; 27(6): 110129, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38904068

ABSTRACT

Integrin-dependent crosstalk between cell-matrix adhesions and cell-cell junctions is critical for controlling endothelial permeability and proliferation in cancer and inflammatory diseases but remains poorly understood. Here, we investigated how acetylation of the distal NPKY-motif of Integrin-ß1 influences endothelial cell physiology and barrier function. Expression of an acetylation-mimetic ß1-K794Q-GFP mutant led to the accumulation of immature cell-matrix adhesions accompanied by a transcriptomic reprograming of endothelial cells, involving genes associated with cell adhesion, proliferation, polarity, and barrier function. ß1-K794Q-GFP induced constitutive MAPK signaling, junctional impairment, proliferation, and reduced contact inhibition at confluence. Structural analysis of Integrin-ß1 interaction with KINDLIN2, biochemical pulldown assay, and binding energy determination by using molecular dynamics simulation showed that acetylation of K794 and the K794Q-mutant increased KINDLIN2 binding affinity to the Integrin-ß1. Thus, enhanced recruitment of KINDLIN2 to Lysine-acetylated Integrin-ß1 and resulting modulation of barrier function, offers new therapeutic possibilities for controlling vascular permeability and disease conditions.

8.
J Environ Manage ; 362: 121327, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38824892

ABSTRACT

In this study, nanoscale cupric oxide-decorated activated carbon (nCuO@AC) was synthesized by impregnation-calcination and employed to assist the decomposition of H2O2 for effective sterilization with Escherichia coli as target bacteria. Characteristic technologies demonstrated that copper oxide particles of 50-100 nm were uniformly distributed on AC surface. Owing to electron transfer from hydroxyl and aldehyde to CuO on AC, surface-bonded Cu(II) was partially reduced to Cu(I) in the nCuO matrix. The resultant Cu(I) expedited the decomposition of H2O2 and converted it into ·OH radicals which were identified by quenching experiment and electron paramagnetic resonance test. Due to oxidation attack of generated ·OH, the nCuO@AC-H2O2 system achieved a much higher inactivation rate of 6.0 log within 30 min as compared to those of 2.1 and 1.3 log in the nCuO@AC and nCuO-H2O2 systems. It also exhibited excellent pH adaptability and high inactivation efficiency under neutral conditions. After four cycles, the nCuO@AC-H2O2 system could still inactivate 5.5 log bacteria, indicating excellent stability and reusability of nCuO@AC. Spent nCuO@AC could be regenerated by eluting surficial copper oxides with hydrochloric acid, and re-coating nCuO particles through impregnation-calcination with a regeneration rate of 96.6%. Our results demonstrated that nCuO@AC was an efficient and prospective catalyst to assist the decomposition of H2O2 for effective inactivation of bacteria in water.


Subject(s)
Charcoal , Copper , Escherichia coli , Hydrogen Peroxide , Escherichia coli/drug effects , Hydrogen Peroxide/chemistry , Copper/chemistry , Charcoal/chemistry , Carbon/chemistry , Oxidation-Reduction
9.
J Natl Cancer Inst ; 116(8): 1356-1365, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38702830

ABSTRACT

BACKGROUND: TP53 alterations are common in certain pediatric cancers, making identification of putative germline variants through tumor genomic profiling crucial for disease management. METHODS: We analyzed TP53 alterations in 3123 tumors from 2788 pediatric patients sequenced using tumor-only or tumor-normal paired panels. Germline confirmatory testing was performed when indicated. Somatic and germline variants were classified based on published guidelines. RESULTS: In 248 tumors from 222 patients, 284 tier 1/2 TP53 sequence and small copy number variants were detected. Following germline classification, 86.6% of 142 unique variants were pathogenic or likely pathogenic. Confirmatory testing on 118 patients revealed germline TP53 variants in 28 of them (23 pathogenic or likely pathogenic and 5 of uncertain significance), suggesting a minimum Li-Fraumeni syndrome incidence of 0.8% (23/2788) in this cohort, 10.4% (23/222) in patients with TP53 variant-carrying tumors, and 19.5% (23/118) with available normal samples. About 25% (7/28) of patients with germline TP53 variants did not meet Li-Fraumeni syndrome diagnostic or testing criteria, while 20.9% (28/134) with confirmed or inferred somatic origins did. TP53 biallelic inactivation occurred in 75% of germline carrier tumors and was also prevalent in other groups, causing an elevated tumor-observed variant allelic fraction. Somatic evidence, however, including low variant allele fraction correctly identified only 27.8% (25/90) of patients with confirmed somatic TP53 variants. CONCLUSION: The high incidence and variable phenotype of Li-Fraumeni syndrome in this cohort highlights the importance of assessing germline status of TP53 variants identified in all pediatric tumors. Without clear somatic evidence, distinguishing somatic from germline origins is challenging. Classifying germline and somatic variants should follow appropriate guidelines.


