Discovery of Novel Imidazo[1,2-a]pyridine-Based HDAC6 Inhibitors as an Anticarcinogen with a Cardioprotective Effect.

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.

Novel biomarkers associated with oxidative stress and immune infiltration in intervertebral disc degeneration based on bioinformatics approaches.

BACKGROUND: The etiology of intervertebral disc degeneration (IVDD), a prevalent degenerative disease in the elderly, remains to be fully elucidated. The objective of this study was to identify immune infiltration and oxidative stress (OS) biomarkers in IVDD, aiming to provide further insights into the intricate pathogenesis of IVDD. METHODS: The Gene Expression microarrays were obtained from the Gene Expression Omnibus (GEO) database. We conducted enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. Subsequently, the R language packages CIBERSORT, MCPcounter, and WGCNA were employed to compare immune infiltration levels between IVDD samples and control samples. A protein-protein interaction (PPI) network was constructed using the Search Tools for the Retrieval of Interacting Genes (STRING) database to identify significant gene clusters. To identify hub genes, we employed Cytoscape's Molecular Complex Detection (MCODE) plug-in. The mRNA levels of hub genes in the cell model were validated by qPCR, while Western blotting was used to validate their protein levels. RESULTS: The GSE70362 dataset from the GEO database identified a total of 1799 genes that were differentially expressed. Among these, 43 genes were found to be differentially expressed and also associated with OS. The differentially expressed genes associated with OS and the immune-related module genes identified through WGCNA were further intersected, resulting in the identification of 10 key genes that were differentially expressed and played crucial roles in both immune response and OS. Subsequently, we validated four diagnostic markers (PPIA, MAP3K5, PXN, and JAK2) using the GSE122429 external dataset. In a cellular model of OS in NP cells, we have identified the upregulation of PPIA and PXN genes, which could serve as novel markers for IVDD. CONCLUSION: The study successfully identified and validated differentially expressed genes associated with oxidative stress and immune infiltration in IVDD samples compared to normal ones. Notably, the newly discovered biomarkers PPIA and PXN have not been previously reported in IVDD-related research.

Mechanistic Insights into Metabolic Function of Dynamin-Related Protein 1 (DRP1).

DRP1 plays crucial roles in mitochondrial and peroxisome fission. However, the mechanisms underlying the functional regulation of DRP1 in adipose tissue during obesity remain unclear. To elucidate the metabolic and pathological significance of diminished DRP1 in obese adipose tissue, we utilized adipose tissue-specific DRP1 KO mice challenged with an HFD. We observed significant metabolic dysregulations in the KO mice. Mechanistically, DRP1 exerts multifaceted functions in mitochondrial dynamics and ER-lipid droplet cross-talk in normal mice. Loss-of-function of DRP1 resulted in abnormally giant mitochondrial shapes, distorted mitochondrial membrane structure, and disrupted cristae architecture. Meanwhile, DRP1 deficiency induced the retention of nascent lipid droplets in ER, leading to perturbed overall lipid dynamics in the KO mice. Collectively, dysregulation of the dynamics of mitochondria, ER, and lipid droplets contributes to whole-body metabolic disorders, as evidenced by perturbations in energy metabolites. Our findings demonstrate that DRP1 plays a pivotal role in energy homeostasis in adipose tissue during obesity.

Microglia in the hypothalamic paraventricular nucleus sense hemodynamic disturbance and promote sympathetic excitation in hypertension.

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.

Risk factor analysis and nomogram construction of postoperative complications for patients with locally advanced gastric cancer who received neoadjuvant immunotherapy and chemotherapy.

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.

Characteristics and Cytological Analysis of Several Novel Allopolyploids and Aneuploids between Brassica oleracea and Raphanus sativus.

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.

The safety and efficacy of neoadjuvant PD-1 inhibitor plus chemotherapy for patients with locally advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitor for patients with locally advanced gastric cancer (LAGC). METHODS: An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT. RESULTS: After screening, 6 phase II/III randomized controlled trials (RCTs) and 9 retrospective studies with 2,953 patients were included. In meta-analysis, NICT group demonstrated a significantly higher rate of pathological complete response (pCR) (P<0.001) and R0 resection (P=0.001), and a lower 2-year recurrence rate (P=0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) (P=0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization. CONCLUSIONS: The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.

Exercise-Induced Central Fatigue: Biomarkers, and Non-Medicinal Interventions.

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.

Association between neutrophil to high-density lipoprotein cholesterol ratio (NHR) and depression symptoms among the United States adults: a cross-sectional study.

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.

Clinical features and genetic analysis of developmental and epileptic encephalopathy caused by biallelic variants of CACNA1B.

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.

A simulation study of irradiation effect on InAs/GaAsSb type II quantum dot structures.

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.

Relationships among perceived social support, mindful self-care, and resilience among a sample of nurses in three provinces in China: a cross-sectional study.

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.

Structural characterisation and optical properties of new alkaline earth phosphate CaMg(P4O12) and alkaline alumophosphate Cs3Al4(PO4)5.

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.

Protein-A immunoadsorption combined with immunosuppressive treatment in refractory primary Sjögren's syndrome coexisting with NMOSD: a case report and literature review.

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.

Hypercoagulable state and effect of low-molecular-weight heparin prophylaxis on coagulation after lung cancer resection: results from thrombo-elastography.

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.

Safety and efficacy of minimally invasive gastrectomy for older patients with gastric cancer after neoadjuvant chemotherapy and immunotherapy: a propensity score-matched analysis.

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).

The correlation between anti-phospholipase A2 receptor antibodies and hypercoagulability in patients with idiopathic membranous nephropathy.

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.

Deciphering the maize gene ZmGF14-3: implications for plant height based on co-expression networks.

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.

Droplet Impact on Superhydrophobic Mesh Surfaces.

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.

A Clinical-Radiomics Nomogram for Predicting Early Ischemic Stroke Risk in Patients with Transient Ischemic Attack.

OBJECTIVE: To develop and validate a clinical-radiomics nomogram for predicting early ischemic stroke risk in patients who sustain a transient ischemic attack (TIA). METHODS: A retrospective training dataset (n = 76) and a prospective validation dataset (n = 34) of patients with TIA were studied. Image processing was performed using ITK-snap and Artificial Intelligent Kit. Radiomics features were selected in R. A nomogram predicting recurrent TIA/stroke in 90 days as a recurrent ischemic event was established. Model performance was assessed by computing the receiver operating characteristic curve and decision curve analysis (DCA). RESULTS: We found a higher proportion of diabetes and hypertension in the patients with recurrent TIA compared with the stable patients in both the training and validation datasets (P < 0.05). Recurrent patients had significantly higher ABCD2 scores and plaque scores compared to stable patients. ABCD2 score and necrotic/lipid core area were independent risk factors for recurrent ischemic events (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.47-6.40; and OR, 1.20; 95% CI, 1.07-1.41, respectively). The radiomics model had area under the curve values of 0.737 (95% CI, 0.715-0.878) in the training dataset and 0.899 (95% CI, 0.706-0.936) in the validation dataset, which was superior to the ABCD2 score and plaque model for predicting stroke recurrence (P < 0.05). The nomogram predicting recurrent ischemic events was 0.923 (95% CI, 0.895-0.978) in the training dataset and 0.935 (95% CI, 0.830-0.959) in the validation dataset. DCA confirmed the clinical value of this nomogram. CONCLUSIONS: The nomogram, based on clinical ABCD2 score, carotid plaque components and radiomics score, shows good performance in predicting the risk of recurrent ischemic events in patients with TIA.