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1.
J Environ Sci (China) ; 149: 35-45, 2025 Mar.
Article in English | MEDLINE | ID: mdl-39181648

ABSTRACT

Post-etching method using dilute acid solutions is an effective technology to modulate the surface compositions of metal-oxide catalysts. Here the α-MnO2 catalyst treated with 0.1 mol/L nitric acid exhibits higher ozone decomposition activity at high relative humidity than the counterpart treated with acetic acid. Besides the increases in surface area and lattice dislocation, the improved activity can be due to relatively higher Mn valence on the surface and newly-formed Brønsted acid sites adjacent to oxygen vacancies. The remnant nitro species deposited on the catalyst by nitric acid treatment is ideal hydrophobic groups at ambient conditions. The decomposition route is also proposed based on the DRIFTS and DFT calculations: ozone is facile to adsorb on the oxygen vacancy, and the protonic H of Brønsted acid sites bonds to the terminal oxygen of ozone to accelerate its cleavage to O2, reducing the reaction energy barrier of O2 desorption.


Subject(s)
Humidity , Manganese Compounds , Oxides , Ozone , Ozone/chemistry , Oxides/chemistry , Manganese Compounds/chemistry , Catalysis , Models, Chemical
2.
Nat Commun ; 15(1): 8748, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39384788

ABSTRACT

Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. ß-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that ß-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated ß-synuclein mutations lose these capacities. Exogenous ß-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated ß-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/ß-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and ß-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.


Subject(s)
Amyloid , Caenorhabditis elegans , Parkinson Disease , Phase Transition , alpha-Synuclein , beta-Synuclein , alpha-Synuclein/metabolism , alpha-Synuclein/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/genetics , Animals , Humans , beta-Synuclein/metabolism , beta-Synuclein/genetics , Parkinson Disease/metabolism , Parkinson Disease/genetics , Amyloid/metabolism , Mutation , Lewy Body Disease/metabolism , Lewy Body Disease/genetics , Lewy Body Disease/pathology , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Presynaptic Terminals/metabolism , Longevity/genetics
3.
Exp Biol Med (Maywood) ; 249: 10155, 2024.
Article in English | MEDLINE | ID: mdl-39376717

ABSTRACT

Tumor immune microenvironment is crucial for diffuse large B-cell lymphoma (DLBCL) development. However, the mechanisms by which super-enhancers (SEs) regulate the interactions between DLBCL cells and tumor-infiltrating immune cells remains largely unknown. This study aimed to investigate the role of SE-controlled genes in regulating the interactions between DLBCL cells and tumor-infiltrating immune cells. Single-cell RNA-seq, bulk RNA-seq and H3K27ac ChIP-seq data were downloaded from the Heidelberg Open Research Data database and Gene Expression Omnibus database. HOMER algorithm and Seurat package in R were used for bioinformatics analysis. Cell proliferation and lactate dehydrogenase (LDH) release was detected by MTS and LDH release assays, respectively. Interaction between B cell cluster and CD8+ T cell and NK cell cluster was most obviously enhanced in DLBCL, with CD70-CD27, MIF-CD74/CXCR2 complex, MIF-CD74/CD44 complex and CCL3-CCR5 interactions were significantly increased. NK cell sub-cluster showed the strongest interaction with B cell cluster. ZZZ3 upregulated the transcription of CD70 by binding to its SE. Silencing CD70 in DOHH2 cells significantly promoted the proliferation of co-cultured NK92 cells and LDH release from DOHH2 cells, which was counteracted by ZZZ3 overexpression in DOHH2 cells. CD70 silencing combined with PD-L1 blockade promoted LDH release from DOHH2 cells co-cultured with NK92 cells. In conclusion, DLBCL cells inhibited the proliferation and killing of infiltrating NK cells by regulating ZZZ3/CD70 axis. Targeting ZZZ3/CD70 axis combined with PD-L1 blockade is expected to be a promising strategy for DLBCL treatment.


