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1.
Sci Rep ; 14(1): 18909, 2024 08 14.
Article in English | MEDLINE | ID: mdl-39143105

ABSTRACT

In recent years, sleep problems among college students have become increasingly prominent, especially in the context of the COVID-19 pandemic, and their sleep quality has deteriorated dramatically, severely affecting their physical and mental health. Numerous research studies have investigated the relationship between mindfulness and sleep quality; however, it is still unclear what psychological process underlies this relationship. In the current study, college students' bed procrastination and self-control as mediating factors in the association between mindfulness and sleep quality were investigated. Using the convenience sampling method, 763 Chinese college students (mean age = 19.48 years, SD = 2.06) were recruited to complete self-reported questionnaires that included the Mindful Attention Awareness Scale, Self-Control Scale, Bed Procrastination Scale, and Sleep Quality Scale. All statistical analyses were performed using SPSS 23.0 software. Results showed that (a) mindfulness was positively associated with sleep quality; (b) both self-control and bed procrastination mediated the relationship between mindfulness and sleep quality, and (c) self-control and bed procrastination sequentially mediated the relationship between mindfulness and sleep quality. These findings collectively suggest a potential mechanism for how mindfulness influences sleep quality, providing a therapeutic target for mindfulness-based interventions aimed at helping college students improve sleep quality.


Subject(s)
COVID-19 , Mindfulness , Procrastination , Self-Control , Sleep Quality , Students , Humans , COVID-19/psychology , COVID-19/epidemiology , Male , Female , Students/psychology , Young Adult , Self-Control/psychology , Universities , Adolescent , Surveys and Questionnaires , Pandemics , SARS-CoV-2 , Adult , Self Report , Sleep/physiology , China/epidemiology
2.
Ther Adv Drug Saf ; 15: 20420986241266439, 2024.
Article in English | MEDLINE | ID: mdl-39086615

ABSTRACT

Background: Oxaliplatin-associated shock (referred to as shock) is a rare but life-threatening adverse event. Objectives: This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock, and assess the cycle-to-shock during oxaliplatin treatment. Design: The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Methods: All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012-2016). Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for oxaliplatin's link to shock incidence. Results: Among 6932 oxaliplatin recipients, 331 suffered shock. In all, 3309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock (adjusted OR: 2.08, 95% CI: 1.23-3.52). Two independent risk factors were male sex (adjusted OR: 1.33, 95% CI: 1.05-1.69) and heart diseases (adjusted OR: 1.65, 95% CI: 1.17-2.32). The case-crossover analysis revealed a more than fourfold risk (OR: 4.4, 95% CI: 1.67-11.62). In total, 22 of 331 shock cases were exposed to oxaliplatin within 2 days of shock onset, with a median cycle-to-shock time at the seventh cycle. Conclusion: Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and heart disease are two independent risk factors.


This pioneering study identified potential independent risk factors and the cycle-to-shock of oxaliplatin-associated shock which is a rare but life-threatening adverse event Why was the study done? Oxaliplatin-induced anaphylactic shock (referred to as shock) is a rare but life-threatening adverse event which is a harmful and undesirable experience associated with medical care in a patient. What did the researchers do? This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock and assess the cycle-to-shock during oxaliplatin treatment. All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012­2016). The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Conditional logistic regression was used to quantify the association between oxaliplatin and shock incidence. What did the researchers find? Among 6,932 oxaliplatin recipients, 331 suffered shock. 3,309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock. Independent risk factors were male sex and heart diseases. The risk of shock was 33% higher for males and 65% higher for people with heart diseases compared to females and those without heart diseases. The case-crossover analysis revealed a more than four-fold risk of shock of oxaliplatin. Twenty-two of 331 shock cases were exposed to oxaliplatin within two days before the shock onset. The median cycle-to-shock time is at the seventh cycle. What do the findings mean? Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and having heart diseases are two independent risk factors.

