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1.
Sci Total Environ ; 947: 174469, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38972419

ABSTRACT

Understanding the transformation process of dissolved organic matter (DOM) in the sewer is imperative for comprehending material circulation and energy flow within the sewer. The machine learning (ML) model provides a feasible way to comprehend and simulate the DOM transformation process in the sewer. In contrast, the model accuracy is limited by data restriction. In this study, a novel framework by integrating generative adversarial network algorithm-machine learning models (GAN-ML) was established to overcome the drawbacks caused by the data restriction in the simulation of the DOM transformation process, and humification index (HIX) was selected as the output variable to evaluate the model performance. Results indicate that the GAN algorithm's virtual dataset could generally enhance the simulation performance of regression models, deep learning models, and ensemble models for the DOM transformation process. The highest prediction accuracy on HIX (R2 of 0.5389 and RMSE of 0.0273) was achieved by the adaptive boosting model which belongs to ensemble models trained by the virtual dataset of 1000 samples. Interpretability analysis revealed that dissolved oxygen (DO) and pH emerge as critical factors warranting attention for the future development of management strategies to regulate the DOM transformation process in sewers. The integrated framework proposed a potential approach for the comprehensive understanding and high-precision simulation of the DOM transformation process, paving the way for advancing sewer management strategy under data restriction.

2.
Eur Radiol ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834788

ABSTRACT

OBJECTIVES: To investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) for evaluating pulmonary artery (PA) masses, and compare it with [18F]fluorodeoxyglucose (FDG) PET/CT. METHODS: Participants with clinically suspected PA malignancy were prospectively enrolled and underwent dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging. Visual analysis and semi-quantitative parameters were compared between the two types of radiotracers. The tissue specimen underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS: Thirty-three patients (18 males/15 females; mean age 53.1 ± 15.4 years) were enrolled. All 21 patients with malignant PA masses were FDG-positive (100%), whereas 20 out of 21 patients were FAPI-positive (95.2%). All 12 patients with benign PA masses were both negative in FDG and FAPI PET. The mean maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) of FAPI and FDG in malignant PA masses were significantly higher than those of benign masses. Although there was no significant difference in SUVmax between FDG and FAPI in malignant PA masses (11.36 vs. 9.18, p = 0.175), the TBR (liver) and TBR (left ventricle) were more favorable for FAPI than for FDG (13.04 vs. 5.17, p < 0.001); (median: 7.75 vs. 2.75, p = 0.007). Immunohistochemical analysis (n = 16) validated that the level of FAP expression corresponded strongly to the uptake of FAPI in PET/CT scans (rs = 0.712, p = 0.002). For clinical management, FAPI PET found more metastatic lesions than FDG PET in 4 patients, with 2 patients upgrading and 1 patient changing treatment decisions. CONCLUSIONS: FAPI PET/CT is feasible in the diagnosis of PA masses. Although not superior to FDG PET/CT, FAPI PET/CT showed better target-to-background contrast. CLINICAL RELEVANCE STATEMENT: This study found that FAPI PET/CT is not superior to FDG PET/CT in diagnosing PA masses, but FAPI PET/CT displays better target-to-background contrast and more positive lesions, which may help improve disease management. KEY POINTS: Pulmonary malignancies lack specificity in clinical manifestations, laboratory tests, and routine imaging examinations. FAPI PET/CT is not diagnostically better than FDG PET/CT but displays better target-to-background contrast and more positive lesions. Dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging improves clinical management of pulmonary artery masses.

3.
BMC Pulm Med ; 24(1): 265, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38825688

ABSTRACT

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. METHODS AND DESIGN: The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. CONCLUSIONS: As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT05311072.


Subject(s)
Angioplasty, Balloon , Endarterectomy , Hypertension, Pulmonary , Pulmonary Embolism , Humans , Hypertension, Pulmonary/therapy , China , Pulmonary Embolism/complications , Pulmonary Embolism/therapy , Chronic Disease , Quality of Life , Treatment Outcome , Female , Combined Modality Therapy , Male , East Asian People
4.
Water Res ; 259: 121851, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38851110

ABSTRACT

Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies.


