Safety and effectiveness of the sutureless integrated stented graft prosthesis in an animal model.

Background: Prolonged circulatory arrest time is an independent risk factor for postoperative adverse events of type A aortic dissection (TAAD) surgery. Further reduction of the circulatory arrest time is essential to improve surgical outcomes. This study aimed to evaluate the safety and effectiveness of the novel Sutureless Integrated Stented (SIS) graft prosthesis in an animal experiment. Materials and methods: Straight type of the SIS graft prosthesis was implanted into the descending aorta of 10 adult male sheep, and the use of the device was scored on a scale of 1-10. Aortic digital subtraction angiography (DSA) was performed at 4, 14, and 26 weeks to investigate the prostheses. After 26 weeks, the animals were sacrificed for histological analysis. Results: The immediate success rate of the surgery was 100 %, and the overall mean score of the use of the device was 9.65 ± 0.99. Three animals died from non-device-related causes during follow-up. Aortic DSA showed filling defects in 5 animals. Histological analysis revealed that all prostheses were intact. Except for 2 early deaths, the other 8 prostheses were endothelialized with mild inflammation, foreign body reactions, and intimal fibrosis. The mean cross-sectional area of the sutureless region was reduced by 26.4 % (range, 1.3-39.1 %). Conclusions: The safety and effectiveness of the novel SIS graft prosthesis were acceptable, and the delivery system exhibited a promising performance. Using the SIS graft prosthesis in TAAD surgery was expected to simplify the procedures and shorten the circulatory arrest time. Further large-scale clinical trials are required to verify these findings.

Applicability of STOPP/START prescribing criteria in integrated Swedish administrative health registries and a Swedish population-based cohort.

PURPOSE: The STOPP/START criteria are frequently applied in observational studies to assess potentially inappropriate prescribing in older adults. This study aimed to assess the applicability of the three available STOPP/START versions in two distinct data sources. METHODS: To evaluate the applicability of the three versions of STOPP/START criteria, we used two observational data sources: (i) Integrated Swedish administrative health registries (ISHR) encompassing routinely collected health data and (ii) the population-based Swedish National study on Aging and Care in Kungsholmen (SNAC-K), based on health professional-led clinical assessments. The Anatomical Therapeutic Classification code (ATC) was used to categorise medications. Diseases were categorised using the international classification of diseases version 10 (ICD10). RESULTS: The first STOPP/START version demonstrated an applicability rate of 80% in ISHR and 84% in SNAC-K. The second version demonstrated an applicability of 64% in ISHR and 74% in SNAC-K. The third version showed an applicability of 66% in ISHR and 77% in SNAC-K. Challenges in applicability included broad definitions, vague terminology, and the lack of information on disease severity, symptomatic traits, and stability of certain conditions. CONCLUSION: The applicability of the STOPP/START criteria in observational studies seems to have decreased in more recent versions of the tool. Population-based studies with comprehensive clinical assessments may offer higher applicability compared to studies based on administrative data. Future versions of the STOPP/START criteria should prioritise clear and unambiguous definitions to improve their applicability in research and promote result generalisability and comparability.

Identification of new microtubule small-molecule inhibitors and microtubule-associated genes against triple negative breast cancer.

Breast cancer represents the leading cancer type and leading cause of cancer-related death among women in the world. Triple-negative breast cancer (TNBC) is a subset of breast cancer with the poorest prognosis and still lacking of effective therapeutic options. We recently screened a natural product library and identified 3 new hit compounds with selective and prominent anti-TNBC activities on different subtype of TNBC cell lines. Interestingly, all of these 3 hit compounds belong to "cytoskeletal drugs" that target tubulin and microtubule function. Our data also showed that these hit compounds showed consistently effective on TNBC cells which are resistant to those currently used antimicrotubule agents such as Paclitaxel. RNA-Sequencing analyses revealed the anti-TNBC mechanisms of these hit compounds and identified a subset of new cellular factors commonly affected by hit compounds in different subtypes of TNBC cells. Among them, we demonstrated AHCYL1 and SPG21 as new microtubule-associated proteins, which were required for TNBC cell survival with clinical implication through tissue array analysis. Our studies provide new insights into the mechanisms of TNBC pathogenesis and offer promising therapeutic directions for this aggressive breast cancer.

Cryo-EM structure of the human Asc-1 transporter complex.

