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1.
Trials ; 25(1): 352, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822360

ABSTRACT

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disorder characterized by pain and functional impairment. Blood flow restriction (BFR) with low-load resistance training (LLRT) demonstrates a similar improvement in clinical outcomes to high-load resistance training (HLRT) in treating KOA. It has not been established whether intermittent blood flow restriction (iBFR) with LLRT can lead to clinical outcomes that are comparable to those produced by continuous blood flow restriction (cBFR) with LLRT and HLRT. The aim of the proposed study is to evaluate the efficacy of iBFR with LLRT on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence in KOA patients. METHODS: This is a three-arm, non-inferiority, randomized controlled trial utilizing blinded assessors. Two hundred thirteen participants will be randomly allocated to one of the following three groups: iBFR group-receiving 4 months of LLRT with iBFR, twice weekly (n = 71); cBFR group-receiving 4 months of LLRT with cBFR, twice weekly (n = 71); or HLRT group-receiving 4 months of HLRT without BFR, twice weekly (n = 71). The primary outcome is pain. The secondary outcomes include the WOMAC, muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence. Pain and WOMAC will be measured at the baseline and 4 and 12 months after randomizations. Muscle strength, muscle mass, and physical function will be measured at the baseline and 4 months after randomizations. The perceptions of discomfort and effort will be measured during the first and final sessions. DISCUSSION: BFR with LLRT has a similar improvement in clinical outcomes as HLRT. However, cBFR may cause elevated ratings of perceived exertion and local discomfort, compromising patient tolerability and treatment adherence. If iBFR with LLRT could produce improvement in clinical outcomes analogous to those of HLRT and iBFR with LLRT, it could be considered an alternative approach for treating patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300072820. Registered on June 26, 2023.


Subject(s)
Blood Flow Restriction Therapy , Muscle Strength , Osteoarthritis, Knee , Resistance Training , Humans , Resistance Training/methods , Osteoarthritis, Knee/physiopathology , Osteoarthritis, Knee/therapy , Aged , Treatment Outcome , Blood Flow Restriction Therapy/methods , Female , Male , Middle Aged , Equivalence Trials as Topic , Pain Measurement , Regional Blood Flow , Randomized Controlled Trials as Topic , Recovery of Function , Time Factors , Knee Joint/physiopathology
2.
Nat Commun ; 15(1): 4703, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830868

ABSTRACT

Nuclear factor erythroid 2-related factor 2 (NRF2) hyperactivation has been established as an oncogenic driver in a variety of human cancers, including non-small cell lung cancer (NSCLC). However, despite massive efforts, no specific therapy is currently available to target NRF2 hyperactivation. Here, we identify peptidylprolyl isomerase A (PPIA) is required for NRF2 protein stability. Ablation of PPIA promotes NRF2 protein degradation and blocks NRF2-driven growth in NSCLC cells. Mechanistically, PPIA physically binds to NRF2 and blocks the access of ubiquitin/Kelch Like ECH Associated Protein 1 (KEAP1) to NRF2, thus preventing ubiquitin-mediated degradation. Our X-ray co-crystal structure reveals that PPIA directly interacts with a NRF2 interdomain linker via a trans-proline 174-harboring hydrophobic sequence. We further demonstrate that an FDA-approved drug, cyclosporin A (CsA), impairs the interaction of NRF2 with PPIA, inducing NRF2 ubiquitination and degradation. Interestingly, CsA interrupts glutamine metabolism mediated by the NRF2/KLF5/SLC1A5 pathway, consequently suppressing the growth of NRF2-hyperactivated NSCLC cells. CsA and a glutaminase inhibitor combination therapy significantly retard tumor progression in NSCLC patient-derived xenograft (PDX) models with NRF2 hyperactivation. Our study demonstrates that targeting NRF2 protein stability is an actionable therapeutic approach to treat NRF2-hyperactivated NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Kelch-Like ECH-Associated Protein 1 , Lung Neoplasms , NF-E2-Related Factor 2 , Protein Stability , Ubiquitination , NF-E2-Related Factor 2/metabolism , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Animals , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Mice , Cell Line, Tumor , Disease Progression , Proteolysis , Mice, Nude , Female , NIMA-Interacting Peptidylprolyl Isomerase
3.
RSC Adv ; 14(25): 17929-17944, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38836170