Subject(s)
Anti-Bacterial Agents , Ciprofloxacin , Denitrification , Ciprofloxacin/pharmacology , Anti-Bacterial Agents/pharmacology , Paracoccus denitrificans/metabolism
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 841-846, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926977

ABSTRACT

OBJECTIVE: To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA). METHODS: The clinical data of children diagnosed with AA and treated with CsA alone from January 1, 2016 to December 31, 2020 in the Children's Hospital of Chongqing Medical University were collected, and the efficacy and influencing factors of CsA treatment were evaluated. RESULTS: Among the 119 patients, there were 62 male and 57 female, with a median age of 7 years and 1 month. There were 45 cases of very severe AA (VSAA), 47 cases of severe AA (SAA), and 27 cases of non-severe AA (NSAA). At 6 months after treatment, the efficacy of VSAA was lower than that of SAA and NSAA, and there was a statistical difference (P < 0.01). 6 cases died early, 16 cases relapsed, 2 cases progressed to AML and ALL. The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA, while high PLT count was a protective factor (P =0.008, P =0.002). The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5×109 /L, 68.5%, respectively. Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST (P =0.020, OR =0.062), and high PLT count was a protective factor (P =0.044, OR =1.038). At 3 months of treatment, CsA response and NSAA were the risk factor for recurrence (P =0.001, 0.031). CONCLUSION: The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone. A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA, and a high proportion of bone marrow lymphocyte was an unfavorable factor. CsA response at 3 months and NSAA were risk factors for recurrence.


Subject(s)
Anemia, Aplastic , Cyclosporine , Humans , Anemia, Aplastic/drug therapy , Cyclosporine/therapeutic use , Female , Male , Child , Treatment Outcome , Platelet Count , Immunosuppressive Agents/therapeutic use , Child, Preschool , Adolescent , Bone Marrow
6.
J Am Chem Soc ; 146(20): 13719-13726, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38721780

ABSTRACT

With increasing interest in constructing more three-dimensional entities, there has been growing interest in cross-coupling reactions that forge C(sp3)-C(sp3) bonds, which leads to additional challenges as it is not just a more difficult bond to construct but issues of stereocontrol also arise. Herein, we report the stereocontrolled cross-coupling of enantioenriched boronic esters with racemic allylic carbonates enabled by iridium catalysis, leading to the formation of C(sp3)-C(sp3) bonds with single or vicinal stereogenic centers. The method shows broad substrate scope, enabling primary, secondary, and even tertiary boronic esters to be employed, and can be used to prepare any of the four possible stereoisomers of a coupled product with vicinal chiral centers. The new method, which combines the simultaneous enantiospecific reaction of a chiral nucleophile with the enantioselective reaction of a chiral electrophile in a single process, offers a solution for stereodivergent cross-coupling of two C(sp3) fragments.

7.
Thromb Haemost ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38729190

ABSTRACT

BACKGROUND: The extent to which educational attainment (EA) influences the risk of varicose veins (VVs), venous thromboembolism (VTE), and phlebitis occurrence, whether this pathway is mediated by obesity-related traits, and the proportion of their mediation is unknown. METHODS: A Mendelian randomization (MR) design was used to genetically investigate the causal effects of EA on the risk of VV, VTE, and phlebitis and to assess the mediating effect of obesity-related traits. Causal effects were estimated using primarily the multiplicative random-effects inverse variance-weighted method. This was supplemented by Cochran's Q-statistic, MR-Egger regression, MR funnel plots, and leave-one-out test to evaluate the reliability of the results. For the individual mediation effect, the coefficient product method was mainly utilized to estimate. RESULTS: An increase in genetically predicted EA was associated with a lower risk of VV, VTE, and phlebitis, as well as lower body mass index, basal metabolic rate, hip circumference, and waist circumference. As genetically predicted body mass index, basal metabolic rate, hip circumference, and waist circumference increased, the risk of developing VV, VTE, and phlebitis increased, respectively. Body mass index, basal metabolic rate, hip circumference, and waist circumference were identified as mediators of the protective effects of EA on VV, VTE, and phlebitis. CONCLUSION: The findings support a causal relationship between higher EA and lower risk of VV, VTE, and phlebitis. Obesity-related traits play a significant mediating role in these pathways, and there are interactions between them, with hip circumference mediating these pathways relatively independently from the other three.