The Alanine-Serine-Cysteine transporter 1 (Asc-1 or SLC7A10) forms a crucial heterodimeric transporter complex with 4F2hc (SLC3A2) through a covalent disulfide bridge. This complex enables the sodium-independent transport of small neutral amino acids, including L-Alanine (L-Ala), Glycine (Gly), and D-Serine (D-Ser), within the central nervous system (CNS). D-Ser and Gly are two key endogenous glutamate co-agonists that activate N-methyl-d-aspartate (NMDA) receptors by binding to the allosteric site. Mice deficient in Asc-1 display severe symptoms such as tremors, ataxia, and seizures, leading to early postnatal death. Despite its physiological importance, the functional mechanism of the Asc-1-4F2hc complex has remained elusive. Here, we present cryo-electron microscopy (cryo-EM) structures of the human Asc-1-4F2hc complex in its apo state, D-Ser bound state, and L-Ala bound state, resolved at 3.6 Å, 3.5 Å, and 3.4 Å, respectively. Through detailed structural analysis and transport assays, we uncover a comprehensive alternating access mechanism that underlies conformational changes in the complex. In summary, our findings reveal the architecture of the Asc-1 and 4F2hc complex and provide valuable insights into substrate recognition and the functional cycle of this essential transporter complex.

Cryo-EM structures of the human NaS1 and NaDC1 transporters revealed the elevator transport and allosteric regulation mechanism.

The solute carrier 13 (SLC13) family comprises electrogenic sodium ion-coupled anion cotransporters, segregating into sodium ion-sulfate cotransporters (NaSs) and sodium ion-di- and-tricarboxylate cotransporters (NaDCs). NaS1 and NaDC1 regulate sulfate homeostasis and oxidative metabolism, respectively. NaS1 deficiency affects murine growth and fertility, while NaDC1 affects urinary citrate and calcium nephrolithiasis. Despite their importance, the mechanisms of substrate recognition and transport remain insufficiently characterized. In this study, we determined the cryo-electron microscopy structures of human NaS1, capturing inward-facing and combined inward-facing/outward-facing conformations within a dimer both in apo and sulfate-bound states. In addition, we elucidated NaDC1's outward-facing conformation, encompassing apo, citrate-bound, and N-(p-amylcinnamoyl) anthranilic acid (ACA) inhibitor-bound states. Structural scrutiny illuminates a detailed elevator mechanism driving conformational changes. Notably, the ACA inhibitor unexpectedly binds primarily anchored by transmembrane 2 (TM2), Loop 10, TM11, and TM6a proximate to the cytosolic membrane. Our findings provide crucial insights into SLC13 transport mechanisms, paving the way for future drug design.

Development and validation of a model for predicting the risk of cardiovascular events in maintenance hemodialysis patients.

The mortality rates for patients undergoing hemodialysis (HD) remain unacceptably high compared to the general population, and more specific information about the causes of death is not known. The study aimed to develop and validate a risk prediction model that uses common clinical factors to predict the probability of cardiovascular events in maintenance hemodialysis (MHD) patients. The study involved 3488 adult patients who received regular scheduled hemodialysis treatment at 20 hemodialysis centers in southwest China between June 2015 and August 2020, with follow-up until August 2021. The optimal parameter set was identified by multivariable Cox regression analyses and Cross-LASSO regression analyses and was used to establish a nomogram for predicting the risk of cardiovascular events in maintenance hemodialysis patients at 3 and 5 years. The performance of the model was evaluated using the consistency index (Harrell's C-index), the area under the receiver operating characteristic (ROC) curve, and calibration plots. The model was validated by tenfold cross-validation and bootstrapping with 1000 resamples. In the derivation cohort, the model yields an AUC of 0.764 [95% confidence interval (CI), 0.737-0.790] and 0.793 [CI, 0.757-0.829] for predicting the risk of cardiovascular events of MHD patients at 3 and 5 years. In the internal validation cohort AUC of 0.803 [95% CI, 0.756-0.849], AUC of 0.766 [95% CI, 0.686-0.846], and the external validation cohort AUC of 0.826 [95% CI, 0.765-0.888], AUC of 0.817 [95% CI, 0.745-0.889] at 3 and 5 years. The model's calibration curve is close to the ideal diagonal. By tenfold cross-validation analyses, the 3- and 5-year risk of cardiovascular events (AUC 0.732 and 0.771, respectively). By the bootstrap resampling method, the derivation cohort and validation cohort (Harrell's C-index 0.695 and 0.667, respectively) showed good uniformity with the model. The constructed model accurately predicted cardiovascular events of MHD patients in the 3rd and 5th years after dialysis. And the further research is needed to determine whether use of the risk prediction tool improves clinical outcomes.