Subject(s)
CD27 Ligand , Killer Cells, Natural , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/genetics , Humans , Killer Cells, Natural/metabolism , Killer Cells, Natural/immunology , CD27 Ligand/metabolism , CD27 Ligand/genetics , Cell Line, Tumor , Tumor Microenvironment , Gene Expression Regulation, Neoplastic , Cell Proliferation , Multiomics
4.
J Integr Med ; 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39358063

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear. OBJECTIVES: To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was designed as a multicenter, assessor-blind, randomized controlled trial. Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group. The treatment group received individualized TCM non-drug measures in combination with prone position ventilation, while the control group received prone position ventilation only for 5 consecutive days. MAIN OUTCOME MEASURES: The primary outcome measures were the percentage of patients with improved oxygen saturation (SpO2) at the end of the 5-day intervention, as well as changes of patients' respiratory rates. The secondary outcome measures included changes in SpO2 and total score on the self-made respiratory symptom scale. The improvement rate, defined as a 3-day consecutive increase in SpO2, the duration of prone positioning, and adverse events were recorded as well. RESULTS: Among the 198 patients included in the intention-to-treat analysis, 159 (80.3%) completed all assessments on day 5, and 39 (19.7%) patients withdrew from the study. At the end of the intervention, 71 (91%) patients in the treatment group had SpO2 above 93%, while 61 (75.3%) in the control group reached this level. The proportion of participant with improved SpO2 was significantly greater in the intervention group (mean difference [MD] = 15.7; 95% confidence interval [CI]: 4.4, 27.1; P = 0.008). Compared to the baseline, with daily treatment there were significant daily decreases in respiratory rates in both groups, but no statistical differences between groups were found (all P ≥ 0.05). Compared to the control group, the respiratory-related symptoms score was lower among patients in the treatment group (MD = -1.7; 95%CI: -2.8, -0.5; P = 0.008) after day 3 of treatment. A gradual decrease in the total scores of both groups was also observed. Thirty-one adverse events occurred during the intervention, and 2 patients were transferred to the intensive care unit due to deterioration of their illness. CONCLUSION: TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19. The combined therapy significantly increased SpO2 and improved symptom scores compared to prone positioning alone, thus improving the patients' respiratory function to help them recover. However, the improvement rate did not differ between the two groups. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300068319). Please cite this article as: Yin X, Jin Z, Li F, Huang L, Hu YM, Zhu BC, Wang ZQ, Li XY, Li JP, Lao LX, Mi YQ, Xu SF. Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial. J Integr Med. 2024; Epub ahead of print.

5.
Plant Physiol Biochem ; 216: 109178, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39388752

ABSTRACT

Cadmium (Cd), as a heavy metal pollutant, can seriously affect plant growth and development. Boron (B), as an indispensable nutrient element, plays an important role in plant growth and cell wall (CW) synthesis. However, the physiological effects of B and Cd on plant growth and the mechanism of Cd chelation by the CW remain unclear. Here, we investigate the effect of exogenous B on Cd accumulation in CW components of Cosmos bipinnatus roots and its mechanism of Cd mitigation. Under B deficiency and single Cd (30 µM) treatments, the growth of C. bipinnatus was significantly inhibited, but the addition of exogenous B significantly increased plant biomass, which increased the Cd content in the underground parts of C. bipinnatus by 20.18% and reduced the Cd translocation factor by 22.22%. Meanwhile, application of exogenous B affected the subcellular Cd content across various Cd forms and alleviated Cd-induced oxidative stress in C. bipinnatus. Additionally, exogenous B and Cd and their mixtures affected the functional groups of the root CW, the proportion of polysaccharide components, the Cd content of polysaccharides, and the polysaccharide uronic acid content of C. bipinnatus. However, B application increased 3-deoxy-oct-2-ulosonic acid content, pectin esterase activity, low esterified pectin content, and its Cd content by 149.52%, 55.69%, 206.38%, and 150.02%, respectively, compared to Cd treatment alone. Thus, our study showed that B mitigates the toxicity of Cd to plants, revealing the effect of B on the physiological aspects of Cd tolerance in plants.