ABSTRACT

Cancer has become the leading cause of death worldwide. In recent years, molecular diagnosis has demonstrated great potential in the prediction and diagnosis of cancer. MicroRNAs (miRNAs) are short oligonucleotides that regulate gene expression and cell function and are considered ideal biomarkers for cancer detection, diagnosis, and patient prognosis. Therefore, the specific and sensitive detection of ultra-low quantities of miRNA is of great significance. MiRNA biosensors based on electrochemical technology have advantages of high sensitivity, low cost and fast response. Nanomaterials show great potential in miRNA electrochemical detection and promote the rapid development of electrochemical miRNA biosensors. Some methods and signal amplification strategies for miRNA detection in recent years are reviewed herein, followed by a discussion of the latest progress in electrochemical miRNA detection based on different types of nanomaterial. Future perspectives and challenges are also proposed for further exploration of nanomaterials to bring breakthroughs in electrochemical miRNA detection.

4.
Sci Rep ; 14(1): 10405, 2024 05 06.
Article in English | MEDLINE | ID: mdl-38710809

ABSTRACT

As the most popular sport among middle-aged and elderly women in China, square dancing has both physical and psychological benefits for menopausal women. Previous studies have shown that square dance exercises can promote the physical health of older women, but there is a lack of research on the influence of middle-aged and elderly women on mental health and mediating variables. Therefore, this study starts with one of the important indicators of mental health-positive affects, aiming to explore the impact of square dance on the positive emotions of elderly women and further explore the mediating mechanisms involved. We send out The Physical Activity Rating Scale, the Positive and Negative Affect Scale, the Connor-Davidson Resilience Scale, and the Satisfaction With Life Scale to a total of 2311 middle-aged and elderly women. SPSS 23 software and PROCESS were used to perform regression analysis and establish mediation models. Modeling results show square dance exercises could positively predict positive affect through the chain mediating effect of psychological resilience and life satisfaction. The results of this study are of great significance for promoting the extensive participation of middle-aged and elderly women in sports and protecting their mental health.


Subject(s)
Dancing , Mental Health , Personal Satisfaction , Humans , Female , Dancing/psychology , Middle Aged , Aged , Aging/psychology , Exercise/psychology , China , Resilience, Psychological , Quality of Life , Psychological Well-Being
6.
Mil Med Res ; 11(1): 31, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38797843

ABSTRACT

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.


Subject(s)
Aging , Genomics , Proteomics , Regenerative Medicine , Aging/physiology , Humans , Regenerative Medicine/methods , Regenerative Medicine/trends , Genomics/methods , Proteomics/methods , Metabolomics/methods , Epigenomics/methods , Multiomics
8.
J Multidiscip Healthc ; 17: 2031-2038, 2024.
Article in English | MEDLINE | ID: mdl-38706503

ABSTRACT

Background: Patients on maintenance hemodialysis have an increased risk of fracture. However, the relationship between fracture and poor prognosis is not clear. Methods: A total of 182 maintenance hemodialysis patients were enrolled in the study. The relationship between fracture and poor prognosis (cardiovascular events, stroke, malignancy and 5-year all-cause mortality) were analyzed. Results: 21 of 182 patients had a history of fracture at the time of enrollment. 26 patients had a new fracture after enrollment. A total of 57 fractures occurred in 47 patients, the most common fracture site was the rib. Patients with fracture group had a higher proportion of elderly and female, higher serum phosphorus and B-type natriuretic peptide and lower hemoglobin, albumin, and potassium compared with those without fracture. Age (OR=3.809, 95% CI: 1.064-8.966, p=0.038), hemoglobin (OR=0.961, 95% CI: 0.925-0.997, p=0.035), and serum phosphorus (OR=3.325, 95% CI:1.104-10.019, p=0.033) were the independent risk factors of new fractures in MHD patients. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture (p<0.05). But there was no significant difference in the incidence of acute myocardial infarction or stroke. Conclusion: 25.8% of maintenance hemodialysis patients had at least one fracture, with rib fractures accounting for the highest proportion. Age, hemoglobin and serum phosphorus were the independent risk factors of new fractures. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture, but there was no significant difference in the incidence of acute myocardial infarction and stroke.