Subject(s)
Germ-Line Mutation , Li-Fraumeni Syndrome , Neoplasms , Tumor Suppressor Protein p53 , Humans , Tumor Suppressor Protein p53/genetics , Child , Li-Fraumeni Syndrome/genetics , Li-Fraumeni Syndrome/epidemiology , Neoplasms/genetics , Neoplasms/epidemiology , Male , Female , Child, Preschool , Adolescent , Genetic Predisposition to Disease , DNA Copy Number Variations , Genetic Testing/methods , Prevalence , Infant
10.
Sci Rep ; 14(1): 11902, 2024 05 24.
Article in English | MEDLINE | ID: mdl-38789502

ABSTRACT

A significant number of intensive care unit (ICU) survivors experience new-onset functional impairments that impede their activities of daily living (ADL). Currently, no effective assessment tools are available to identify these high-risk patients. This study aims to develop an interpretable machine learning (ML) model for predicting the onset of functional impairment in critically ill patients. Data for this study were sourced from a comprehensive hospital in China, focusing on adult patients admitted to the ICU from August 2022 to August 2023 without prior functional impairments. A least absolute shrinkage and selection operator (LASSO) model was utilized to select predictors for inclusion in the model. Four models, logistic regression, support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost), were constructed and validated. Model performance was assessed using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Additionally, the DALEX package was employed to enhance the interpretability of the final models. The study ultimately included 1,380 patients, with 684 (49.6%) exhibiting new-onset functional impairment on the seventh day after leaving the ICU. Among the four models evaluated, the SVM model demonstrated the best performance, with an AUC of 0.909, accuracy of 0.838, sensitivity of 0.902, specificity of 0.772, PPV of 0.802, and NPV of 0.886. ML models are reliable tools for predicting new-onset functional impairments in critically ill patients. Notably, the SVM model emerged as the most effective, enabling early identification of patients at high risk and facilitating the implementation of timely interventions to improve ADL.


Subject(s)
Activities of Daily Living , Critical Illness , Intensive Care Units , Humans , Male , Female , Middle Aged , Aged , Machine Learning , China/epidemiology , Support Vector Machine , Adult , Patient Transfer , Logistic Models
11.
Microorganisms ; 12(5)2024 May 10.
Article in English | MEDLINE | ID: mdl-38792792

ABSTRACT

To gain an in-depth understanding of the diversity and composition of soil Acidobacteria in five different forest types in typical temperate forest ecosystems and to explore their relationship with soil nutrients. The diversity of soil Acidobacteria was determined by high-throughput sequencing technology. Soil Acidobacteria's alpha-diversity index and soil nutrient content differed significantly among different forest types. ß-diversity and the composition of soil Acidobacteria also varied across forest types. Acidobacterial genera, such as Acidobacteria_Gp1, Acidobacteria_Gp4, and Acidobacteria_Gp17, play key roles in different forests. The RDA analyses pointed out that the soil pH, available nitrogen (AN), carbon to nitrogen (C/N) ratio, available phosphorus (AP), total carbon (TC), and total phosphorus (TP) were significant factors affecting soil Acidobacteria in different forest types. In this study, the diversity and composition of soil Acidobacteria under different forest types in a temperate forest ecosystem were analyzed, revealing the complex relationship between them and soil physicochemical properties. These findings not only enhance our understanding of soil microbial ecology but also provide important guidance for ecological conservation and restoration strategies for temperate forest ecosystems.

