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Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.
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Introduction: The combination of neoadjuvant immunotherapy and chemotherapy (NICT) has become a common treatment regimen for locally advanced gastric cancer (LAGC). However, the safety and efficacy of radical gastrectomy following NICT (NICT-G) remain controversial. This study aimed to analyze the risk factors influencing postoperative complications (POCs) after NICT-G. Additionally, it aimed to construct a nomogram to provide a clinical reference for predicting POCs. Methods: This study included 177 patients who received NICT-G at the Chinese PLA General Hospital First Medical Center from January 2020 to January 2024. Univariable and multivariable logistic regression models were used to evaluate the risk factors influencing POCs, and a nomogram model was constructed. To evaluate the discrimination and accuracy of the nomogram model, the area under the receiver operating characteristic curve (AUC) and the calibration curve were measured. Results: In 177 patients who received NICT-G, the pathological complete response and major pathological response rates were 15.8% and 45.2%, respectively, whereas the rates of the overall and severe treatment-related adverse events were 71.8% and 15.8%, respectively. In addition, 43 (24.3%) patients developed overall POCs (Clavien-Dindo classification ≥ II). Univariable and multivariable logistic analyses showed that age ≥70 years, greater estimated blood loss, platelet/lymphocyte ratio (PLR) ≤196, neutrophil/lymphocyte ratio (NLR) >1.33, non-R0 resection, and body mass index (BMI) < 18.5 kg/m2 were independent risk factors for overall POCs (p < 0.05). The nomogram model developed using the abovementioned variables showed that the AUC (95% confidence interval [CI]) was 0.808 (95% CI): 0.731-0.885 in predicting the POC risk. The calibration curves showed that the prediction curve of the nomogram was a good fit for the actual POCs (Hosmer-Lemeshow test: χ2 = 5.76, P = 0.451). Conclusion: The independent risk factors for overall POCs in the NICT-G were age ≥ 70 years, greater estimated blood loss, PLR ≤ 196, NLR > 1.33, non-R0 resection, and BMI < 18.5 kg/m2. The nomogram model developed based on the abovementioned indicators showed better accuracy in predicting the POC risk.
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Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y12 receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.
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Polyploids are essential in plant evolution and species formation, providing a rich genetic reservoir and increasing species diversity. Complex polyploids with higher ploidy levels often have a dosage effect on the phenotype, which can be highly detrimental to gametes, making them rare. In this study, offspring plants resulting from an autoallotetraploid (RRRC) derived from the interspecific hybridization between allotetraploid Raphanobrassica (RRCC, 2n = 36) and diploid radish (RR, 2n = 18) were obtained. Fluorescence in situ hybridization (FISH) using C-genome-specific repeats as probes revealed two main genome configurations in these offspring plants: RRRCC (2n = 43, 44, 45) and RRRRCC (2n = 54, 55), showing more complex genome configurations and higher ploidy levels compared to the parental plants. These offspring plants exhibited extensive variation in phenotypic characteristics, including leaf type and flower type and color, as well as seed and pollen fertility. Analysis of chromosome behavior showed that homoeologous chromosome pairing events are widely observed at the diakinesis stage in the pollen mother cells (PMCs) of these allopolyploids, with a range of 58.73% to 78.33%. Moreover, the unreduced C subgenome at meiosis anaphase II in PMCs was observed, which provides compelling evidence for the formation of complex allopolyploid offspring. These complex allopolyploids serve as valuable genetic resources for further analysis and contribute to our understanding of the mechanisms underlying the formation of complex allopolyploids.
Subject(s)
Aneuploidy , Chromosomes, Plant , Polyploidy , Raphanus , Raphanus/genetics , Chromosomes, Plant/genetics , In Situ Hybridization, Fluorescence , Brassica/genetics , Hybridization, Genetic , Meiosis/genetics , Genome, Plant , Pollen/genetics , PhenotypeABSTRACT
BACKGROUND: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN. METHODS: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed. RESULTS: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value. CONCLUSION: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.