8.
Plant Dis ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783581

ABSTRACT

Celosia spp. is a widely cultivated ornamental plant in gardens or parks in Taiwan. In September 2021, withering leaves and grayish-brown lesions were observed on the lower stem of plumed cockscombs (C. argentea var. plumosa) in Taichung City, with an incidence of about 22% in 136 plants after continuous precipitation, impacting the aesthetic value of the landscape. Symptomatic plants were collected, surface disinfected with 70% EtOH for ~20 sec., blotted dried, and excised diseased tissues (~ 3×3 mm2) were placed on 2% water agar. Four representative isolates were obtained after purification and the colonies were white with aerial and non-septated hyphae on V8 agar for 7 days. Sporangia were ovoid, ellipsoid or obpyriform, papillate, (26.3-55.9) 38.0 × 29.0 (20.1-40.6) µm (n = 200) (Ahonsi et al. 2007). Chlamydospores were spherical, terminal or intercalary, 26.0 (15.1-40.4) µm (n = 200). All isolates belong to A2 mating type with amphigynous antheridia and plerotic oospores, 21.0 (17.7-25.7) µm (n = 200), resembling the descriptions of Phytophthora (Erwin & Ribeiro 1996). For molecular identification, sequences of the ITS, ß-tubulin (ß-tub), and EF-1α regions of all isolates were amplified using ITS1/ITS4, TUBUF2/TUBUR1, and ELONGF1/ELONGR1 primers, respectively (White et al. 1990; Kroon et al. 2004). BLAST analyses of isolates cap1-2 (ITS: OQ581785; ß-tub: OQ590022; EF-1α: OQ590026), cap1-3 (ITS: OQ581786; ß-tub: OQ590023; EF-1α: OQ590027), cap2-1 (ITS: OQ581787; ß-tub: OQ590024; EF-1α: OQ590028), and cap2-2 (ITS: OQ581788; ß-tub: OQ590025; EF-1α: OQ590029) showed 100% of ITS identity, 99.5 to 99.9% of ß-tub identity, and 99.4 to 99.6% of EF-1α identity with Phytophthora nicotianae (ITS: MG865551; ß-tub: MH493987; EF-1α: MH359043). Phylogenetic trees were constructed using concatenated ITS, ß-tub, and EF-1α sequences based on maximum likelihood with a GTR+G model in MEGA X and Bayesian inference method in Geneious Prime 2022.2. All isolates were clustered in P. nicotianae with similar topology, thereby were identified as P. nicotianae. To confirm pathogenicity, 7 to 10-day-old seedlings and 6-week-old plumed cockscomb plants were inoculated in separate trials and each experiment was conducted twice. For each seedling, the lower stem was inoculated with 50 µl of zoospore suspension (104 zoospores/ml), 3 plants per isolate, and then incubated at 30±2℃ with 12 h light. For adult plants, each was inoculated with mycelial plugs from one V8 plate of 10-day-old P. nicotianae, 5 plants per isolate, and incubated at 25±2℃ in a greenhouse. Control plants were inoculated with sterile water and V8 agar plugs, respectively. Stem and root rot were observed on seedlings 4 days after inoculation while wilting and lower stem browning were observed on adult plants 2 months after inoculation. All control plants remained healthy at the end of repeated trials and identical pathogens were re-isolated only from symptomatic plants, thus fulfilling Koch's rules. P. nicotianae has been reported causing root rot and stem necrosis not only on cockscomb (C. plumosa Hort. ex Burvenich) in Argentina (Frezzi 1950), but also infecting several ornamental plants recently in Taiwan (Ann et al. 2018). To our knowledge, this is the first report of stem blight caused by P. nicotianae on plumed cockscombs in Taiwan. This finding suggests limited options for landscaping and the host preference of the isolates obtained in this study should warrant further studies.

9.
World J Gastrointest Surg ; 16(5): 1328-1335, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38817299

ABSTRACT

BACKGROUND: Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma (CRC) and their association with lymph node metastasis (LNM). Therefore, more relevant studies and analyses need to be conducted. AIM: To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM. METHODS: This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023. Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1. The correlation of the two genes with patients' clinicopathological data (e.g., LNM) was explored, and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC. RESULTS: Significantly higher positive rates and expression levels of GLI1 and PTTG1 were observed in CRC tissue samples compared with adjacent tissues. GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC, with higher GLI1 and PTTG1 levels found in patients with LNM than in those without. The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811, respectively. CONCLUSION: GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients. Moreover, high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery. The expression of both genes has certain diagnostic and therapeutic significance.