4.
Eur J Cardiothorac Surg ; 66(2)2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39073911

ABSTRACT

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a rescue for refractory cardiac arrest, of which acute coronary syndrome is a common cause. Data on the coronary revascularization strategy in patients receiving ECPR remain limited. METHODS: The ECPR databases from two referral hospitals were screened for patients who underwent emergent revascularization. The baseline characteristics were matched 1:1 using propensity score between patients who underwent coronary artery bypass grafting (CABG) and those who received percutaneous coronary intervention (PCI). Outcomes, including success rate of weaning from extracorporeal membrane oxygenation (ECMO), hospital survival, and midterm survival in hospital survivors, were compared between CABG and PCI. RESULTS: After matching, most of the patients (95%) had triple vessel disease. Compared with PCI (n = 40), emergent CABG (n = 40) had better early outcomes, in terms of the rates of successful ECMO weaning (71.1% vs 48.7%, P = 0.05) and hospital survival (56.4% versus 32.4%, P = 0.04). After a mean follow-up of 2 years, both revascularization strategies were associated with favourable midterm survival among hospital survivors (75.3% after CABG vs 88.9% after PCI, P = 0.49), with a trend towards fewer reinterventions in patients who underwent CABG (P = 0.07). CONCLUSIONS: In patients who received ECPR because of triple vessel disease, the hospital outcomes were better after emergent CABG than after PCI. More evidence is required to determine the optimal revascularization strategy for patients who receive ECPR.


Subject(s)
Cardiopulmonary Resuscitation , Coronary Artery Bypass , Extracorporeal Membrane Oxygenation , Percutaneous Coronary Intervention , Humans , Male , Female , Percutaneous Coronary Intervention/methods , Percutaneous Coronary Intervention/statistics & numerical data , Coronary Artery Bypass/statistics & numerical data , Coronary Artery Bypass/methods , Middle Aged , Extracorporeal Membrane Oxygenation/methods , Extracorporeal Membrane Oxygenation/statistics & numerical data , Cardiopulmonary Resuscitation/methods , Cardiopulmonary Resuscitation/statistics & numerical data , Aged , Retrospective Studies , Treatment Outcome , Coronary Artery Disease/surgery
5.
Free Radic Biol Med ; 222: 588-600, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38996820

ABSTRACT

Emerging evidence has reported that acute lung injury (ALI), characterized by inflammation and oxidative stress in airway epithelium, is regulated by programmed cell death. Ferroptosis, a regulated form of cell death spurred by uncontrolled lipid peroxidation, has been proven to implicate various diseases. Inhibiting ferroptosis represents a feasible strategy for ALI through the suppression of lipid peroxidation, while the mechanism remains to be further elucidated. Here, we identified Sequestosome 1 (SQSTM1) as a negative regulator of airway epithelium ferroptosis during ALI. SQSTM1 knockdown cells manifested higher sensitivity to ferroptosis. Mechanistically, SQSTM1 was found to directly interact with vitamin D receptor (VDR) through its nuclear receptor (NR) box motif, facilitating its nuclear translocation and initiating autophagy at the transcriptional level. To further validate these findings, an in vivo preventive model utilizing spermidine, a proven inducer of SQSTM1 was established. The results consistently demonstrated that spermidine supplementation significantly induced SQSTM1 and ameliorated ALI by mitigating airway epithelial ferroptosis. Notably, these effects were abrogated in the absence of SQSTM1. Taken together, this study identified SQSTM1 as a negative regulator of airway epithelium ferroptosis in a VDR-mediated autophagy manner, making it a potential therapeutic target for the treatment of ALI.