Subject(s)
Autoantibodies , Glomerulonephritis, Membranous , Receptors, Phospholipase A2 , Thrombophilia , Humans , Receptors, Phospholipase A2/immunology , Glomerulonephritis, Membranous/blood , Glomerulonephritis, Membranous/immunology , Glomerulonephritis, Membranous/complications , Male , Female , Retrospective Studies , Middle Aged , Adult , Thrombophilia/etiology , Thrombophilia/immunology , Thrombophilia/blood , Autoantibodies/bloodABSTRACT
BACKGROUND: Depression acts as a noteworthy worldwide public health challenge. Identifying accessible biomarkers is crucial for early diagnosis and intervention. The relationship between depression in adult Americans and the neutrophil to high-density lipoprotein cholesterol ratio (NHR) was investigated in this research. METHODS: The relationship between NHR and depressive symptoms was analyzed utilizing National Health and Nutrition Examination Survey data from 2005 to 2018 and the Patient Health Questionnaire-9. The study included 33,871 participants with complete NHR and depression data. Adjusted multivariable logistic regression models were used to account for possible confounders, and subgroup analyses were conducted to investigate effect changes. RESULTS: Elevated NHR levels were positively correlated with a heightened risk of depression (OR = 1.03, 95% CI: 1.01-1.05, P < 0.0005). After the NHR was divided into tertiles, those in the top tertile had an 18% higher chance of developing depression than those in the bottom tertile (OR = 1.18; 95% CI: 1.05-1.32; P for trend = 0.0041). Subgroup analyses revealed variations in this association based on race and marital status. Additionally, the relationship between NHR and depression demonstrated a U-shaped pattern, with a significant breakpoint identified at an NHR of 6.97. CONCLUSION: These results imply that the NHR may be a potential biomarker for depression risk, with implications for early detection and personalized treatment. Further research is needed to elucidate the mechanisms underlying the NHR-depression link and establish causality.
Subject(s)
Cholesterol, HDL , Depression , Neutrophils , Humans , Male , Depression/blood , Depression/epidemiology , Female , Cholesterol, HDL/blood , Adult , Cross-Sectional Studies , Middle Aged , United States/epidemiology , Neutrophils/metabolism , Nutrition Surveys , Biomarkers/blood , Risk Factors , Aged , Logistic ModelsABSTRACT
Objective: To analyze the clinical features and genetic etiology of a patient with developmental and epileptic encephalopathy. Methods: The clinical information and peripheral blood of the patient and their family members were collected before the whole exome sequencing analysis was performed and Sanger sequencing was employed to verify the potential variant. Results: The patient presented with epilepsy and cerebral palsy with his parents, brother, and sister being all healthy. Whole exome sequencing analysis revealed that the child carried the paternal c.823del (p. R275Gfs*31) heterozygous variant and the maternal c.2456del (p.V819Gfs*190) heterozygous variant of the CACNA1B gene. Pedigree verification found that the elder brother and amniotic fluid of fetus in womb carried the paternal c.823del heterozygous variant, and the elder sister carried the maternal c.2456del heterozygous variant, which conformed to the law of autosomal recessive inheritance. Neither of these two variants has been reported in the literature and has not been included in the Genomic Mutation Frequency Database (gnomAD); according to the American Academy of Medical Genetics and Genomics Variation Grading Guidelines (ACMG), both variants are classified as pathogenic variants (PVS1+PM2-Supporting + PM3). Conclusion: This study reported the first case of a child with neurodevelopmental disorder and epilepsy caused by a new compound heterozygous variant of the CACNA1B gene in China, clarified its genetic etiology, enriched the mutation spectrum and disease spectrum of CACNA1B gene, and provided a basis for prenatal diagnosis of the family.