10.
J Asian Nat Prod Res ; : 1-12, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753582

ABSTRACT

Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds 6j (29.73 µg/ml) and 7a (38.15 µg/ml) displayed excellent inhibitory activity against the spore of Fusarium solani. The inhibitory activity of compound 7d (10.53 µg/ml) against the spore of Alternaria solani was more than 42-fold that of vanillin. Compound 7a (37.54 µg/ml) showed better antifungal activity against the spore of B. cinerea than positive controls. The cytotoxicity assay confirmed that compounds 6k, 7a, and 7d showed good selectivity and less toxicity to normal mammalian cells.

11.
Water Res ; 258: 121778, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38795549

ABSTRACT

Biotechnology for wastewater treatment is mainstream and effective depending upon microbial redox reactions to eliminate diverse contaminants and ensure aquatic ecological health. However, refractory organic nitrogen compounds (RONCs, e.g., nitro-, azo-, amide-, and N-heterocyclic compounds) with complex structures and high toxicity inhibit microbial metabolic activity and limit the transformation of organic nitrogen to inorganic nitrogen. This will eventually result in non-compliance with nitrogen discharge standards. Numerous efforts suggested that applying exogenous electron donors or acceptors, such as solid electrodes (electrostimulation) and limited oxygen (micro-aeration), could potentially regulate microbial redox reactions and catabolic pathways, and facilitate the biotransformation of RONCs. This review provides comprehensive insights into the microbial regulation mechanisms and applications of electrostimulation and micro-aeration strategies to accelerate the biotransformation of RONCs to organic amine (amination) and inorganic ammonia (ammonification), respectively. Furthermore, a promising approach involving in-situ hybrid anaerobic biological units, coupled with electrostimulation and micro-aeration, is proposed towards engineering applications. Finally, employing cutting-edge methods including multi-omics analysis, data science driven machine learning, technology-economic analysis, and life-cycle assessment would contribute to optimizing the process design and engineering implementation. This review offers a fundamental understanding and inspiration for novel research in the enhanced biotechnology towards RONCs elimination.


Subject(s)
Nitrogen , Oxidation-Reduction , Wastewater , Wastewater/chemistry , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/metabolism
12.
Sci Rep ; 14(1): 12431, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38816406

ABSTRACT

Pulmonary arterial hypertension (PAH) is a fatal disease featured by high morbidity and mortality. Although Cordycepin is known for its anti-inflammatory, antioxidant and immune-enhancing effects, its role in PAH treatment and the underlying mechanisms remain unclear. The therapeutic effects of Cordycepin on rats with PAH were investigated using a monocrotaline (MCT)-induced rat model. The metabolic effects of Cordycepin were assessed based on the plasma metabolome. The potential mechanisms of Cordycepin in PAH treatment were investigated through transcriptome sequencing and validated in pulmonary artery smooth muscle cells (PASMC). Evaluations included hematoxylin and eosin staining for pulmonary vascular remodeling, CCK-8 assay, EDU, and TUNEL kits for cell viability, proliferation, and apoptosis, respectively, and western blot for protein expression. Cordycepin significantly reduced right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in PAH rats, and mitigated pulmonary vascular remodeling. Plasma metabolomics showed that Cordycepin could reverse the metabolic disorders in the lungs of MCT-induced PAH rats, particularly impacting linoleic acid and alpha-linolenic acid metabolism pathways. Transcriptomics revealed that the P53 pathway might be the primary pathway involved, and western blot results showed that Cordycepin significantly increased P53 and P21 protein levels in lung tissues. Integrated analysis of transcriptomics and metabolomics suggested that these pathways were mainly enriched in linoleic acid metabolism and alpha-linolenic acid metabolism pathway. In vitro experiments demonstrated that Cordycepin significantly inhibited the PDGFBB (PD)-induced abnormal proliferation and migration of PASMC and promoted PD-induced apoptosis. Meanwhile, Cordycepin enhanced the expression levels of P53 and P21 proteins in PD-insulted PASMC. However, inhibitors of P53 and P21 eliminated these effects of Cordycepin. Cordycepin may activate the P53-P21 pathway to inhibit abnormal proliferation and migration of PASMC and promote apoptosis, offering a potential approach for PAH treatment.