6.
Eur Spine J ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907066

ABSTRACT

PURPOSE: This study aimed to consolidate the evidence regarding the prognostic influence of sarcopenia in degenerative lumbar spine surgeries. METHODS: A literature search of public databases was conducted up to Nov 15, 2023 using combinations of the key words "sarcopenia" and "lumbar spine surgery". Eligible studies were those that focused on adults undergoing decompression or fusion surgery for degenerative lumbar spine diseases, and compared the outcomes between patients with and without preoperative sarcopenia. Primary outcomes were change in ODI and back and leg pain VAS pain scores. Secondary outcomes were changes in Eq. 5D, JOA, SFHS-p scores, and LOS. RESULTS: Ultimately, nine retrospective studies with a total of 993 patients were included. Sarcopenic patients exhibited significantly worse functional improvement as assessed by ODI compared to non-sarcopenic patients (pooled standardized mean difference [pSMD] = 0.53, 95% confidence interval [CI]: 0.17-0.90). Back pain (pSMD = 0.31, 95% CI:0.15-0.47) and leg pain (pSMD = 0.21, 95% CI:0.02 - 0.39) improvement were also less in sarcopenic patients. Non-sarcopenic patients had greater improvements in Eq. 5D (pSMD = 0.25) and SFHS-p (pSMD = 0.39), and shorter LOS (pSMD = 0.62). CONCLUSIONS: As compared to patients without sarcopenia, those with sarcopenia undergoing lumbar spine surgery for degenerative diseases have lower improvements in functional ability, quality of life, physical health, pain relief and extended hospitalization compared to those without sarcopenia.

7.
Small ; : e2402981, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38838089

ABSTRACT

To address the imperative challenge of producing hydrogen in a low-energy consumption electrocatalytic system, this study emphasizes the utilization of thermodynamically favorable biomass oxidation for achieving energy-efficient hydrogen generation. This research integrates ultralow PtO2-loaded flower-like nanosheets (denoted as PtO2@Cu2O/Cu FNs) with Cu0/Cu+ pairs and Pt─O bonds, thereby yielding substantial enhancement in both hydrogen evolution reaction (HER, -0.042 VRHE at 10 mA cm-2) and furfural oxidation reaction (FFOR, 0.09 VRHE at 10 mA cm-2). As validated by DFT calculations, the dual built-in electric field (BIEF) is elucidated as the driving force behind the enhanced activities, in which Pt─O bonds expedite the HER, while Cu+/Cu0 promotes low-potential FFOR. By coupling the FFOR and HER together, the resulting bipolar-hydrogen production system requires a low power input (0.5072 kWh per m3) for producing H2. The system can generate bipolar hydrogen and high value-added furoic acid, significantly enhancing hydrogen production efficiency and concurrently mitigating energy consumption.

8.
Bioorg Chem ; 150: 107594, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38941701

ABSTRACT

Inhibition of human dihydroorotate dehydrogenase (hDHODH) represents a promising strategy for suppressing the proliferation of cancer cells. To identify novel and potent hDHODH inhibitors, a total of 28 piperine derivatives were designed and synthesized. Their cytotoxicities against three human cancer cell lines (NCI-H226, HCT-116, and MDA-MB-231) and hDHODH inhibitory activities were also evaluated. Among them, compound H19, exhibited the strongest inhibitory activities (NCI-H226 IC50 = 0.95 µM, hDHODH IC50 = 0.21 µM). Further pharmacological investigations revealed that H19 exerted anticancer effects by inducing ferroptosis in NCI-H226 cells, with its cytotoxicity being reversed by ferroptosis inhibitors. This was supported by the intracellular growth or decline of ferroptosis markers, including lipid peroxidation, Fe2+, GSH, and 4-HNE. Overall, H19 emerges as a promising hDHODH inhibitor with potential anticancer properties warranting development.


Subject(s)
Alkaloids , Antineoplastic Agents , Benzodioxoles , Cell Proliferation , Dihydroorotate Dehydrogenase , Drug Screening Assays, Antitumor , Enzyme Inhibitors , Ferroptosis , Piperidines , Polyunsaturated Alkamides , Humans , Alkaloids/pharmacology , Alkaloids/chemistry , Alkaloids/chemical synthesis , Dihydroorotate Dehydrogenase/antagonists & inhibitors , Piperidines/pharmacology , Piperidines/chemistry , Piperidines/chemical synthesis , Benzodioxoles/pharmacology , Benzodioxoles/chemical synthesis , Benzodioxoles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Structure-Activity Relationship , Ferroptosis/drug effects , Cell Proliferation/drug effects , Polyunsaturated Alkamides/pharmacology , Polyunsaturated Alkamides/chemistry , Polyunsaturated Alkamides/chemical synthesis , Molecular Structure , Dose-Response Relationship, Drug , Drug Discovery , Cell Line, Tumor
9.
Ying Yong Sheng Tai Xue Bao ; 35(4): 1123-1130, 2024 Apr 18.
Article in Chinese | MEDLINE | ID: mdl-38884247