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Fatigue, commonly experienced in daily life, is a feeling of extreme tiredness, shortage or lack of energy, exhaustion, and difficulty in performing voluntary tasks. Central fatigue, defined as a progressive failure to voluntarily activate the muscle, is typically linked to moderate- or light-intensity exercise. However, in some instances, high-intensity exercise can also trigger the onset of central fatigue. Exercise-induced central fatigue often precedes the decline in physical performance in well-trained athletes. This leads to a reduction in nerve impulses, decreased neuronal excitability, and an imbalance in brain homeostasis, all of which can adversely impact an athlete's performance and the longevity of their sports career. Therefore, implementing strategies to delay the onset of exercise-induced central fatigue is vital for enhancing athletic performance and safeguarding athletes from the debilitating effects of fatigue. In this review, we discuss the structural basis, measurement methods, and biomarkers of exercise-induced central fatigue. Furthermore, we propose non-pharmacological interventions to mitigate its effects, which can potentially foster improvements in athletes' performances in a healthful and sustainable manner.
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The evolutionary analysis showed that the GF14 family was conserved, however, there was limited evidence linking GF14s to plant height. In our investigations, we discovered a co-expression relationship between ZmGF14s and functionally characterized genes linked to plant height. In the co-expression network, we identified ZmGF14-3, a gene expression exhibiting a positive correlation with plant height in three maize varieties, we postulated that this gene could be intimately linked to plant height development. Subsequently, we cloned ZmGF14-3 from the maize B73 inbred line and overexpressed it in Arabidopsis, resulting in markedly dwarfed transgenic phenotypes. Measurements of endogenous phytohormones disclosed a significant reduction in concentrations of Gibberellic Acid 7 (GA7) and Indole-3-Acetic Acid (IAA) in the overexpressed Arabidopsis, furthermore, qPCR results highlighted a pronounced decrease in the expression levels of plant height-related genes when compared to the wild type, therefore, it is plausible to posit that ZmGF14-3 plays a pivotal role in regulating the growth and development of maize through interactions with various phytohormone-related genes. Thus, delving into the potential interactions between ZmGF14-3 and these genes holds the promise of yielding valuable insights into the molecular mechanisms underpinning plant height development in maize.
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Inflammasomes are sensors that detect cytosolic microbial molecules or cellular damage, and in response they initiate a form of lytic regulated cell death called pyroptosis. Inflammasomes signal via homotypic protein-protein interactions where CARD or PYD domains are crucial for recruiting downstream partners. Here, we screened these domains from NLR family proteins, and found that the PYD domain of NLRP6 and NLRP12 could activate caspase-1 to induce cleavage of IL-1ß and GSDMD. Inflammasome reconstitution verified that full length NLRP6 and NLRP12 formed inflammasomes in vitro, and NLRP6 was more prone to auto-activation. NLRP6 was highly expressed in intestinal epithelial cells (IEC), but not in immune cells. Molecular phylogeny analysis found that NLRP12 was closely related to NLRP3, but the activation mechanisms are different. NLRP3 was highly expressed in monocytes and macrophages, and was modestly but appreciably expressed in neutrophils. In contrast, NLRP12 was specifically expressed in neutrophils and eosinophils, but was not detectable in macrophages. NLRP12 mutations cause a periodic fever syndrome called NLRP12 autoinflammatory disease. We found that several of these patient mutations caused spontaneous activation of caspase-1 in vitro, which likely causes their autoinflammatory disease. Different cell types have unique cellular physiology and structures which could be perturbed by a pathogen, necessitating expression of distinct inflammasome sensors to monitor for signs of infection.
Subject(s)
Apoptosis Regulatory Proteins , Inflammasomes , Intracellular Signaling Peptides and Proteins , NLR Family, Pyrin Domain-Containing 3 Protein , Inflammasomes/metabolism , Humans , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Animals , HEK293 CellsABSTRACT
The treatment of primary Sjögren's syndrome (pSS) coexisting with neuromyelitis optica spectrum disorder (NMOSD) using protein-A immunoadsorption combined with immunosuppressive therapy has rarely been reported. Herein, we present the case of a 35-year-old female diagnosed with pSS concomitant with NMOSD (pSS-NMOSD) who demonstrated a positive response to protein-A immunoadsorption after failing to respond to therapy comprising high-dose intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG). Within one week of receiving three sessions of immunoadsorption combined with immunosuppressive treatment, the patient's clinical symptoms (blurred vision, paraparesis, and dysfunctional proprioception) significantly improved. Additionally, a rapid decrease in the circulating levels of Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG), immunoglobulin (Ig) A, IgG, IgM, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were observed. Magnetic resonance imaging (MRI) further revealed a significant reduction in the lesions associated with longitudinal extensive transverse myelitis. During the follow-up period, prednisolone was gradually tapered to a maintenance dose of 5-10 mg/day, whereas mycophenolate mofetil (MMF) was maintained at 1.0-1.5 g/day. The patient's condition has remained stable for four years, with no signs of recurrence or progression observed on imaging examination. Therefore, this case suggests that protein A immunoadsorption may represent a potentially effective therapeutic option for patients with pSS-NMOSD who are refractory to conventional treatments.