Subject(s)
Apoptosis , Cell Proliferation , Deoxyadenosines , Pulmonary Arterial Hypertension , Animals , Deoxyadenosines/pharmacology , Deoxyadenosines/therapeutic use , Rats , Male , Apoptosis/drug effects , Pulmonary Arterial Hypertension/drug therapy , Pulmonary Arterial Hypertension/metabolism , Pulmonary Arterial Hypertension/pathology , Cell Proliferation/drug effects , Transcriptome/drug effects , Metabolomics , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/drug effects , Monocrotaline , Pulmonary Artery/drug effects , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Rats, Sprague-Dawley , Disease Models, Animal , Vascular Remodeling/drug effects , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Linoleic Acid/pharmacology , Hypertrophy, Right Ventricular/drug therapy , Hypertrophy, Right Ventricular/metabolism , Gene Expression Profiling
13.
Chin Med ; 19(1): 75, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816815

ABSTRACT

BACKGROUND: Myocardial infarction (MI) poses a global public health challenge, often associated with elevated mortality rates and a grim prognosis. A crucial aspect of the inflammatory injury and healing process post-MI involves the dynamic differentiation of macrophages. A promising strategy to alleviate myocardial damage after MI is by modulating the inflammatory response and orchestrating the shift from pro-inflammatory (M1) to anti-inflammatory (M2) macrophages, aiming to achieve a reduced M1/M2 ratio. Nuanxinkang (NXK), a simplified herbal decoction, has demonstrated noteworthy cardioprotective, inflammation-regulating, and myocardial energy metabolism-regulating properties. METHODS: In this study, we constructed an MI model by ligating coronary arteries to investigate the efficacy of NXK in improving ventricular remodeling and cardiac function. Mice were administered NXK (1.65 g/kg/d) or an equivalent volume of regular saline via gavage for 28 consecutive days, commencing the day after surgery. Then, we conducted echocardiography to assess the cardiac function, Masson staining to illustrate the extent of myocardial fibrosis, TUNEL staining to reveal myocardial apoptosis, and flow cytometry to analyze the polarization of M1 and M2 macrophages in the hearts. Besides, a lipopolysaccharide (LPS)-induced pro-inflammatory macrophage (M1) polarization model was implemented in RAW264.7 cells to elucidate the underlying mechanism of NXK in regulating macrophage polarization. RAW264.7 cells were pre-treated with or without NXK-containing serum. Oxidative stress was detected by MitoSox staining, followed by Seahorse energy metabolism assay to evaluate alterations in mitochondrial metabolic patterns and ATP production. Both In vivo and in vitro, HIF-1α and PDK1 were detected by fluorescent quantitative PCR and Western blotting. RESULTS: In vivo, MI mice exhibited a decline in cardiac function, adverse ventricular remodeling, and an increase in glycolysis, coupled with M1-dominant polarization mediated by the HIF-1α/PDK1 axis. Notably, robust responses were evident with high-dose NXK treatment (1.65 g/kg/day), leading to a significant enhancement in cardiac function, inhibition of cardiac remodeling, and partial suppression of macrophage glycolysis and the inflammatory phenotype in MI mice. This effect was achieved through the modulation of the HIF-1α/PDK1 axis. In vitro, elevated levels of mitochondrial ROS production and glycolysis were observed in LPS-induced macrophages. Conversely, treatment with NXK notably reduced the oxidative stress damage induced by LPS and enhanced oxidative phosphorylation (OXPHOS). Furthermore, NXK demonstrated the ability to modify the energy metabolism and inflammatory characteristics of macrophages by modulating the HIF-1α/PDK1 axis. The influence of NXK on this axis was partially counteracted by the HIF-1α agonist DMOG. And NXK downregulated PDK1 expression, curtailed glycolysis, and reversed LPS-induced M1 polarization in macrophages, similar to the PDK1 inhibitor DCA. CONCLUSION: In conclusion, NXK protects against MI-induced cardiac remodeling by inducing metabolic reprogramming and phenotypic differentiation of macrophages, achieved through the modulation of the HIF-1α/PDK1 axis. This provides a novel and promising strategy for the treatment of MI.