ABSTRACT

China has complex natural conditions and is rich in biodiversity. Based on the geographical distribution and species composition of terrestrial mammals, we explored the characteristics and geographic partitioning of mammal populations in different regions of China. We used a clustering algorithm, combined with the spatial distribution data and taxonomic characteristics of mammals, to geographically partition the terrestrial mammals in China. We found 10 zoogeographic regions of terrestrial mammals in China: Northeast region, North China region, Eastern grassland region, Western region, Northwest region, Qiangtang plateau region, Eastern Qinghai-Tibet Plateau region, Himalayan region, South China region, and Taiwan-Hainan region. We found a new geographical zoning pattern for terrestrial mammals in China, examined the variability and characteristics of species composition among different regions, and quantified the association between species distribution and environmental factors. We proposed a method of incorporating taxonomic information into cluster analysis, which provided a new idea for zoogeographic region studies, a new perspective for understanding species diversity, and a scientific basis for animal conservation and habitat planning.


Subject(s)
Biodiversity , Ecosystem , Mammals , China , Animals , Mammals/classification , Geography , Cluster Analysis , Conservation of Natural Resources
11.
Se Pu ; 42(5): 410-419, 2024 Apr 08.
Article in Chinese | MEDLINE | ID: mdl-38736384

ABSTRACT

Protein A affinity chromatographic materials are widely used in clinical medicine and biomedicine because of their specific interactions with immunoglobulin G (IgG). Both the characteristics of the matrix, such as its structure and morphology, and the surface modification method contribute to the affinity properties of the packing materials. The specific, orderly, and oriented immobilization of protein A can reduce its steric hindrance with the matrix and preserve its bioactive sites. In this study, four types of affinity chromatographic materials were obtained using agarose and polyglycidyl methacrylate (PGMA) spheres as substrates, and multifunctional epoxy and maleimide groups were used to fix protein A. The effects of the ethylenediamine concentration, reaction pH, buffer concentration, and other conditions on the coupling efficiency of protein A and adsorption performance of IgG were evaluated. Multifunctional epoxy materials were prepared by converting part of the epoxy groups of the agarose and PGMA matrices into amino groups using 0.2 and 1.6 mol/L ethylenediamine, respectively. Protein A was coupled to the multifunctional epoxy materials using 5 mmol/L borate buffer (pH 8) as the reaction solution. When protein A was immobilized on the substrates by maleimide groups, the agarose and PGMA substrates were activated with 25% (v/v) ethylenediamine for 16 h to convert all epoxy groups into amino groups. The maleimide materials were then converted into amino-modified materials by adding 3 mg/mL 3-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) dissolved in dimethyl sulfoxide (DMSO) and then suspended in 5 mmol/L borate buffer (pH 8). The maleimide groups reacted specifically with the C-terminal of the sulfhydryl group of recombinant protein A to achieve highly selective fixation on both the agarose and PGMA substrates. The adsorption performance of the affinity materials for IgG was improved by optimizing the bonding conditions of protein A, such as the matrix type, matrix particle size, and protein A content, and the adsorption properties of each affinity material for IgG were determined. The column pressure of the protein A affinity materials prepared using agarose or PGMA as the matrix via the maleimide method was subsequently evaluated at different flow rates. The affinity materials prepared with PGMA as the matrix exhibited superior mechanical strength compared with the materials prepared with agarose. Moreover, an excellent linear relationship between the flow rate and column pressure of 80 mL/min was observed for this affinity material. Subsequently, the effect of the particle size of the PGMA matrix on the binding capacity of IgG was investigated. Under the same protein A content, the dynamic binding capacity of the affinity materials on the PGMA matrix was higher when the particle size was 44-88 µm than when other particle sizes were used. The properties of the affinity materials prepared using the multifunctional epoxy and maleimide-modified materials were compared by synthesizing affinity materials with different protein A coupling amounts of 1, 2, 4, 6, 8, and 10 mg/mL. The dynamic and static binding capacities of each material for bovine IgG were then determined. The prepared affinity material was packed into a chromatographic column to purify IgG from bovine colostrum. Although all materials showed specific adsorption selectivity for IgG, the affinity material prepared by immobilizing protein A on the PGMA matrix with maleimide showed significantly better performance and achieved a higher dynamic binding capacity at a lower protein grafting amount. When the protein grafting amount was 15.71 mg/mL, the dynamic binding capacity of bovine IgG was 32.23 mg/mL, and the dynamic binding capacity of human IgG reached 54.41 mg/mL. After 160 cycles of alkali treatment, the dynamic binding capacity of the material reached 94.6% of the initial value, indicating its good stability. The developed method is appropriate for the production of protein A affinity chromatographic materials and shows great potential in the fields of protein immobilization and immunoadsorption material synthesis.