6.
J Adolesc ; 2024 Oct 11.
Article in English | MEDLINE | ID: mdl-39392218

ABSTRACT

INTRODUCTION: Bullying among adolescents is a global public health issue prevalent in schools, posing significant risks to positive adolescent development. Studies have shown that bullied adolescents tend to engage in more bullying perpetration, but this underlying process of longitudinal correlation has not been fully elucidated. METHODS: Based on two waves of longitudinal data collected from 347 junior and 144 senior high school students in China (Mage = 13.66 years, SDage = 1.46, 59.27% boys) at 1-year intervals, two moderated chain-mediation models were used to explore the longitudinal correlations between bullying victimization and bullying perpetration and its underlying processes. RESULTS: The results found a significant positive correlation between adolescents' bullying victimization experiences 1 year prior and bullying perpetration 1 year later. Furthermore, fear of negative evaluation and psychache played a longitudinal chain-mediating role in the process, with self-esteem and grade moderating this mediating pathway, either enhancing or weakening the effect. CONCLUSIONS: This study demonstrates that prior bullying victimization is longitudinally and positively associated with subsequent bullying perpetration among adolescents. This process is mediated by fear of negative evaluation and psychache, with self-esteem and grade level as moderators. Based on these conclusions, we have formulated the Threat-Motivation Model, offering a framework to understand the relationship between bullying victimization and bullying perpetration. Practical implications, including strategies to reduce bullying in youth groups, are discussed.

7.
Infect Dis (Lond) ; : 1-11, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264585

ABSTRACT

OBJECTIVE: Accurate and rapid identification of causative pathogens is essential to guide the clinical management of lower respiratory tract infections (LRTIs). Here we conducted a single-centre prospective study in 284 patients suspected of lower respiratory tract infections to evaluate the utility of a nucleic acid test based on highly multiplexed polymerase chain reaction (PCR) and CRISPR-Cas12a. METHODS: We determined the analytical and diagnostic performance of the CRISPR assay using a combination of reference standards, including conventional microbiological tests (CMTs), metagenomic Next-Generation Sequencing (mNGS), and clinical adjudication by a panel of experts on infectious diseases and microbiology. RESULTS: The CRISPR assay showed a higher detection rate (63.0%) than conventional microbiological tests (38.4%) and was lower than metagenomic Next-Generation Sequencing (72.9%). In detecting polymicrobial infections, the positivity rate of the CRISPR assay (19.4%) was higher than conventional microbiological tests (3.5%) and lower than metagenomic Next-Generation Sequencing (28.9%). The overall diagnostic sensitivity of the CRISPR assay (67.8%) was higher than conventional microbiological tests (41.8%), and lower than metagenomic Next-Generation Sequencing (93.2%). CONCLUSIONS: Considering the low cost, ease of operation, short turnaround time, and broad range of pathogens detected in a single test, the CRISPR assay has the potential to be implemented as a screening tool for the aetiological diagnosis of lower respiratory tract infections patients, especially in cases where atypical bacteria or coinfections are suspected.