14.
Sci Total Environ ; 939: 173595, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-38810738

ABSTRACT

Several studies have reported vapor intrusion (VI) occurring when volatile organic compound (VOC) vapors are transported through subsurface piping systems into building spaces (e.g. conduit VI). Site-specific risk assessment and risk management practices are complicated and evolving for conduit VI, especially at large hazardous waste sites, like Superfund sites, where many stakeholders are involved and have varied interests. Here, we propose a social ecological system (SES) framework as a decision-making tool to inform risk mitigation decisions. We demonstrate the SES framework using field data associated with a Superfund site near San Francisco, California. We evaluate sewer invert elevation and groundwater elevation data, as well as pre- and post- mitigation VOC concentration data within a sewer system. Unexpectedly, the sewer located above the groundwater table was determined to be a potential source of conduit VI risks. The SES framework describes how typical stakeholders associated with the site can affect and be affected by mitigation activities. It informs decisions about mitigation implementation and long-term operation efficacy by considering stakeholder roles and interests. Ultimately, gas siphons were selected as the mitigation technology for the example site. To date, approximately 6 gas siphons have been installed to mitigate conduit VI risks throughout the community. Collectively, our findings advance risk management decisions and highlight key considerations for risk mitigation approaches at hazardous waste sites, including Superfund sites, especially where VI risks are a concern.

15.
Tzu Chi Med J ; 36(2): 188-194, 2024.
Article in English | MEDLINE | ID: mdl-38645787

ABSTRACT

Objective: Although pulmonary rehabilitation and regular exercise have improved negative emotions and cognitive capacity within cases of chronic obstructive pulmonary disease (COPD), influence by exercise training upon different cognitive and memory functions in COPD is still controversial. This investigation aimed to assess whether cognitive performance and mental health are affected by the benefits of exercise training within cases of COPD. Materials and Methods: This pilot investigation included thirty-three patients with Global Initiative for Chronic Obstructive Lung Disease stage ≥B. Based on the subjects' rights, all included patients could choose to join either the exercise group or the control group, according to their free will. Twelve patients were assigned to receive exercise treatment over a 2-month period, while the remaining 16 patients were assigned to the control group. Cognitive capacity outcomes were measured using the Wechsler Memory Scale-III Word List Test, Stroop task, and psychomotor vigilance task (PVT). Mood states were assessed through the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Results: Most cases demonstrated major improvement for BDI and BAI scorings post-60-day therapy. During PVT, the omission rate decreased, while the hit rate increased, indicating an improvement in attention performance. Furthermore, this investigation found a significant increase in immediate verbal and recognition memory for word-list test. However, no major performance shifts were found on Stroop analysis. Conclusion: This investigation demonstrated that a 2-month exercise training program resulted in significant improvement in negative emotions, immediate memory, recognition memory, and attention.

16.
Electrochem Energ Rev ; 7(1): 14, 2024.
Article in English | MEDLINE | ID: mdl-38586610

ABSTRACT

Developing electrochemical energy storage and conversion devices (e.g., water splitting, regenerative fuel cells and rechargeable metal-air batteries) driven by intermittent renewable energy sources holds a great potential to facilitate global energy transition and alleviate the associated environmental issues. However, the involved kinetically sluggish oxygen evolution reaction (OER) severely limits the entire reaction efficiency, thus designing high-performance materials toward efficient OER is of prime significance to remove this obstacle. Among various materials, cost-effective perovskite oxides have drawn particular attention due to their desirable catalytic activity, excellent stability and large reserves. To date, substantial efforts have been dedicated with varying degrees of success to promoting OER on perovskite oxides, which have generated multiple reviews from various perspectives, e.g., electronic structure modulation and heteroatom doping and various applications. Nonetheless, the reviews that comprehensively and systematically focus on the latest intellectual design strategies of perovskite oxides toward efficient OER are quite limited. To bridge the gap, this review thus emphatically concentrates on this very topic with broader coverages, more comparative discussions and deeper insights into the synthetic modulation, doping, surface engineering, structure mutation and hybrids. More specifically, this review elucidates, in details, the underlying causality between the being-tuned physiochemical properties [e.g., electronic structure, metal-oxygen (M-O) bonding configuration, adsorption capacity of oxygenated species and electrical conductivity] of the intellectually designed perovskite oxides and the resulting OER performances, coupled with perspectives and potential challenges on future research. It is our sincere hope for this review to provide the scientific community with more insights for developing advanced perovskite oxides with high OER catalytic efficiency and further stimulate more exciting applications.