To determine the incidence of fractures in hemodialysis patients, we conducted this single center, prospective observational study. 182 patients were enrolled. We also recorded the 5-year incidence of acute myocardial infarction(AMI), stroke, malignancy, and mortality. Our results showed that the incidence of fracture in hemodialysis patients was 25.8%. The most common fracture site was the rib. There were significant statistical differences in age, gender, hemoglobin, serum albumin, B-type natriuretic peptide, potassium and phosphorus between patients with and without fractures. Logistic regression analysis suggested that advanced age, anaemia and hyperphosphatemia were independent risk factors for new fractures in hemodialysis patients. We followed 182 patients for 5 years and recorded the incidence of stroke, AMI and malignancy. The rates of AMI and stroke did not differ significantly between the two groups. However, the incidence of malignancy in patients with fractures is significantly higher than that in patients without fractures. In our study, a total of 74 patients died, including 24 deaths in the fracture group and 50 deaths in the non-fracture group. The main causes of death in 74 cases were cardiovascular events. Our study provides some insight into the association between fractures and poor outcomes in hemodialysis patients.

10.
Front Cell Infect Microbiol ; 14: 1367975, 2024.
Article in English | MEDLINE | ID: mdl-38736750

ABSTRACT

The endemic outbreak of SADS-CoV has resulted in economic losses and potentially threatened the safety of China's pig industry. The molecular epidemiology of SADS-CoV in pig herds has been investigated in many provinces in China. However, there are no data over a long-time span, and there is a lack of extensive serological surveys to assess the prevalence of SADS-CoV in Chinese swine herds since the discovery of SADS-CoV. In this study, an indirect anti-SADS-CoV IgG enzyme-linked immunosorbent assay (ELISA) based on the SADS-CoV S1 protein was established to investigate the seroprevalence of SADS-CoV in Chinese swine herds. Cross-reactivity assays, indirect immunofluorescence, and western blotting assays showed that the developed ELISA had excellent SADS-CoV specificity. In total, 12,978 pig serum samples from 29 provinces/municipalities/autonomous regions in China were tested from 2022 to 2023. The results showed that the general seroprevalence of SADS-CoV in China was 59.97%, with seroprevalence ranging from 16.7% to 77.12% in different provinces and from 42.61% to 68.45% in different months. SADS-CoV is widely prevalent in China, and its seroprevalence was higher in Northeast China, North China, and Central China than in other regions. Among the four seasons, the prevalence of SADS-CoV was the highest in spring and the lowest in autumn. The results of this study provide the general seroprevalence profile of SADS-CoV in China, facilitating the understanding of the prevalence of SADS-CoV in pigs. More importantly, this study is beneficial in formulating preventive and control measures for SADS-CoV and may provide directions for vaccine development.


Subject(s)
Antibodies, Viral , Coronavirus Infections , Enzyme-Linked Immunosorbent Assay , Swine Diseases , Animals , China/epidemiology , Seroepidemiologic Studies , Swine , Enzyme-Linked Immunosorbent Assay/methods , Antibodies, Viral/blood , Swine Diseases/epidemiology , Swine Diseases/virology , Coronavirus Infections/veterinary , Coronavirus Infections/epidemiology , Coronavirus Infections/diagnosis , Immunoglobulin G/blood , Alphacoronavirus/immunology , Alphacoronavirus/genetics , Cross Reactions , Sensitivity and Specificity
11.
Cell Mol Immunol ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740925

ABSTRACT

The NLRP3 inflammasome functions as an inflammatory driver, but its relationship with lipid metabolic changes in early sepsis remains unclear. Here, we found that GITR expression in monocytes/macrophages was induced by lysophosphatidylcholine (LPC) and was positively correlated with the severity of sepsis. GITR is a costimulatory molecule that is mainly expressed on T cells, but its function in macrophages is largely unknown. Our in vitro data showed that GITR enhanced LPC uptake by macrophages and specifically enhanced NLRP3 inflammasome-mediated macrophage pyroptosis. Furthermore, in vivo studies using either cecal ligation and puncture (CLP) or LPS-induced sepsis models demonstrated that LPC exacerbated sepsis severity/lethality, while conditional knockout of GITR in myeloid cells or NLRP3/caspase-1/IL-1ß deficiency attenuated sepsis severity/lethality. Mechanistically, GITR specifically enhanced inflammasome activation by regulating the posttranslational modification (PTM) of NLRP3. GITR competes with NLRP3 for binding to the E3 ligase MARCH7 and recruits MARCH7 to induce deacetylase SIRT2 degradation, leading to decreasing ubiquitination but increasing acetylation of NLRP3. Overall, these findings revealed a novel role of macrophage-derived GITR in regulating the PTM of NLRP3 and systemic inflammatory injury, suggesting that GITR may be a potential therapeutic target for sepsis and other inflammatory diseases. GITR exacerbates LPC-induced macrophage pyroptosis in sepsis via posttranslational regulation of NLRP3. According to the model, LPC levels increase during the early stage of sepsis, inducing GITR expression on macrophages. GITR not only competes with NLRP3 for binding to the E3 ligase MARCH7 but also recruits MARCH7 to induce the degradation of the deacetylase SIRT2, leading to decreasing ubiquitination but increasing acetylation of NLRP3 and therefore exacerbating LPC-induced NLRP3 inflammasome activation, macrophage pyroptosis and systemic inflammatory injury.