12.
Plants (Basel) ; 13(10)2024 May 09.
Article in English | MEDLINE | ID: mdl-38794375

ABSTRACT

Calcium ions function as key messengers in the context of intracellular signal transduction. The ability of plants to respond to biotic and abiotic stressors is highly dependent on the calcineurin B-like protein (CBL) and CBL-interacting protein kinase (CIPK) signaling network. Here, a comprehensive effort was made to identify all members of the soybean CBL gene family, leading to the identification of 15 total genes distributed randomly across nine chromosomes, including 13 segmental duplicates. All the GmCBL gene subfamilies presented with similar gene structures and conserved motifs. Analyses of the expression of these genes in different tissues revealed that the majority of these GmCBLs were predominantly expressed in the roots. Significant GmCBL expression and activity increases were also observed in response to a range of stress-related treatments, including salt stress, alkaline stress, osmotic stress, or exposure to salicylic acid, brassinosteroids, or abscisic acid. Striking increases in GmCBL1 expression were observed in response to alkaline and salt stress. Subsequent analyses revealed that GmCBL1 was capable of enhancing soybean salt and alkali tolerance through the regulation of redox reactions. These results offer new insight into the complex mechanisms through which the soybean CBL gene family regulates the responses of these plants to environmental stressors, highlighting promising targets for efforts aimed at enhancing soybean stress tolerance.

13.
Biol Reprod ; 111(1): 212-226, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38531779

ABSTRACT

Pigs serve as a robust animal model for the study of human diseases, notably in the context of disorders of sex development (DSD). This study aims to investigate the phenotypic characteristics and molecular mechanisms underlying the reproductive and developmental abnormalities of 38,XX ovotestis-DSD (OT-DSD) and 38,XX testis-DSD (T-DSD) in pigs. Clinical and transcriptome sequencing analyses were performed on DSD and normal female pigs. Cytogenetic and SRY analyses confirmed that OT/T-DSD pigs exhibited a 38,XX karyotype and lacked the SRY gene. The DSD pigs had higher levels of follicle-stimulating hormone, luteinizing hormone, and progesterone, but lower testosterone levels when compared with normal male pigs. The reproductive organs of OT/T-DSD pigs exhibit abnormal development, displaying both male and female characteristics, with an absence of germ cells in the seminiferous tubules. Sex determination and development-related differentially expressed genes shared between DSD pigs were identified in the gonads, including WT1, DKK1, CTNNB1, WTN9B, SHOC, PTPN11, NRG1, and NXK3-1. DKK1 is proposed as a candidate gene for investigating the regulatory mechanisms underlying gonadal phenotypic differences between OT-DSD and T-DSD pigs. Consequently, our findings provide insights into the molecular pathogenesis of DSD pigs and present an animal model for studying into DSD in humans.


Subject(s)
Gene Expression Profiling , Transcriptome , Animals , Swine/genetics , Female , Male , Swine Diseases/genetics , Swine Diseases/metabolism , Disorders of Sex Development/genetics , Disorders of Sex Development/veterinary , Testis/metabolism , Gonads/metabolism
14.
J Nutr ; 154(4): 1262-1270, 2024 04.
Article in English | MEDLINE | ID: mdl-38367806