17.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1406-1414, 2024 Mar.
Article in Chinese | MEDLINE | ID: mdl-38621989

ABSTRACT

The clinical data of coronary heart disease(CHD) patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to March 2023 were retrospectively collected. This study involved the descriptive analysis of demographic characteristics, clinical symptoms, and tongue and pulse features. The χ~2 test was conducted to analyze the distribution of syndrome elements and their combinations at diffe-rent stages of CHD, so as to reveal the clinical characteristics and syndrome patterns at various pathological stages of CHD. This study extracted 28 symptom entries, 10 tongue manifestation entries, and 7 pulse manifestation entries, summarized the 5 main disease locations of the heart, lung, liver, spleen, and kidney, and the 8 main disease natures of blood stasis, phlegm turbidity, Qi stagnation, heat(fire), fluid retention, Qi deficiency, Yin deficiency, and Yang deficiency and 8 combinations of disease natures. The χ~2 test showed significant differences in the distribution of syndrome elements including the lung, liver, spleen, kidney, blood stasis, heat(fire), Qi stagnation, heat syndrome, water retention, Qi deficiency, Yin deficiency, and Yang deficiency between different disease stages. Specifically, the liver, blood stasis, heat(fire), and Qi stagnation accounted for the highest proportion during unstable stage, and the lung, spleen, kidney, water retention, Qi deficiency, Yin deficiency, and Yang deficiency accounted for the highest proportion at the end stage. The distribution of Qi deficiency varied in the different time periods after percutaneous coronary intervention(PCI). As shown by the χ~2 test of the syndrome elements combination, the distribution of single disease location, multiple disease locations, single disease nature, double disease natures, multiple natures, excess syndrome, and mixture of deficiency and excess varied significantly at different stages of CHD. Specifically, single disease location, single disease nature, and excess syndrome accounted for the highest proportion during the stable stage, and double disease natures accounted for the highest proportion during the unstable stage. Multiple disease locations, multiple disease natures, and mixture of deficiency and excess accounted for the highest proportion during the end stage. In conclusion, phlegm turbidity and blood stasis were equally serious during the stable stage, and a pathological mechanism caused by blood stasis and toxin existed during the unstable stage. The overall Qi deficiency worsened after PCI, and the end stage was accompanied by the Yin and Yang damage and the aggravation of water retention. There were significant differences in the distribution of clinical characteristics and syndrome elements at different stages of CHD. The pathological process of CHD witnessed the growth and decline of deficiency and excess and the combination of phlegm turbidity and blood stasis, which constituted the basic pathogenesis.


Subject(s)
Coronary Disease , Heart Failure , Percutaneous Coronary Intervention , Humans , Medicine, Chinese Traditional , Yang Deficiency , Yin Deficiency , Cross-Sectional Studies , Retrospective Studies , Coronary Disease/diagnosis , Coronary Disease/epidemiology , Syndrome , Water
18.
EMBO Mol Med ; 16(5): 1091-1114, 2024 May.
Article in English | MEDLINE | ID: mdl-38589651

ABSTRACT

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.