8.
Biomed Pharmacother ; 179: 117387, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39245002

ABSTRACT

As the global population ages, the incidence of Parkinson's Disease (PD) continues to rise, imposing significant social and economic burdens. Mangiferin (MGF), a polyphenolic, bioactive compound has been shown to play a role in the prevention and treatment of PD. This study investigates the neuroprotective effects of MGF in an MPTP-induced zebrafish model of PD through transcriptome analysis. Initially, optimal concentrations for modeling were determined using various MPTP and MGF combinations. The zebrafish were then divided into control, MPTP-treated, and MGF co-treated groups. Subsequent evaluations included hatching rates, mortality rates, growth and development conditions, spontaneous motor abilities, as well as measurements of enzymatic activities of SOD, CAT, and levels of GSH. Ultimately, the therapeutic efficacy of MGF on the PD model in zebrafish was assessed through transcriptome sequencing. The results demonstrated that MPTP treatment induced PD-associated symptoms in zebrafish, while MGF treatment significantly improved the motor abilities and survival rates of the PD model zebrafish, effectively reducing oxidative stress and ameliorating PD symptoms. Transcriptome sequencing further revealed that MGF may mitigate mitochondrial-related oxidative stress in PD zebrafish by modulating the expression of critical genes including lrrk2, vps35, atp13a, dnajc6, and uchl1. Differential gene expression analysis indicated that these genes are primarily involved in vital signaling pathways, such as neuroactive ligand-receptor interaction, and the calcium signaling pathway. In summary, our study provides robust scientific evidence supporting MGF as a potential therapeutic candidate for PD by preserving mitochondrial homeostasis and elucidating its mechanisms of action.


Subject(s)
Gene Expression Profiling , Oxidative Stress , Xanthones , Zebrafish , Animals , Xanthones/pharmacology , Gene Expression Profiling/methods , Oxidative Stress/drug effects , Neuroprotective Agents/pharmacology , Disease Models, Animal , Transcriptome/drug effects , Parkinson Disease/drug therapy , Parkinson Disease/genetics , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Antiparkinson Agents/pharmacology , Male
9.
Int Immunopharmacol ; 142(Pt B): 113221, 2024 Dec 05.
Article in English | MEDLINE | ID: mdl-39321709

ABSTRACT

Programmed cell death ligand 1 (PDL1) has been implicated in immune evasion in various tumor types. The objective of this investigation was to assess the correlation between metastasis-associated interferon-induced transmembrane protein 2 (IFITM2) and PDL1, and explore their impact on tumor immunity in gastric cancer (GC). The expression of IFITM2 and PDL1 in human GC tissues was initially evaluated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, as well as immunohistochemistry (IHC). Subsequently, the relationship between IFITM2 and PDL1 was analyzed through Real-time quantitative PCR (RT-qPCR) and western blotting after cell transfection and inhibitor treatment in vitro. The role of IFITM2 and PDL1 in immune killing was further elucidated in both in vitro and in vivo settings. Our study revealed frequent overexpression of IFITM2 and PDL1 in GC. Notably, IFITM2 expression was significantly associated with lymphatic metastasis, clinical stage, and poor survival. Moreover, a positive correlation between PDL1 expression and IFITM2 expression in GC was identified. The activation of tumor-derived IFITM2 was found to enhance PDL1 expression via the JAK/STAT3 pathway in human GC cells (MKN28 and MKN45), leading to apoptosis of Jurkat T cells. Furthermore, IFITM2 induced PDL1 expression in a xenograft mouse model of GC. Based on our findings, we propose that IFITM2 modulates PDL1 expression and tumor immunity through the JAK/STAT3 pathway in GC cells, highlighting the potential of IFITM2 as a therapeutic target for GC immunotherapy.


Subject(s)
B7-H1 Antigen , Janus Kinases , Membrane Proteins , STAT3 Transcription Factor , Signal Transduction , Stomach Neoplasms , Humans , Stomach Neoplasms/immunology , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/metabolism , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , STAT3 Transcription Factor/metabolism , Animals , Cell Line, Tumor , Janus Kinases/metabolism , Female , Membrane Proteins/metabolism , Membrane Proteins/genetics , Male , Mice , Gene Expression Regulation, Neoplastic , Middle Aged , Mice, Nude , Mice, Inbred BALB C
10.
Heart Rhythm ; 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39288882