ABSTRACT

BACKGROUND: The relationship between whole grain intake and chronic kidney disease (CKD) remains uncertain. OBJECTIVE: This study aimed to evaluate the association between whole grain intake and risk of CKD in Chinese adults. METHODS: The present cross-sectional study used data from the China Health and Nutrition Survey conducted in 2009. Whole grain intake was measured using 3 consecutive 24-h dietary recalls and a household food inventory. A multivariable logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of CKD. In addition, a restricted cubic spline was used to investigate the dose‒response relationship between whole grain and risk of CKD. RESULTS: A total of 6747 participants were included, 728 of whom had CKD. Compared with those in the lowest whole grain intake group, those in the higher grain intake group had an inverse association with risk of CKD (Q2: adjusted OR 0.70, 95% CI: 0.54, 0.89; Q3: adjusted OR 0.54, 95% CI: 0.42, 0.69; and Q4: adjusted OR 0.29, 95% CI: 0.21, 0.41). The association between whole grain intake and CKD seems to be stronger for individuals who were male (P for interaction = 0.008) or smokers (P for interaction = 0.013). In addition, the restricted cubic spline suggested an obvious L-shaped correlation. CONCLUSIONS: Increased whole grain intake was associated with a decreased risk of CKD in Chinese adults.


Subject(s)
Renal Insufficiency, Chronic , Whole Grains , Adult , Humans , Male , Female , Cross-Sectional Studies , Renal Insufficiency, Chronic/epidemiology , Diet , Nutrition Surveys
15.
J Transl Med ; 22(1): 164, 2024 02 16.
Article in English | MEDLINE | ID: mdl-38365806

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by complement dependent and proinflammatory activation of macrophages. However, effective treatment for complement activation in PAH is lacking. We aimed to explore the effect and mechanism of CP40-KK (a newly identified analog of selective complement C3 inhibitor CP40) in the PAH model. METHODS: We used western blotting, immunohistochemistry, and immunofluorescence staining of lung tissues from the monocrotaline (MCT)-induced rat PAH model to study macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Surface plasmon resonance (SPR), ELISA, and CH50 assays were used to test the affinity between CP40-KK and rat/human complement C3. CP40-KK group rats only received CP40-KK (2 mg/kg) by subcutaneous injection at day 15 to day 28 continuously. RESULTS: C3a was significantly upregulated in the plasma of MCT-treated rats. SPR, ELISA, and CH50 assays revealed that CP40-KK displayed similar affinity binding to human and rat complement C3. Pharmacological inhibition of complement C3 cleavage (CP40-KK) could ameliorate MCT-induced NLRP3 inflammasome activity, pulmonary vascular remodeling, and right ventricular hypertrophy. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cells is closely associated with macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Besides, C3a enhanced IL-1ß activity in macrophages and promoted pulmonary arterial smooth muscle cell proliferation in vitro. CONCLUSION: Our findings suggest that CP40-KK treatment was protective in the MCT-induced rat PAH model, which might serve as a therapeutic option for PAH.


Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Rats , Humans , Animals , Pulmonary Arterial Hypertension/drug therapy , Inflammasomes/metabolism , Interleukin-18/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Complement C3/metabolism , Complement Inactivating Agents/adverse effects , Complement Inactivating Agents/metabolism , Pulmonary Artery/metabolism , Cytokines/metabolism , Disease Models, Animal
17.
Chemosphere ; 352: 141391, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38325615

ABSTRACT

Zero-valent iron (ZVI), as an effective medium, is widely used to eliminate heavy metal ions in filter tanks. However, it will react with Cr(VI) to generate Fe-Cr precipitates with low conductivity on its surface, resulting in slow iron corrosion and low Cr(VI) removal efficiency. In this study, three oxidants (KMnO4, NaClO, and Na2S2O8) were employed to promote iron corrosion in ZVI systems for enhanced Cr(VI) removal at a concentration of 5 mg/L through batch tests and column experiments. The ZVI/KMnO4, ZVI/NaClO, and ZVI/Na2S2O8 systems achieved significantly higher Cr(VI) removal rates of 31.5%, 52.8%, and 65.9% than the ZVI system (9.8%). Solid phase characterization confirmed that these improvements were attributed to promoted iron corrosion and secondary mineral formation (e.g., lepidocrocite, ferrihydrite, and magnetite) by oxidants. Those minerals offered more reaction sites for Cr(VI) reduction, adsorption, and sequestration. Cycle experiments indicated that ZVI/oxidant systems could stably remove Cr(VI). In long-term column experiment, the ZVI/NaClO column showed a much longer life-span and exhibited a 34.8 times higher Cr(VI) removal capacity than that of the ZVI column. These findings demonstrated that ZVI in combination with a reasonable amount of oxidants was a promising method for removing Cr(VI) in practical filter tanks and provided a new insight to enhance Cr(VI) removal.