Subject(s)
Chromatography, Affinity , Staphylococcal Protein A , Chromatography, Affinity/methods , Staphylococcal Protein A/chemistry , Adsorption , Immunoglobulin G/chemistry , Polymethacrylic Acids/chemistry , Sepharose/chemistry
12.
Pharmgenomics Pers Med ; 17: 237-249, 2024.
Article in English | MEDLINE | ID: mdl-38807628

ABSTRACT

Background: Rheumatoid arthritis (RA) is a common autoimmune disease with the main symptoms being joint swelling and pain. In severe cases, joint deformity or even complete loss of function occurs. Technetium methylene diphosphonate (99Tc-MDP) is widely used for RA treatment in China, but there are no studies on the effects of 99Tc-MDP on intestinal flora. Objective: To explore the effects of 99Tc-MDP treatment on the composition and function of the intestinal flora and to provide new information on the mechanism of 99Tc-MDP in RA treatment. Methods: Stool samples from RA patients before and after 99Tc-MDP treatment were collected to form two groups (Before and After). Total genomic DNA of the samples was extracted for 16S rRNA gene sequencing. The altered composition of the intestinal flora, the key target bacteria regulated by 99Tc-MDP, and the pathways of action of 99 Tc-MDP were analyzed by bioinformatics. Results: A total of 64 fresh stool samples were collected from 32 RA patients. Compared to the Before group, the After group showed increased Bacteroidetes abundance and decreased Firmicutes abundance. At the genus level, Prevotella increased whereas Escherichia decreased. Both α and ß diversity analyses showed that 99Tc-MDP treatment did not affect gut microbial diversity in RA patients. LEfSe analyses and random forest analyses showed Bacteroidetes, Prevotella, Enterococcus, Escherichia and Ruminococcaceae were the main 99Tc-MDP regulating bacteria. Functional enrichment analysis revealed that the functional differences in gut flora of the two groups centered on Metabolism and Genetic Information Processing. Conclusion: This study revealed differences in the composition of the gut microbiota in RA patients before and after 99Tc-MDP treatment. The therapeutic effect of 99Tc MDP is mainly achieved through Bacteroidetes, Prevotella, and Enterococcus. Regulating metabolism and genetic information processing of gut flora may be the mechanism of 99Tc-MDP in treating RA.

13.
Fitoterapia ; 176: 105985, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38705541

ABSTRACT

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.


Subject(s)
Hypericum , Monoterpenes , Phloroglucinol , Phytochemicals , Hypericum/chemistry , Mice , Molecular Structure , Monoterpenes/isolation & purification , Monoterpenes/pharmacology , Phloroglucinol/isolation & purification , Phloroglucinol/pharmacology , Phloroglucinol/chemistry , RAW 264.7 Cells , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Animals , Nitric Oxide/metabolism , Stereoisomerism , China
14.
STAR Protoc ; 5(2): 103047, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38691463

ABSTRACT

The tumor-associated mucin MUC1 is overexpressed in almost all types of epithelial tumor tissues, making it an attractive target antigen for cancer immunotherapy. Here we present a protocol to prepare MUC1 glycopeptide vaccines and to evaluate immunization effects in mice. We describe steps for synthesizing glycopeptide antigen and conjugating it with carrier protein to make vaccine candidates. We then detail procedures for mice immunization, antibody response evaluation, and cellular immune response. For complete details on the use and execution of this protocol, please refer to Cai et al.1,2.