Subject(s)
Immunosuppressive Agents , Neuromyelitis Optica , Sjogren's Syndrome , Humans , Female , Neuromyelitis Optica/therapy , Neuromyelitis Optica/immunology , Neuromyelitis Optica/diagnosis , Sjogren's Syndrome/therapy , Sjogren's Syndrome/immunology , Sjogren's Syndrome/complications , Sjogren's Syndrome/diagnosis , Adult , Immunosuppressive Agents/therapeutic use , Staphylococcal Protein A/immunology , Autoantibodies/blood , Autoantibodies/immunology , Treatment Outcome , Immunosorbent Techniques , Aquaporin 4/immunology , Combined Modality TherapyABSTRACT
BACKGROUND: Lung cancer patients undergoing surgery are at increased risk for Venous thromboembolism (VTE). We monitored changes in perioperative coagulation status through Thrombo-elastography (TEG), and monitored the anticoagulant effect of low molecular weight heparin through TEG for the first time. METHODS: From July 2019 to January 2020, 207 patients receiving curative surgery were retrospectively screened. and 23 patients were excluded because they did not meet the inclusion criteria. Blood samples were required at three time points (prior to, the first and third day after surgery). Some patients were administrated nadroparin calcium daily from the first day after surgery. Repeated measures ANOVA and Chi-square test were used to analyze the coagulation states variation. To balance the confounders, propensity score matching (PSM) was used to determine the differences of coagulation states between patients with or without Low-molecular-weight heparin (LMWH) prophylaxis. RESULTS: In 184 patients, TEG parameters displayed significant procoagulant changes after lung surgery but conventional coagulation tests exhibited paradoxical trends. There were 6.5% (12/184) of patients identified as hypercoagulability before surgery. According to TEG results, the proportion of patients with hypercoagulability rose from 21.7% to 25% postoperatively, but more were classified into platelet or mixed hypercoagulability at third day compared with that at first day (3.8% vs 14.1%, P < 0.001). By PSM analysis, there were no significant differences in the proportion of hypercoagulable patients postoperatively between chemoprophylactic and nonprophylactic group. CONCLUSIONS: TEG was eligible to distinguish changing states of hypercoagulability postoperatively and indicate the role of platelet in blood hypercoagulability. Administration of postoperative LMWH prophylaxis showed little mitigation on hypercoagulable states.
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The research aims to study the therapeutic impact of HEK293-XPack-Olig2 cell-derived exosomes on remyelination of the corpus callosum in a cuprizone-induced demyelinating disease model. A lentiviral vector expressing Olig2 was constructed using XPack technology. The highly abundant Olig2 exosomes (ExoOs) were isolated by centrifugation for subsequent experiments. Western blot, nanoparticle tracking analysis (NTA), and electron microscopy showed no significant difference in particle size and morphology between Exos and ExoOs, and a high level of Olig2 expression could be detected in ExoOs, indicating that exosome modification by XPack technology was successful. The Black Gold/Fluromyelin staining analysis showed that the ExoOs group significantly reduced the demyelination area in the corpus callosum compared to the PBS and Exos groups. Additionally, the PDGFRα/APC staining of the demyelinating region revealed an increase in APC+ oligodendrocytes and a decrease in PDGFRα+ oligodendrocyte progenitor cells (OPCs) in the ExoOs group. Furthermore, there was evident myelin regeneration in the demyelinated areas after ExoOs treatment, with better g-ratio and a higher number of intact myelin compared to the other treatment groups. The level of Sox10 expression in the brain tissue of the ExoOs group were higher compared to those of the PBS and Exos groups. The demyelination process can be significantly slowed down by the XPack-modified exosomes, the differentiation of OPCs promoted, and myelin regeneration accelerated under pathological conditions. This process is presumed to be achieved by changing the expression level of intracellular differentiation-related genes after exosomes transport Olig2 enriched into oligodendrocyte progenitors.