ABSTRACT

BACKGROUND: New-onset permanent pacemaker implantation (PPMI) is still a common complication after transcatheter aortic valve implantation (TAVI) with adverse clinical outcomes. OBJECTIVE: The purpose of this study was to investigate whether left bundle branch area pacing (LBBAP) improves long-term clinical results compared with traditional right ventricular pacing (RVP) in patients requiring PPMI after TAVI. METHODS: A total of 237 consecutive patients undergoing RVP (N = 117) or LBBAP (N = 120) after TAVI were retrospectively included. Long-term outcomes, including all-cause death, heart failure rehospitalization (HFH), and left ventricular ejection fraction (LVEF) change compared to baseline, were obtained until 5 years post-TAVI. RESULTS: The mean age of the overall population was 74 years, with a mean surgical risk score of 4.4%. The paced QRS duration was significantly longer in the RVP group compared with the LBBAP group (151 ± 18 vs 122 ± 12 ms; P < .001). No difference was found between the 2 groups in all-cause death (13.7% vs 13.3%; adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.37-1.58; P = .466) or the composite endpoint of death and HFH (29.9% vs 19.2%; adjusted HR, 1.22; 95% CI, 0.70-2.13; P = .476); however, the risk of HFH was significantly higher in the RVP group at 5 years after TAVI (21.4% vs 7.5%; adjusted HR, 2.26; 95% CI, 1.01-5.08; P = .048). There was greater improvement of LVEF over time in the LBBAP group (P = .046 for LVEF changes over time between groups). CONCLUSIONS: LBBAP improved long-term clinical outcomes compared with RVP in patients undergoing PPMI after TAVI in terms of less HFH and better LVEF improvement.

11.
Biosens Bioelectron ; 267: 116716, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39316867

ABSTRACT

Accurately differentiating respiratory diseases caused by viruses is challenging because of the similarity in their early or clinical symptoms. Moreover, different infection sources require different treatments. However, the current diagnostic methods have limited differentiating efficiency and sensitivity. We developed a dual-system immunosensor with a bilayer fluorescent label as a signal amplifier for the on-site, sensitive, and accurate identification of multiple respiratory viruses (RVs). The nanomaterial, comprising a polystyrene (PS) nanosphere core encapsulated by two layers of CdSe@ZnS-COOH quantum dots (QDs), outperforms the conventional color and fluorescent labels in RV detection. The dual-system detection platform, comprising a PS@DQD-based lateral flow immunoassay (LFIA) and a PS@DQD-based homogeneous sensor, enables qualitative and quantitative screening of multiple respiratory viruses within 10 and 30 min, respectively, depending on the specific detection requirements for different application scenarios. This remarkable method provides 51.2 to 1000 times sensitivity improvement over commercial antigen detection kits and greater than 12.5 to 100 times improvement over QD-based immunosensors. Furthermore, we comprehensively evaluated the specificity, reproducibility, and stability of the integrated dual-system detection platform, demonstrating its reliability. Remarkably, the respiratory viral testing was validated using biological samples, thus illustrating its promise and convenience in the detection of respiratory viruses.