Subject(s)
Cancer Vaccines , Glycopeptides , Mucin-1 , Animals , Mucin-1/immunology , Mice , Glycopeptides/immunology , Cancer Vaccines/immunology , Immunization/methods , Female
15.
Environ Technol ; : 1-13, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773903

ABSTRACT

The increasing concentrations of heavy metals in livestock wastewater pose a serious threat to the environmental safety and human health, limiting its resource utilisation. In the present study, microalgae and nanoscale zero-valent iron were selected to construct a coupled system for copper-containing wastewater treatment. The addition of 50 mg·L-1 nanoscale zero-valent iron (50 nm) was the optimal value for the experiment, which could significantly increase the biomass of microalgae. In addition, nanoscale zero-valent iron stimulated microalgal secretion of extracellular polymeric substances, increasing the contents of binding sites, organic ligands, and functional groups on the microalgal surfaces and ultimately promoting the settling of microalgae and binding of heavy metals. The coupled system could quickly adapt to copper-containing wastewater of 10 mg·L-1, and the copper removal rate reached 94.99%. Adsorption and uptake by organisms, together with the contribution of zero-valent iron nanoparticles, are the major copper removal pathways. Overall, this work offers a novel technical solution for enhanced treatment of copper-containing livestock wastewater, which will help improve the efficiency and quality of wastewater treatment.

16.
Int Immunopharmacol ; 133: 112041, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38636373

ABSTRACT

Although the pathogenesis of rheumatoid arthritis (RA) remains unclear, an increasing number of studies have confirmed that pyroptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is an important factor affecting the progression of RA. Periplogenin (PPN) is a natural cardiac glycoside; reportedly, it exerts anti-inflammatory and analgesic effects in diseases by inhibiting cell growth and migration. This study aimed to determine the effect of PPN on the growth, migration, and invasion of RA-FLS and the potential mechanism of pyroptosis regulation. We discovered that PPN could inhibit the migration and invasion abilities of RA-FLS and block their growth cycle, down-regulate the secretion and activation of NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18, and reduce the number of pyroptosis. In summary, PPN inhibited pyroptosis, reduced the release of inflammatory factors, and improved RA-FLS inflammation by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.


Subject(s)
Arthritis, Rheumatoid , Fibroblasts , Pyroptosis , Signal Transduction , Synoviocytes , Humans , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Caspase 1/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Fibroblasts/drug effects , Gasdermins , Intracellular Signaling Peptides and Proteins/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Phosphate-Binding Proteins/metabolism , Pyroptosis/drug effects , Signal Transduction/drug effects , Synoviocytes/drug effects , Synoviocytes/metabolism , Synoviocytes/pathology
17.
Int J Antimicrob Agents ; 63(6): 107172, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38608845

ABSTRACT

OBJECTIVES: This study aimed to discover novel antifungals targeting Candida albicans glyceraldehyde-3-phosphate dehydrogenase (CaGAPDH), have an insight into inhibitory mode, and provide evidence supporting CaGAPDH as a target for new antifungals. METHODS: Virtual screening was utilized to discover inhibitors of CaGAPDH. The inhibitory effect on cellular GAPDH was evaluated by determining the levels of ATP, NAD, NADH, etc., as well as examining GAPDH mRNA and protein expression. The role of GAPDH inhibition in C. albicans was supported by drug affinity responsive target stability and overexpression experiments. The mechanism of CaGAPDH inhibition was elucidated by Michaelis-Menten enzyme kinetics and site-specific mutagenesis based on docking. Chemical synthesis was used to produce an improved candidate. Different sources of GAPDH were used to evaluate inhibitory selectivity across species. In vitro and in vivo antifungal tests, along with anti-biofilm activity, were carried out to evaluate antifungal potential of GAPDH inhibitors. RESULTS: A natural xanthone was identified as the first competitive inhibitor of CaGAPDH. It demonstrated in vitro anti-C. albicans potential but also caused hemolysis. XP-W, a synthetic side-chain-optimized xanthone, demonstrated a better safety profile, exhibiting a 50-fold selectivity for CaGAPDH over human GAPDH. XP-W also exhibited potent anti-biofilm activity and displayed broad-spectrum anti-Candida activities in vitro and in vivo, including multi-azole-resistant C. albicans. CONCLUSIONS: These results demonstrate for the first time that CaGAPDH is a valuable target for antifungal drug discovery, and XP-W provides a promising lead.