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Two new family members of mixed alkali-earth metal phosphate and aluminophosphate CaMg(P4O12) and Cs3Al4(PO4)5 were prepared from a phosphate system using a high-temperature solution method. The structural analysis results show that two compounds crystallize in the monoclinic space group C2/c and P21/n and feature a three-dimensional (3D) network. The 3D structure of CaMg(P4O12) consists of [CaO6], [MgO6] octahedra and [P4O12] rings, in which the [MgO6] and [P4O12] rings link to form a 3D structure and Ca2+ cations are filled within the structure. Interestingly, for compound Cs3Al4(PO4)5, its structure features 4, 8, and 12-ring channels with [Al2O4O4P2O4], [Al4O8O8P4O8] and [Al6O12O12P6O12] units as BBUs, respectively; the Cs+ cations are located in the cavities. Furthermore, IR spectral analysis and thermal properties are discussed. UV-vis-NIR diffuse reflectance spectroscopy data show that the UV cutoff edges of CaMg(P4O12) are below 200 nm. Remarkably, in order to determine optical properties and the structure-properties relationship, theoretical calculations were adopted. Electronic structure calculations demonstrate that CaMg(P4O12) has an indirect band gap with the value of 5.86 eV, and Cs3Al4(PO4)5 has a direct band gap of 5.21 eV.
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Ammonia is a gas that produces zero carbon emissions when used in energy storage systems. Hence, there is increasing interest for the application of ammonia as fuel in various energy storage devices, specifically solid oxide fuel cells (SOFCs), as it has the potential to be efficient and environmentally friendly. In addition, compared to other fuel cells, SOFCs fed with ammonia offer various benefits such as such as sustainability and safety. This review compares and contrasts the opportunities and challenges of ammonia fuel cell technologies and helps to analyze their working principles. The main goal of this review is to investigate the viability of an "all-protonic" fuel cell using ammonia fuel while also highlighting the key challenges and limitations of implementing such technology.
Subject(s)
Ammonia , Ammonia/chemistry , Electric Power SuppliesABSTRACT
This study elucidates the molecular mechanisms by which FABP3 regulates neuronal apoptosis via mitochondrial autophagy in the context of cerebral ischemia-reperfusion (I/R). Employing a transient mouse model of middle cerebral artery occlusion (MCAO) established using the filament method, brain tissue samples were procured from I/R mice. High-throughput transcriptome sequencing on the Illumina CN500 platform was performed to identify differentially expressed mRNAs. Critical genes were selected by intersecting I/R-related genes from the GeneCards database with the differentially expressed mRNAs. The in vivo mechanism was explored by infecting I/R mice with lentivirus. Brain tissue injury, infarct volume ratio in the ischemic penumbra, neurologic deficits, behavioral abilities, neuronal apoptosis, apoptotic factors, inflammatory factors, and lipid peroxidation markers were assessed using H&E staining, TTC staining, Longa scoring, rotation experiments, immunofluorescence staining, and Western blot. For in vitro validation, an OGD/R model was established using primary neuron cells. Cell viability, apoptosis rate, mitochondrial oxidative stress, morphology, autophagosome formation, membrane potential, LC3 protein levels, and colocalization of autophagosomes and mitochondria were evaluated using MTT assay, LDH release assay, flow cytometry, ROS/MDA/GSH-Px measurement, transmission electron microscopy, MitoTracker staining, JC-1 method, Western blot, and immunofluorescence staining. FABP3 was identified as a critical gene in I/R through integrated transcriptome sequencing and bioinformatics analysis. In vivo experiments revealed that FABP3 silencing mitigated brain tissue damage, reduced infarct volume ratio, improved neurologic deficits, restored behavioral abilities, and attenuated neuronal apoptosis, inflammation, and mitochondrial oxidative stress in I/R mice. In vitro experiments demonstrated that FABP3 silencing restored OGD/R cell viability, reduced neuronal apoptosis, and decreased mitochondrial oxidative stress. Moreover, FABP3 induced mitochondrial autophagy through ROS, which was inhibited by the free radical scavenger NAC. Blocking mitochondrial autophagy with sh-ATG5 lentivirus confirmed that FABP3 induces mitochondrial dysfunction and neuronal apoptosis by activating mitochondrial autophagy. In conclusion, FABP3 activates mitochondrial autophagy through ROS, leading to mitochondrial dysfunction and neuronal apoptosis, thereby promoting cerebral ischemia-reperfusion injury.