12.
PLoS One ; 19(5): e0302498, 2024.
Article in English | MEDLINE | ID: mdl-38758804

ABSTRACT

BACKGROUND: Medical Waste (MW), conceptualized as waste generated in the diagnosis, treatment, or immunization of human beings or animals, posing massive threat to public health. Environment-friendly public attitudes promotes the shaping of pro-environmental behavior. However, the public attitudes of MW and the potential determinants remained scarce. The present study aims to reveal globally public attitudes towards MW and captured the determinants. METHODS: We integrated the crawler technology with sentiment analysis to captured the public attitudes toward MW across 141 specific countries from 3,789,764 related tweets. Multiple cross-national databases were integrated to assess characteristics including risk, resistance, environment, and development. The spatial regression model was taken to counterbalence the potential statistical bias. RESULTS: Overall, the global public attitudes towards MW were positive, and varied significantly across countries. Resilience (ß = 0.78, SD = 0.14, P < 0.01) and development (ß = 1.66, SD = 0.13, P < 0.01) posed positive influence on public attitudes towards MW, meanwhile, risk (ß = -0.1, SD = 0.12, P > 0.05) and environment (ß = 0.09, SD = 0.09, P > 0.05) were irrelated to the shaping of positive MW public attitudes. Several positive moderating influences was also captured. Additionally, the cross-national disparities of the determiants were also captured, more specific, public attitudes towards MW in extremely poor areas were more likely to be negatively affected by risks, resilience and development. CONCLUSIONS: This study focused mainly on the public attitudes as well as captured the potential determinants. Public attitudes towards MW were generally positive, but there were large cross-national disparities. Stakeholders would need to designate targeted strategies to enhance public satisfaction with MW management.


Subject(s)
Medical Waste , Public Opinion , Humans , Attitude , Medical Waste Disposal/methods
13.
J Biol Chem ; : 107379, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38762184

ABSTRACT

Bacterial RecJ exhibits 5'→3' exonuclease activity that is specific to single-stranded DNA (ssDNA); however, archaeal RecJs show 5' or 3' exonuclease activity. The hyperthermophilic archaea Methanocaldococcus jannaschii encodes the 5'-exonuclease MjRecJ1 and the 3'-exonuclease MjRecJ2. In addition to nuclease activity, archaeal RecJ interacts with GINS, a structural subcomplex of the replicative DNA helicase complex. However, MjRecJ1 and MjRecJ2 do not interact with MjGINS. Here, we report the structural basis for the inability of the MjRecJ2 homologous dimer to interact with MjGINS and its efficient 3' hydrolysis polarity for short dinucleotides. Based on the crystal structure of MjRecJ2, we propose that the interaction surface of the MjRecJ2 dimer overlaps the potential interaction surface for MjGINS and blocks the formation of the MjRecJ2-GINS complex. Exposing the interaction surface of the MjRecJ2 dimer restores its interaction with MjGINS. The cocrystal structures of MjRecJ2 with substrate dideoxynucleotides or product dCMP/CMP show that MjRecJ2 has a short substrate binding patch, which is perpendicular to the longer patch of bacterial RecJ. Our results provide new insights into the function and diversification of archaeal RecJ/Cdc45 proteins.

14.
Molecules ; 29(10)2024 May 09.
Article in English | MEDLINE | ID: mdl-38792078

ABSTRACT

Disuse muscle atrophy (DMA) is a significant healthcare challenge characterized by progressive loss of muscle mass and function resulting from prolonged inactivity. The development of effective strategies for muscle recovery is essential. In this study, we established a DMA mouse model through hindlimb suspension to evaluate the therapeutic potential of lactate in alleviating the detrimental effects on the gastrocnemius muscle. Using NMR-based metabolomic analysis, we investigated the metabolic changes in DMA-injured gastrocnemius muscles compared to controls and evaluated the beneficial effects of lactate treatment. Our results show that lactate significantly reduced muscle mass loss and improved muscle function by downregulating Murf1 expression, decreasing protein ubiquitination and hydrolysis, and increasing myosin heavy chain levels. Crucially, lactate corrected perturbations in four key metabolic pathways in the DMA gastrocnemius: the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; histidine metabolism; and arginine and proline metabolism. In addition to phenylalanine-related pathways, lactate also plays a role in regulating branched-chain amino acid metabolism and energy metabolism. Notably, lactate treatment normalized the levels of eight essential metabolites in DMA mice, underscoring its potential as a therapeutic agent against the consequences of prolonged inactivity and muscle wasting. This study not only advances our understanding of the therapeutic benefits of lactate but also provides a foundation for novel treatment approaches aimed at metabolic restoration and muscle recovery in conditions of muscle wasting.