Subject(s)
Antifungal Agents , Candida albicans , Glyceraldehyde-3-Phosphate Dehydrogenases , Xanthones , Candida albicans/drug effects , Candida albicans/enzymology , Xanthones/pharmacology , Xanthones/chemistry , Antifungal Agents/pharmacology , Glyceraldehyde-3-Phosphate Dehydrogenases/antagonists & inhibitors , Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism , Glyceraldehyde-3-Phosphate Dehydrogenases/genetics , Animals , Biofilms/drug effects , Microbial Sensitivity Tests , Humans , Candidiasis/drug therapy , Candidiasis/microbiology , Molecular Docking Simulation , Enzyme Inhibitors/pharmacology , Mice , Drug Discovery
18.
Genome Biol ; 25(1): 97, 2024 04 15.
Article in English | MEDLINE | ID: mdl-38622738

ABSTRACT

BACKGROUND: As most viruses remain uncultivated, metagenomics is currently the main method for virus discovery. Detecting viruses in metagenomic data is not trivial. In the past few years, many bioinformatic virus identification tools have been developed for this task, making it challenging to choose the right tools, parameters, and cutoffs. As all these tools measure different biological signals, and use different algorithms and training and reference databases, it is imperative to conduct an independent benchmarking to give users objective guidance. RESULTS: We compare the performance of nine state-of-the-art virus identification tools in thirteen modes on eight paired viral and microbial datasets from three distinct biomes, including a new complex dataset from Antarctic coastal waters. The tools have highly variable true positive rates (0-97%) and false positive rates (0-30%). PPR-Meta best distinguishes viral from microbial contigs, followed by DeepVirFinder, VirSorter2, and VIBRANT. Different tools identify different subsets of the benchmarking data and all tools, except for Sourmash, find unique viral contigs. Performance of tools improved with adjusted parameter cutoffs, indicating that adjustment of parameter cutoffs before usage should be considered. CONCLUSIONS: Together, our independent benchmarking facilitates selecting choices of bioinformatic virus identification tools and gives suggestions for parameter adjustments to viromics researchers.


Subject(s)
Benchmarking , Viruses , Metagenome , Ecosystem , Metagenomics/methods , Computational Biology/methods , Databases, Genetic , Viruses/genetics
19.
Front Pediatr ; 12: 1372980, 2024.
Article in English | MEDLINE | ID: mdl-38562136

ABSTRACT

Objective: The acquisition of fine motor skills is considered to be a crucial developmental milestone throughout early childhood. This study aimed to investigate the fine motor performance of young children with different disability diagnoses. Methods: We enrolled a sample of 1,897 young children under the age of 6 years who were at risk of developmental delays and were identified by a transdisciplinary team. A series of standardized developmental assessments included the Bayley Scales of Infant Development-Third Edition, Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition, Peabody Developmental Motor Scale-Second Edition, and Movement Assessment Battery for Children-Second Edition were used. Retrospective chart reviews were conducted on all children to identify specific developmental disorders. The number of autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), comorbidity, motor dysfunction, and unspecified developmental delays (DD) were 363 (19.1%), 223 (11.8%), 234 (12.3%), 285 (15.0%), 128 (6.7%), and 590 (31.1%), respectively. Results: Young children with ID, comorbidity, and motor dysfunction demonstrated significant difficulty in performing manual dexterity and visual motor integration tasks and scored significantly lower in these areas than children with ASD, ADHD, and unspecified DD. In addition, fine motor performance was associated with cognitive ability in children with different disability diagnoses, indicating that young children showed better fine motor performance when they demonstrated better cognitive ability. Conclusion: Our findings support that differences in fine motor performance differ by disability type. Close links between fine motor performance and cognitive ability in children under the age of 6 years were seen in all disability types.

20.
Chem Sci ; 15(14): 5192-5200, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38577355

ABSTRACT

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

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