Subject(s)
Apoptosis , Autophagy , Fatty Acid Binding Protein 3 , Mitochondria , Neurons , Reperfusion Injury , Animals , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Apoptosis/physiology , Autophagy/physiology , Neurons/metabolism , Neurons/pathology , Mice , Mitochondria/metabolism , Male , Fatty Acid Binding Protein 3/metabolism , Fatty Acid Binding Protein 3/genetics , Mice, Inbred C57BL , Infarction, Middle Cerebral Artery/pathology , Infarction, Middle Cerebral Artery/metabolism , Brain Ischemia/metabolism , Brain Ischemia/pathology , Oxidative Stress/physiologyABSTRACT
BACKGROUND: The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) in older patients with gastric cancer remains controversial. This study aimed to evaluate the safety, and efficacy of MIG for older patients who underwent neoadjuvant chemotherapy and immunotherapy (NICT). METHODS: The clinical data of 726 older patients aged over 65 years who underwent upfront MIG or MIG after NICT in the Department of General Surgery, Chinese PLA General Hospital First Medical Center between Jan 2020 and Nov 2023 were retrospectively analyzed. Propensity score-matched (PSM) analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables, short- and long-term outcomes were compared between the two groups. RESULTS: The baseline characteristics were comparable between 61 patients in the NICT-MIG group and 114 patients in the MIG group after PSM (P > 0.05). The major pathological response (MPR) rate and pathological complete response (pCR) rate were 44.2% and 21.3%, respectively, in the NICT-MIG group. Patients in the NICT-MIG group had longer operation times (P = 0.005) and postoperative days (P = 0.030) than those in the MIG group. No significant differences were found in intraoperative bleeding, number of retrieved lymph nodes, first flatus day, R0 resection rate, overall postoperative complication (POC) morbidity, severe POC morbidity, 2-year overall, and recurrence-free survival between the MIG and NICT-MIG groups (P > 0.05). Multivariate logistic analysis revealed that an estimated blood loss > 200 mL (P = 0.010) and a lymphocyte-to-monocyte ratio (LMR) ≤ 3.25 (P = 0.006) were independent risk factors for POCs after MIG in older patients. CONCLUSION: The safety, and efficacy of NICT-MIG were comparable to those of upfront MIG in older patients with GC. Patients with an estimated blood loss > 200 mL or an LMR ≤ 3.25 should be carefully evaluated for an increased risk of POCs in older patients who undergo MIG. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number: ChiCTR2400086827).