Subject(s)
Lactic Acid , Metabolomics , Muscle, Skeletal , Animals , Mice , Metabolomics/methods , Lactic Acid/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/drug effects , Muscular Atrophy/metabolism , Muscular Atrophy/etiology , Muscular Atrophy/drug therapy , Muscular Atrophy/pathology , Disease Models, Animal , Magnetic Resonance Spectroscopy , Male , Muscle Proteins/metabolism , Muscular Disorders, Atrophic/metabolism , Muscular Disorders, Atrophic/drug therapy , Muscular Disorders, Atrophic/pathology , Ubiquitin-Protein Ligases/metabolism , Metabolome/drug effects , Hindlimb Suspension , Tripartite Motif Proteins/metabolism , Mice, Inbred C57BL , Myosin Heavy Chains/metabolism
15.
Cell Cycle ; : 1-20, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796716

ABSTRACT

This investigation examined the potential of ginsenoside Rg3 in addressing traumatic brain injury (TBI). A TBI mouse model underwent treatment with ginsenoside Rg3 and nicotinamide (NAM). Neurological and motor functions were assessed using modified neurological severity score and rotarod tests. Brain water content in mice was detected. Primary mouse microglia were exposed to lipopolysaccharide (LPS), ginsenoside Rg3, and NAM. Nissl and immunofluorescence staining were utilized to investigate hippocampal damage, and localization of P65, Iba1 and INOS in microglia. Hippocampal neurons were grown in a culture medium derived from microglia. CCK-8 and TUNEL assays were employed to evaluate the viability and apoptosis of hippocampal neurons. Proinflammatory factors and proteins were tested using ELISA, western blot and immunofluorescence staining. As a result, ginsenoside Rg3 enhanced neurological and motor functions in mice post-TBI, reduced brain water content, alleviated hippocampal neuronal neuroinflammation and damage, activated SIRT1, and deactivated the NF-kB pathway. In LPS-stimulated microglia, ginsenoside Rg3 diminished inflammation, activated SIRT1, deactivated the NF-kB pathway, and facilitated nuclear localization of P65 and co-localization of Iba1 and INOS. The effects of ginsenoside Rg3 were countered by NAM in both TBI mice and LPS-stimulated microglia. Hippocampal neurons cultured in a medium containing LPS, ginsenoside Rg3, and NAM-treated microglia showed improved viability and reduced apoptosis compared to those cultured in a medium with LPS and ginsenoside Rg3-treated microglia alone. Ginsenoside Rg3 was effective in reducing neuroinflammation and damage in hippocampal neurons following TBI by modulating the SIRT1/NF-kB pathway, suggesting its potential as a therapeutic agent for TBI.

16.
Appl Spectrosc ; : 37028241254391, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38772555

ABSTRACT

An infrared squaraine dye was utilized to detect Cu2+ in solvents based on H-aggregates of squaraine dye. H-aggregates are a type of aggregation with enhanced photophysical properties compared to monomers. In the presence of a Ca2+ solution, F-Cl offers exceptional H-aggregators that can be transformed into monomers by adding Cu2+. Furthermore, this mode successfully demonstrated fluorescence changes in HeLa cells cultured in vitro after the addition of Ca2+ or Cu2+. A highly specific detection of Cu2+ was achieved using this transformation mode.

17.
Sci Total Environ ; 935: 173456, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38788937

ABSTRACT

Cypermethrin (CYP), a synthetic pyrethroid pesticide, has been detected in agriculture and aquaculture. However, there is limited knowledge about the transgenerational impacts. This study aimed to investigate the developmental toxicity of CYP on F1 larvae offspring of adult zebrafish exposed to various CYP concentrations (5, 10, and 20 µg/L) for 28 days. The results indicated that CYP accumulated in parental zebrafish, and CYP was below the limit of quantification in offspring. Paternal exposure impacted the hatching rate and heart rate of the F1 generation. Furthermore, CYP significantly impacted the development of swim bladders in progeny and dysregulated the genes relevant to swim bladder development. The neutrophil migrated to the swim bladder. The mRNA levels of the inflammatory factors were also significantly elevated. According to network toxicology, PI3-AKT may be the signaling pathway for CYP-influenced bladder development. Subsequent molecular docking and Western blot analysis showed CYP affected the PI3-AKT signaling pathway. Notably, MK-2206, a specific Akt inhibitor, rescued the CYP-induced damage of swim bladder development in offspring. The present study highlights the potential risks of CYP on the development of offspring and lasting impact in aquatic environments.