Development of human endogenous retrovirus type K- related treatments for human diseases.

Human endogenous retroviruses (HERVs) constitute approximately 8% of the human genome and have long been regarded as silent passengers within our genomes. However, the reactivation of HERVs has been increasingly linked to a range of human diseases, particularly the HERV-K (HML-2) family. Many studies are dedicated to elucidating the potential role of HERV-K in pathogenicity. While the underlying mechanisms require further investigation, targeting HERV-K transactivation emerges as a promising avenue for treating human diseases, including cancer, autoimmune disorders, neurodegenerative conditions, and infectious diseases. In this review, we summarize recent advancements in the development of HERV-K-targeted therapeutic strategies against various human diseases, including antiretroviral drugs, immunotherapy, and vaccines.

Influence of Rehabilitation Training-Based Procedural Follow-up on Pulmonary Function and Quality of Life in Patients Undergoing Coronary Angiography and Stenting.

Objective: This study aims to investigate the impact of procedural follow-up through rehabilitation training on enhancing postoperative pulmonary function and quality of life (QOL) in patients who have undergone coronary angiography and stenting. Methods: A total of 160 patients diagnosed with coronary heart disease (CHD) and having undergone percutaneous coronary intervention (PCI) between January 1, 2020, and December 31, 2021, were selected for the study. The random number method was employed to divide them into a control group and an experimental group. The control group (80 patients) received routine post-discharge follow-ups, while the experimental group (80 patients) underwent procedural follow-ups based on rehabilitation training. Pulmonary function and quality of life were assessed at discharge, 6 months post-discharge, and 12 months post-discharge using the Jaeger spirometer and the Assessment Scale of Quality of Life in Patients with CHD. Results: No statistically significant differences in pulmonary function and quality of life were observed between the two groups at the time of discharge (P > .05). However, 6 and 12 months post-discharge, the experimental group exhibited higher values for FEV1, FEV1%, FEV1/FVC, and VO2max compared to the control group. Additionally, total QOL scores, psychological function, and knowledge of CHD prevention and treatment were higher in the experimental group. However, there were no statistically significant differences in physical function and social adaptation ability. Conclusions: Procedural follow-ups based on rehabilitation training have the potential to improve postoperative cardiopulmonary function and quality of life in patients with coronary heart disease, thereby promoting recovery.

Human endogenous retrovirus type K encoded Np9 oncoprotein induces DNA damage response.

Human endogenous retrovirus sequences (HERVs) constitute up to 8% of the human genome, yet not all HERVs remain silent passengers within our genomes. Some HERVs, especially the HERV type K (HERV-K), have been found to be frequently transactivated in a variety of inflammatory diseases and human cancers. Np9, a 9-kDa HERV-K encoded protein, has been reported as an oncoprotein and found present in a variety of tumors and transformed cells. In the current study, we for the first time reported that ectopic expression of Np9 protein was able to induce DNA damage response from host cells especially through upregulation of γH2AX. Furthermore, we found that direct knockdown of Np9 by RNAi in Kaposi's Sarcoma-associated herpesvirus (KSHV) infected cells effectively reduced LANA expression, the viral major latent oncoprotein in vitro and in vivo, which may represent a novel strategy against virus-associated malignancies.

A nanopore-based cucumber genome assembly reveals structural variations at two QTLs controlling hypocotyl elongation.

The Xishuangbanna (XIS) cucumber (Cucumis sativus var. xishuangbannanesis) is a semiwild variety that has many distinct agronomic traits. Here, long reads generated by Nanopore sequencing technology helped assembling a high-quality genome (contig N50 = 8.7 Mb) of landrace XIS49. A total of 10,036 structural/sequence variations (SVs) were identified when comparing with Chinese Long (CL), and known SVs controlling spines, tubercles, and carpel number were confirmed in XIS49 genome. Two QTLs of hypocotyl elongation under low light, SH3.1 and SH6.1, were fine-mapped using introgression lines (donor parent, XIS49; recurrent parent, CL). SH3.1 encodes a red-light receptor Phytochrome B (PhyB, CsaV3_3G015190). A ∼4 kb region with large deletion and highly divergent regions (HDRs) were identified in the promoter of the PhyB gene in XIS49. Loss of function of this PhyB caused a super-long hypocotyl phenotype. SH6.1 encodes a CCCH-type zinc finger protein FRIGIDA-ESSENTIAL LIKE (FEL, CsaV3_6G050300). FEL negatively regulated hypocotyl elongation but it was transcriptionally suppressed by long terminal repeats retrotransposon insertion in CL cucumber. Mechanistically, FEL physically binds to the promoter of CONSTITUTIVE PHOTOMORPHOGENIC 1a (COP1a), regulating the expression of COP1a and the downstream hypocotyl elongation. These above results demonstrate the genetic mechanism of cucumber hypocotyl elongation under low light.