Subject(s)
Gastrectomy , Immunotherapy , Neoadjuvant Therapy , Propensity Score , Stomach Neoplasms , Humans , Stomach Neoplasms/therapy , Stomach Neoplasms/surgery , Gastrectomy/methods , Male , Female , Aged , Neoadjuvant Therapy/methods , Retrospective Studies , Immunotherapy/methods , Minimally Invasive Surgical Procedures/methods , Treatment Outcome , Aged, 80 and overABSTRACT
Particles in space cause irradiation damage to the solar cells (SCs), resulting in the degradation of their performance. Quantum dot solar cells (QDSCs) have higher theoretical efficiency and better irradiation resistance than the conventional GaAs SCs, which makes them highly promising for application in space. In this paper, we study the proton irradiation effect on InAs/GaAs0.8Sb0.2 QDSCs by SRIM program. The simulation result shows that the InAs/GaAs0.8Sb0.2 QDSCs have fewer vacancies than GaAs SCs when irradiated with low-energy proton, which indicates that the InAs/GaAs0.8Sb0.2 QDSCs have better anti-irradiation characteristics. The study about displacements per atom and proton concentration in two SCs shows that protons with low energy and high irradiation fluences will cause more serious damage in InAs/GaAs0.8Sb0.2 QDSCs. In addition, the proton incident angle affects the vacancy distribution, while the number of QD layers has little effect on it.
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Objective: In this study, we aimed to determine the relationships among perceived social support, mindful self-care, and resilience in a sample of nurses in three provinces of China. Methods: A cross-sectional study was conducted in seven hospitals in Guangdong, Guizhou, and Henan provinces between August and October, 2023; the provinces are located in south, southwest, and central China. A total of 389 nurses were surveyed using a self-designed sociodemographic characteristics questionnaire and the Chinese versions of Multidimensional Scale of the Perceived Social Support, Brief-Mindful Self-Care Scale and the 10-item Connor-Davidson Resilience Scale (CD-RISC-10). Results: Of the 389 nurses, the majority were women (n = 365; 93.8%), aged 26-35 years (n = 244; 62.7%) and had bachelor's degrees (n = 337; 86.6%), had worked for 10-20 years (n = 136; 35%), with junior professional titles (n = 331; 85.1%), and had a monthly income in the range 3,001-6,000 yuan in CNY (n = 239; 61.4%). Nurses' resilience was measured using the CD-RISC-10, which ranges from 10 to 40 points. And average score of nurses' resilience was (23.94 ± 6.95). Multiple linear regression showed that scores for resilience were higher among nurses who had higher educational attainment (95% confidence interval: 0.568-3.024, p < 0.01), professional titles (95% confidence interval: 0.009-1.693, p < 0.05), scores of mindful self-care (95% confidence interval: 0.086-0.155, p < 0.01), and scores of perceived social support (95% confidence interval: 0.242-0.328, p < 0.01). Conclusion: Nurses with higher educational attainment and professional titles exhibited higher levels of resilience. Perceived social support and mindfulness self-care are significantly positively correlated with resilience of nurses. The findings of this study are beneficial to further our understanding of nurses' resilience. The identification of associated factors is conducive to providing more support for nurses who tend to have lower resilience earlier, and can provide useful information for research targeted intervention and support plans aimed at improving nurses' resilience in the future.
Subject(s)
Mindfulness , Resilience, Psychological , Self Care , Social Support , Humans , Cross-Sectional Studies , Female , China , Adult , Male , Surveys and Questionnaires , Nurses/psychology , Nurses/statistics & numerical data , Middle AgedABSTRACT
Reducing the contact time of droplet impacts on surfaces is crucial for various applications including corrosion prevention and anti-icing. This study aims to explore a novel strategy that greatly reduces contact time using a superhydrophobic mesh surface with multiple sets of mutually perpendicular ridges while minimizing the influence of the impacting location. The effects of the impact Weber numbers and ridge spacing on the characteristics of the impact dynamics and contact time are studied experimentally. The experimental results reveal that, for the droplet impact on mesh surfaces, ridges can segment the liquid film into independently multiple-retracting liquid subunits. The retracted subunits provide the upward driving force, which may promote the splashing or pancake bouncing of droplets. At this point, the contact time has a negligible sensitivity for the impacting position and is significantly reduced by up to 68%. Furthermore, the time, dynamic pressure, and energy criteria for triggering splashing and pancake bouncing are proposed theoretically. This work provides an understanding of the mechanism and the design guidelines for effectively reducing the contact time of the impacting droplet on superhydrophobic surfaces.