18.
Redox Biol ; 73: 103183, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38759418

ABSTRACT

AIMS: Vascular calcification is strongly linked to the development of major adverse cardiovascular events, but effective treatments are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging category of oral hypoglycemic drugs that have displayed marked effects on metabolic and cardiovascular diseases, including recently reported vascular medial calcification. However, the roles and underlying mechanisms of SGLT2 inhibitors in vascular calcification have not been fully elucidated. Thus, we aimed to further determine whether SGLT2 inhibitors protect against vascular calcification and to investigate the mechanisms involved. METHODS AND RESULTS: A computed tomography angiography investigation of coronary arteries from 1554 patients with type 2 diabetes revealed that SGLT2 inhibitor use was correlated with a lower Agatston calcification score. In the vitamin D3 overdose, 5/6 nephrectomy chronic kidney disease-induced medial calcification and Western diet-induced atherosclerotic intimal calcification models, dapagliflozin (DAPA) substantially alleviated vascular calcification in the aorta. Furthermore, we showed that DAPA reduced vascular calcification via Runx2-dependent osteogenic transdifferentiation in vascular smooth muscle cells (VSMCs). Transcriptome profiling revealed that thioredoxin domain containing 5 (TXNDC5) was involved in the attenuation of vascular calcification by DAPA. Rescue experiments showed that DAPA-induced TXNDC5 downregulation in VSMCs blocked the protective effect on vascular calcification. Furthermore, TXNDC5 downregulation disrupted protein folding-dependent Runx2 stability and promoted subsequent proteasomal degradation. Moreover, DAPA downregulated TXNDC5 expression via amelioration of oxidative stress and ATF6-dependent endoplasmic reticulum stress. Consistently, the class effects of SGLT2 inhibitors on vascular calcification were validated with empagliflozin in intimal and medial calcification models. CONCLUSIONS: SGLT2 inhibitors ameliorate vascular calcification through blocking endoplasmic reticulum stress-dependent TXNDC5 upregulation and promoting subsequent Runx2 proteasomal degradation, suggesting that SGLT2 inhibitors are potentially beneficial for vascular calcification treatment and prevention.

19.
Phytochemistry ; 224: 114163, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815883

ABSTRACT

Stereochemical investigations on the twigs and leaves of Solanum erianthum afforded five pairs of lignanamide enantiomers and a previously undescribed phenolic amide (3). Particularly, two pairs of previously undescribed lignanamide racemates (1a/1b-2a/2b) represent the first case of natural products that feature an unreported 5/5-fused N/O-biheterocyclic core. Their structures, including the absolute configurations, were determined unambiguously by using spectroscopic analyses and electronic circular dichroism calculations. A speculative biogenetic pathway for 1-3 was proposed. Interestingly, these lignanamides exhibited enantioselective antiplasmodial activities against drug-sensitive Plasmodium falciparum 3D7 strain and chloroquine-resistant Plasmodium falciparum Dd2 strain, pointing out that chirality plays an important role in drug development.

20.
Adv Sci (Weinh) ; : e2403507, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38733084

ABSTRACT

The defects in perovskite film can cause charge carrier trapping which shortens carrier lifetime and diffusion length. So defects passivation has become promising for the perovskite studies. However, how defects disturb the carrier transport and how the passivating affects the carrier transport in CsPbBr3 are still unclear. Here the carrier dynamics and diffusion processes of CsPbBr3 and LiBr passivated CsPbBr3 films are investigated by using transient absorption spectroscopy and transient absorption microscopy. It's found that there is a fast hot carrier trapping process with the above bandgap excitation, and the hot carrier trapping would decrease the population of cold carriers which are diffusible, then lower the carrier diffusion constant. It's proved that LiBr can passivate the defect and lower the trapping probability of hot carriers, thus improve the carrier diffusion rate. The finding demonstrates the influence of hot carrier trapping to the carrier diffusion in CsPbBr3 film.

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