Subject(s)
Iron , Water Pollutants, Chemical , Oxidants , Corrosion , Chromium/analysis
18.
Environ Res ; 248: 118253, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38278507

ABSTRACT

A weak electric field (WEF, 2 mA cm-2) was employed to promote Fe(III)/Fe(II) cycle on goethite-impregnated activated carbon (FeOOH@AC) filled in a continuous-flow column for enhanced Cr(VI) elimination from water. Surficial analysis and Cr species distribution showed that α-FeOOH of 0.2-1 µm was successfully synthesized and evenly loaded onto AC. Electron transfer from WEF to α-FeOOH was facilitated with AC as electron shuttles, thereby boosting Fe(III) reduction in the α-FeOOH. The generated Fe(II) reduced Cr(VI) and the resultant Cr(III) subsequently precipitated with OH- and Fe(III) to form Cr(OH)3 and (CrχFe1-χ)(OH)3. Therefore, the WEF-FeOOH@AC column exhibited a much lower Cr(VI) migration rate of 0.0018 cm PV-1 in comparison with 0.0037 cm PV-1 of the FeOOH@AC column, equal to 104 % higher Cr(VI) elimination capacity and 90 % longer column service life-span. Additionally, under different Cr(VI) loadings by varying either seepage velocities or influent Cr(VI) concentrations, the WEF-FeOOH@AC column maintained 1.0-1.5 folds higher Cr(VI) elimination and 0.9-1.4 folds longer longevity than those of the FeOOH@AC column owing to the interaction between FeOOH@AC and WEF. Our research demonstrated that WEF-FeOOH@AC was a potential method to promote Cr(VI) elimination from water and offer an effective strategy to facilitate Fe(III)/Fe(II) cycle in iron oxides.


Subject(s)
Ferric Compounds , Iron Compounds , Minerals , Water Pollutants, Chemical , Water , Charcoal , Oxidation-Reduction , Chromium/analysis , Water Pollutants, Chemical/analysis , Ferrous Compounds
19.
Mitochondrial DNA B Resour ; 9(1): 33-36, 2024.
Article in English | MEDLINE | ID: mdl-38187011

ABSTRACT

Rhamnus leptacantha C.K.Schneid. (1914). is a rare shrub species of the genus Rhamnus. The complete plastid genome of Rhamnus leptacantha was sequenced for the first time in this study. The total length of this genome is 161,248 bp with a large single copy (LSC) region (89,386 bp), a small single copy (SSC) region (19,000 bp), and two inverted repeat regions (IRs, 26,431 bp). A total of 133 functional genes were annotated, including 88 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Plastome of R. leptacantha displayed a conservative structure and gene order. Phylogenetic analysis strongly supported R. leptacantha clustered with other members of genus Rhamnus. This study provides a foundation for further investigation of the complete chloroplast genome in inferring the evolution within the Rhamnaceae family.

20.
STAR Protoc ; 5(1): 102850, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38285735

ABSTRACT

Circular dichroism (CD) spectrometry is a rapid technique for detecting protein secondary structure, particularly helicity. DMSO is used to ensure optimal solubility of peptides/peptidomimetics; however, its background absorbance hinders effective CD analysis. Here, we present a protocol for reconstituting peptides/peptidomimetics from DMSO to aqueous buffers for CD analyses. We describe steps for identifying chemicals that induce DMSO evaporation, extracting peptides/peptidomimetics from DMSO, and CD spectrometer setup and analysis. We then detail procedures for secondary structure analyses of reconstituted peptides/peptidomimetics. For complete details on the use and execution of this protocol, please refer to Gao et al. (2023).1.


Subject(s)
Dimethyl Sulfoxide , Peptidomimetics , Circular Dichroism , Dimethyl Sulfoxide/chemistry , Peptides/chemistry , Proteins , Water
SELECTION OF CITATIONS
SEARCH DETAIL