12.
Zhongguo Zhen Jiu ; 44(9): 1017-22, 2024 Sep 12.
Article in Chinese | MEDLINE | ID: mdl-39318292

ABSTRACT

OBJECTIVE: To compare the improvement of joint function in female patients with early-middle-stage knee osteoarthritis (KOA) treated by oblique insertion at ashi point with long needle and oral celecoxib capsule. METHODS: A total of 105 female patients with early-middle-stage KOA were randomly divided into an observation group (65 cases, 6 cases dropped out, 3 cases were discontinued) and a control group (40 cases, 6 cases dropped out, 2 cases were discontinued). Patients in the observation group were treated with oblique insertion at ashi point (hard knots of quadriceps femoris, hamstring muscle, popliteal muscle, etc.) with long needle, once every other 3 days, twice a week, for a total of 2 weeks. Patients in the control group were treated with oral celecoxib capsules, 0.2 g each time, once a day for 2 weeks. Both groups started functional exercise after 2 weeks of treatment. The joint function score of Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and pain visual analogue scale (VAS) score of the two groups were observed before and after treatment and after 6 weeks of treatment completion (follow-up), the 12-item short-form health survey (SF-12) score was compared between the two groups before treatment and in follow-up, and the safety of the two groups was evaluated. RESULTS: After treatment and during the follow-up, the joint function scores of WOMAC and VAS scores of the two groups were lower than those before treatment (P<0.05). During the follow-up, the joint function scores of WOMAC and VAS scores were lower than those after treatment (P<0.05), and the SF-12 scores were higher than those before treatment (P<0.05) in the two groups. After treatment, the joint function score of WOMAC of the observation group was lower and the VAS score was higher than those of the control group (P<0.001, P<0.01). During the follow-up, the SF-12 score of the observation group was higher than that of the control group (P<0.05). No serious adverse reactions occurred in both groups. CONCLUSION: The treatment of oblique insertion at ashi point with long needle can improve the knee joint function and quality of life of female patients with early-middle-staqe KOA, which is better than oral celecoxib capsule.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Osteoarthritis, Knee , Humans , Female , Osteoarthritis, Knee/physiopathology , Osteoarthritis, Knee/drug therapy , Osteoarthritis, Knee/therapy , Middle Aged , Aged , Knee Joint/physiopathology , Treatment Outcome , Adult , Needles
13.
Ecotoxicol Environ Saf ; 285: 117031, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39341137

ABSTRACT

The toxicity mechanisms of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q), an antioxidant derivative of 6PPD via ozone reaction commonly used in rubber and tire industries, were investigated in zebrafish larvae with concentrations ranging from 0 to 50 µg/L. Despite normal hatchability, 6PPD-Q exposure led to reduced body length and swimming distance in 120 hours post-fertilization (hpf) larvae. At the highest concentration (50 µg/L), 6PPD-Q significantly impaired dopaminergic neuron development and neurotransmitter levels, including dopamine, 5-hydroxytryptamine, and glutamate. Transcriptome profiling unveiled perturbations in growth and developmental gene expression, such as upregulation of runx2a, runx2b, and ghrl (ghrelin and obestatin prepropeptide), and downregulation of stat1b, auto1, and cidea. Notably, anamorelin, a growth hormone secretagogue receptor (GHSR) agonist, recovered the behavioral deficits induced by 6PPD-Q, implying a neuroprotective role of ghrelin possibly mediated via the ghrelin/GHSR pathway. Collectively, our findings indicate that ghrelin upregulation may counteract 6PPD-Q toxicity in zebrafish larvae, shedding light on potential therapeutic avenues for mitigating the adverse effects of this antioxidant byproduct.

14.
Heliyon ; 10(18): e36397, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39347412

ABSTRACT

Purpose: Liver-expressed antimicrobial peptide-2 (LEAP2) is identified as an endogenous antagonist and inverse agonist of the growth hormone secretagogue receptor type 1a (GHSR1a), its effect on the GHSR1a is contrary to the role of GHRELIN. Growth hormone (GH) is a crucial hormone for early development. Previous studies report that LEAP2 dose-dependently attenuates ghrelin-induced GH secretion, and Leap2-knockout mice exhibit increased plasma GH levels after GHRELIN administration. Clinical data revealed a possible correlation between LEAP2 and height development. However, the role of LEAP2 in early development remains unclear. This study aimed to investigate the role of LEAP2 in early development using leap2 mutant zebrafish larvae as a model. Method: We analyzed the conservation of LEAP2 peptide across multiple species and generated leap2 mutants in zebrafish by CRISPR-Cas9, dynamically observed and measured the growth and development of zebrafish larvae from fertilization to 5 day post fertilization (dpf). In situ hybridization, transcriptome sequencing, quantitative real-time PCR and Western blot were used to detect the expression levels of GH and its signaling in early stage of embryonic development. Result: Our data demonstrate that zebrafish with a knockout of the leap2 gene display a significant increase in hatching rate, body length, and the distance between their eyes, all without visible developmental defects in the early stages of development. In addition, both RNA and protein analyses revealed a significant increase in GH expression in leap2 mutant. Conclusion: In general, this study demonstrates that LEAP2 regulates the expression of GH during early development, particularly influencing body length.