Subject(s)
Charcot-Marie-Tooth Disease , Mutation, Missense , Animals , Humans , Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/pathology , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Drosophila/genetics , Peripheral Nervous System Diseases/genetics , Peripheral Nervous System Diseases/pathology , Disease Models, Animal , Tubulin/genetics , Tubulin/metabolism , Nuclear Proteins , Adaptor Proteins, Signal Transducing
19.
Huan Jing Ke Xue ; 45(3): 1830-1839, 2024 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-38471894

ABSTRACT

The removal mechanisms of phthalic acid esters (PAEs) have attracted much attention because of their endocrine-disrupting properties and persistence in environmental media. In order to reveal the removal mechanism of PAEs and involved keystone taxa and functional genes, purple soils were polluted by di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP), respectively, along a gradient of 0, 5, 10, and 20 mg·kg-1 and cultured for 90 days in the dark. The results showed that the degradation dynamics of DBP and DEHP were well-fitted by the first-order kinetic model, and the half-life of DBP and DEHP ranged from 17.0 to 38.2 days. The degradation rate of DBP (5 mg·kg-1) was the fastest, and that of DEHP (20 mg·kg-1) was the slowest. The soil samples of the seventh day and the fifteenth day were analyzed using metagenomic sequencing. NMDS and cluster analysis showed that there was a significant difference between the bacterial community structure of soil samples from the seventh day and the fifteenth day. The relative abundance of Actinobacteria increased from the seventh day to the fifteenth day. The smaller the half-life of DBP or DEHP, the higher the relative abundance of Actinobacteria in the different treatments. In addition, Streptomyces was the dominant genus in all polluted soils. Co-occurrence network analysis elucidated that Pandoraea was a keystone genus of the soil bacterial communities, which could be used to indicate the pollution levels of DBP and DEHP. The results of KEGG annotation demonstrated that Pandoraea was responsible for benzoate degradation, quorum sensing, ABC transporters, and the two-component system and could promote the intercellular communications and the microbial growth and proliferation and maintain the stability of the community structure. Therefore, the degradation rate of DBP and DEHP in purple soils depended on their initial content and their own properties. Actinobacteria played an important role in the PAEs degradation, and Pandoraea played a major part in promoting PAEs degradation and regulating the stability of the structure and function of degrading bacterial communities.


Subject(s)
Diethylhexyl Phthalate , Phthalic Acids , Soil/chemistry , Phthalic Acids/analysis , Dibutyl Phthalate , Esters/analysis
20.
J Thorac Dis ; 16(1): 51-64, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38410615

ABSTRACT

Background: Transthoracic echocardiography (TTE) is recommended as the most important noninvasive screening tool for the diagnosis of pulmonary hypertension (PH), sonographers usually measure the volume of regurgitant flow rather than evaluating the spectral quality, so physicians will determine whether the ultrasound measurements of pulmonary arterial systolic pressure (US-PASP) are reliable based on the volume of tricuspid regurgitation (TR). Therefore, for the first time, we grade the quality of TR spectrum (TRS) based on its integrity and clarity, aiming to assess clinical application value of different tricuspid regurgitant spectrum quality grades (TR-SQG), and investigate whether the accuracy of US-PASP is more trustworthy than TR. Methods: We retrospectively analyzed 108 patients with chronic thromboembolic PH (CTEPH) to compare the correlation and agreement between US-PASP and right heart catheterization measurements of PASP (RHC-PASP). TR area (TRA) and TRS were measured in each patient, and TR-SQG was performed. Results: The correlation coefficients between US-PASP and RHC-PASP were r=0.622 (P<0.001), r=0.754 (P<0.001), r=0.595 (P<0.001) in mild, moderate, severe TR, and r=0.301 (P=0.135), r=0.747 (P<0.001), r=0.739 (P<0.001), r=0.828 (P<0.001) in TR-SQG I-IV, respectively. Bland-Altman analysis revealed the mean biases of 5.05, 3.06, 7.62 mmHg in mild, moderate, severe TR, and -16.47, -8.07, 1.82, 6.09 mmHg in TR-SQG I-IV, respectively. In mild TR with the TR-SQG III and IV, the correlation coefficients between US-PASP and RHC-PASP were r=0.779 (P<0.001), intraclass correlation coefficient (ICC) =0.774, paired t-test P=0.160, respectively; and the consistency was significantly higher than that of mild TR without considering TR-SQG. In moderate TR with the TR-SQG III and IV, the r=0.749, ICC =0.746, paired t-test P=0.298 between US-PASP and RHC-PASP. Conclusions: The US-PASP with TR-SQG III or IV is trustworthy, and its accuracy and consistency are better than those predicted by the traditional severity of TR. The establishment of the ultrasound evaluation system of TR-SQG helps clinicians to judge whether the US-PASP is accurate, credible, and reliable.

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