15.
Biomimetics (Basel) ; 9(9)2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39329594

ABSTRACT

Feature selection (FS) is a classic and challenging optimization task in most machine learning and data mining projects. Recently, researchers have attempted to develop more effective methods by using metaheuristic methods in FS. To increase population diversity and further improve the effectiveness of the beluga whale optimization (BWO) algorithm, in this paper, we propose a multi-strategies improved BWO (MSBWO), which incorporates improved circle mapping and dynamic opposition-based learning (ICMDOBL) population initialization as well as elite pool (EP), step-adaptive Lévy flight and spiral updating position (SLFSUP), and golden sine algorithm (Gold-SA) strategies. Among them, ICMDOBL contributes to increasing the diversity during the search process and reducing the risk of falling into local optima. The EP technique also enhances the algorithm's ability to escape from local optima. The SLFSUP, which is distinguished from the original BWO, aims to increase the rigor and accuracy of the development of local spaces. Gold-SA is introduced to improve the quality of the solutions. The hybrid performance of MSBWO was evaluated comprehensively on IEEE CEC2005 test functions, including a qualitative analysis and comparisons with other conventional methods as well as state-of-the-art (SOTA) metaheuristic approaches that were introduced in 2024. The results demonstrate that MSBWO is superior to other algorithms in terms of accuracy and maintains a better balance between exploration and exploitation. Moreover, according to the proposed continuous MSBWO, the binary MSBWO variant (BMSBWO) and other binary optimizers obtained by the mapping function were evaluated on ten UCI datasets with a random forest (RF) classifier. Consequently, BMSBWO has proven very competitive in terms of classification precision and feature reduction.

16.
Front Neurol ; 15: 1412558, 2024.
Article in English | MEDLINE | ID: mdl-39323435

ABSTRACT

The treatment time window for acute cerebral infarction in global guidelines is within 24 h. We report a patient who was admitted to the hospital and underwent endovascular treatment reaching 40 h. During vascular examination, the thrombus moved to distant segment, and then the surgeon quickly performed endovascular treatment. The patient ultimately achieved a good outcome. This case indicates that thrombus is moveable at any time, we expected to provide advice to clinical doctors that vascular examination should also be arranged as soon as possible to clarify the etiology in stroke patients especially with low NIHSS scores.

17.
Environ Pollut ; 362: 124976, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39293661

ABSTRACT

Iron-biochar composite is a promising catalyst in Fenton-like system for removal of organic pollutants. Nevertheless, low cycling rate of Fe(III)/Fe(II), high iron leaching and low H2O2 utilization efficiency impedes its application. Herein, a iron-based biochar (C-Fe) coated with tartaric acid (TA) was synthesized. The specific structure of inherent graphitized carbon and TA coating improved the removal efficiency of dibutyl phthalate (DBP) to 93%, promoted 2-fold increase in HO• production in H2O2 activation, improved the cycling rate of Fe(III)/Fe(II), and mitigated Fe leaching significantly. The developed HO• and 1O2 dominated Fenton-like system had an excellent pH universality and anti-interference to inorganic ions and real water matrixes. Moreover, C-Fe-TA has been shown to efficiently degrade DBP by using the dissolved oxygen in water to generate HO•. This work provided a novel insight for sustainable and efficient HO• and 1O2 generation, which motivated the development of new water treatment technology based on efficient iron-biochar catalyst.

19.
Electrophoresis ; 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39286940

ABSTRACT

The large surface area, excellent thermal stability and easy modification make microporous organic networks (MONs) good candidates in the field of gas chromatography (GC). Due to the limited species and highly conjugated networks of MONs, their applications are still in infancy and restricted. To accelerate their developments and to enrich their types in GC, here we report the first example of synthesizing alkyl MON and its capillary column for GC separation of position isomers. Linear 1,8-dibromooctane is used as the alkyl monomer instead of traditional aromatic ones to construct novel alkyl MON to decrease the inherent conjugated characteristic of MONs. The alkyl MON exhibits good thermal stability (up to 350°C), large surface area (1173 m2 g-1), and non-polar character, allowing good resolution for alkanes, alkyl benzenes, alcohols, ketones, and diverse position isomers, including dichlorobenzene, trichlorobenzene, bromotoluene, nitrotoluene, methylbenzaldehyde, and ionone with the limits of detection (0.003 mg mL-1) and limits of quantitation of (0.10 mg mL-1). The in situ growth-prepared alkyl MON column demonstrates remarkable duration time and precisions for the retention relative standard deviations, (RSDs%, intra-day, n = 7), 0.06%-0.53% (intra-day, n = 7), and 2.87%-10.59% (column-to-column, n = 3). In addition, the fabricated alkyl MON-coated capillary column offers better resolution than three commercial GC columns for the resolution of methylbenzaldehyde, bromotoluene, and chlorotoluene isomers. This work reveals the practicability for synthesizing alkyl MONs and demonstrates their prospects for position isomers separation.

20.
mSystems ; : e0072224, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39287378

ABSTRACT

Klebsiella pneumoniae carbapenemase (KPC) variants can contribute to resistance to ceftazidime-avibactam (CZA) in Klebsiella pneumoniae (KP). However, two-copy KPC variant-mediated resistance to CZA has rarely been reported to date. Here, we aimed to clarify the evolutionary trajectory of CZA resistance driven by mutations in double-copy blaKPC-2 to blaKPC-189 carried by the tandem core structure (ISKpn6-blaKPC-ISKpn27-tnpR-IS26) during treatment of ST11 carbapenem-resistant K. pneumoniae (CRKP). The CZA-resistant KP strain carried double-copy blaKPC-189, a variant with alanine-threonine and aspartate-tyrosine substitutions at Ambler amino acid positions 172 (A172T) and 179 (D179Y) of blaKPC-2. Clone experiments confirmed that, compared with that of the wild-type blaKPC-2 clone strain, the minimum inhibitory concentration of CZA increased 16-fold in the blaKPC-189-mutant strain. Furthermore, protein structure analysis revealed the A172T and D179Y mutations of blaKPC-189 can have a direct effect on the binding affinity of CAZ and AVI for KPC. Sequence comparison revealed that blaKPC-189 was mutated in a double-copy format upon CZA exposure, which was carried by the IS26-mediated tandem core structure ISKpn27-blaKPC-ISKpn6. This tandem core structure apparently evolves in vivo during infection, although not by self-transferring, and multiple ISKpn27-blaKPC-ISKpn6 copy numbers could mediate transferable CZA resistance upon mobilization. In addition, compared with the wild-type blaKPC-2 gene, the blaKPC-189 gene had no fitness cost. In summary, our study highlighted the emergence of CZA-resistant blaKPC-189 variants in the ST11 clone and the presence of a double-copy blaKPC-189 in the IncFII-type plasmid, which is carried by a tandem core structure (IS26-ISKpn6-blaKPC-189-ISKpn27-tnpR-IS26). IMPORTANCE: To date, ceftazidime-avibactam (CZA) resistance caused by double-copy Klebsiella pneumoniae carbapenemase (KPC) variants has not been elucidated. The multicopy forms of carbapenem resistance genes carried by the same plasmid are relatively rare in most carbapenem-resistant Enterobacteriaceae. In this study, we elucidate the evolutionary trajectory of CZA resistance in ST11 carbapenem-resistant K. pneumoniae harboring a double-copy blaKPC and provide new insights into the mechanisms of acquired resistance to CZA.

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