Biological characteristics of mechanosensitive channels MscS and MscL in Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae is an important respiratory pathogen that can cause porcine contagious pleuropneumonia (PCP), resulting in significant economic losses in swine industry. Microorganisms are subjected to drastic changes in environmental osmolarity. In order to alleviate the drastic rise or fall of osmolarity, cells activate mechanosensitive channels MscL and MscS through tension changes. MscL not only regulates osmotic pressure but also has been reported to secrete protein and uptake aminoglycoside antibiotic. However, MscL and MscS, as the most common mechanosensitive channels, have not been characterized in A. pleuropneumoniae. In this study, the osmotic shock assay showed that MscL increased sodium adaptation by regulating cell length. The results of MIC showed that deletion of mscL decreased the sensitivity of A. pleuropneumoniae to multiple antibiotics, while deletion of mscS rendered A. pleuropneumoniae hypersensitive to penicillin. Biofilm assay demonstrated that MscL contributed the biofilm formation but MscS did not. The results of animal assay showed that MscL and MscS did not affect virulence in vivo. In conclusion, MscL is essential for sodium hyperosmotic tolerance, biofilm formation, and resistance to chloramphenicol, erythromycin, penicillin, and oxacillin. On the other hand, MscS is only involved in oxacillin resistance.IMPORTANCEBacterial resistance to the external environment is a critical function that ensures the normal growth of bacteria. MscL and MscS play crucial roles in responding to changes in both external and internal environments. However, the function of MscL and MscS in Actinobacillus pleuropneumoniae has not yet been reported. Our study shows that MscL plays a significant role in osmotic adaptation, antibiotic resistance, and biofilm formation of A. pleuropneumoniae, while MscS only plays a role in antibiotic resistance. Our findings provide new insights into the functional characteristics of MscL and MscS in A. pleuropneumoniae. MscL and MscS play a role in antibiotic resistance and contribute to the development of antibiotics for A. pleuropneumoniae.

Developing new ceramide analogs against non-small cell lung cancer (NSCLC).

Non-small cell lung cancer (NSCLC) constitutes the predominant form of lung cancer and stands as the leading cause of cancer-related mortality in the United States. Conventional chemotherapy and radiotherapy yield suboptimal responses in a significant portion of lung cancer patients, resulting in a discouraging 5-year survival rate of approximately 15%. Despite advancements in targeted therapy and immunotherapy, many NSCLC patients exhibit either negligible or partial responses, emphasizing the pressing necessity for the discovery of innovative anti-cancer agents. Our previous study demonstrated that ABC294640, an inhibitor of one of the key enzymes in sphingolipid metabolism, sphingosine kinase 2 (SphK2), displayed anti-NSCLC activities in vitro and in vivo. In the current study, through the screening of a series of newly synthesized ceramide analogs, we have identified new compounds, particularly analogs 403 and 953, that exhibit potent anti-NSCLC activities. These compounds induce significant NSCLC apoptosis by elevating intracellular pre-apoptotic ceramide and dihydro(dh)-ceramide production. Lipidomics analyses further elucidate the alterations in ceramide and dh-ceramide species signature/proportion across different NSCLC cell-lines induced by these novel ceramide analogs. Treatments with ceramide analogs 403 and 953 remarkably inhibit NSCLC progression in vivo without observable toxicity. Collectively, these findings establish a foundation for the development of promising sphingolipid-based therapies aimed at enhancing the prognosis of NSCLC.

Role of lymphatic endothelium specific hyaluronan receptor 1 in virus infection and associated diseases.

Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) serves as a prominent marker for lymphatic endothelial cells (LECs) and is pivotal in the process of lymphangiogenesis, a critical factor in cancer development and metastasis. Overexpression of LYVE-1 has been observed in various cancers, where it is recognized as an adverse prognostic indicator. Targeting LYVE-1 has demonstrated inhibitory effects on tumor cell proliferation, migration, and the formation of lymph node metastases both in vitro and in vivo. While extensive research has focused on the role of LYVE-1 in cancer cells, its involvement in virus infection and associated diseases remains largely unexplored. This review consolidates recent findings regarding the expression of LYVE-1 and its functions in lymphangiogenesis during various viral infections and the development of related diseases, with a particular emphasis on Kaposi's sarcoma herpesvirus. Despite the limited available data, it is evident that further studies are essential to comprehensively understand the contribution of LYVE-1 to viral pathogenesis and oncogenesis.

Anti-diabetic and anti-inflammatory indole diterpenes from the marine-derived fungus Penicillium sp. ZYX-Z-143.

Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 µM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 µM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.

Association between cardiometabolic index and depression: National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Emerging evidence suggests a common pathophysiological basis for metabolic disorders and mental diseases. Despite the existence of reports suggesting a strong connection between dyslipidemia and depression, a comprehensive and reliable indicator to identify depression is still lacking. Cardiometabolic index (CMI) is an integrated index calculated from three vital metabolic indicators, including triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and waist height ratio (WHtR). OBJECTIVE: This study aims to explore the association between CMI and depression. METHODS: Cross-sectional data of participants with complete information of CMI, depression, and other covariates were obtained from the National Health and Nutrition Examination Survey (NHANES). Weighted student's t-test and Chi-square test were used to identify the differences between two groups. Weighted multivariate logistic regression model, restricted cubic spline (RCS) regression analysis, subgroup analysis and interaction tests were conducted to explore the association between CMI and depression. Receiver operating curve (ROC) analysis and area under the curve (AUC) were also utilized to evaluate the performance of CMI in identifying depression. RESULTS: A positive correlation between CMI and depression was observed in 3794 participants included in the study, which was further confirmed to be non-linear via RCS regression analysis, with two significant inflection points being identified, including 0.9522 and 1.58. In the crude or adjusted models, individuals with a CMI level ≥ 0.9522 exhibited remarkably increased risk for developing depression. CMI got an AUC of 0.748 in identifying depression. Subgroup analyses and interaction tests indicate that the association between CMI and depression remained consistent across different subgroups and was not modified by other covariates except drinking. Those who are current drinkers and with a high CMI are more susceptible to suffer depression. CONCLUSIONS: An elevated CMI is linked to increased risk for depression. Addressing dyslipidemia and improving lipid levels may potentially lower the risk for depression.

Comparative transcriptome profile reveals insight into the antibacterial immunity mechanism of the loach (Misgurnus anguillicaudatus) fed with soybean fermented broth during lipopolysaccharide (LPS) exposure.

Loach (Misgurnus anguillicaudatus) is a common freshwater commercial fish species in China. The meat of this fish is a good source of protein and other nutrients that are needed for human health. Aquaculture challenges such as diseases and pest susceptibility, excessive density, and nutritional deficiency result in low production of loach rather than increased demand. Due to a lack of knowledge about the immune system of loaches, we carried out this study to better understand its antibacterial molecular mechanism. Here, we performed RNA sequencing from liver tissue obtained from soya bean-fermented fed loach after subjecting it to the LPS challenge. The results revealed a total of 18,399 differentially expressed genes (DEGs) in the LPS-treated and control groups. There were 7482 DEGs that were upregulated and 10,917 DEGs were downregulated. The enrichment analysis of DEGs revealed that the majority of DEGs were found to be abundant in the pathways of DNA replication, spliceosome, nucleotide exception repair, cell cycle, and Herpes simplex virus 1 infection. Furthermore, qRT-PCR analysis of 21 selected DEGs demonstrated that the transcriptomic data is extremely reliable. Overall, this study provides insight into the molecular features and control mechanisms of genes that affect loach growth. The availability of this information will also contribute to the enhancement of the breeding and protection of loach resources.

Foxp2 deficiency impairs reproduction by modulating the hypothalamic-pituitary-gonadal axis in zebrafish†.

FOXP2 was initially characterized as a transcription factor linked to speech and language disorders. Single-cell RNA sequencing reveals that Foxp2 is enriched in the gonadotrope cluster of the pituitary gland and colocalized with the hormones LHB and FSHB in chickens and mice, implying that FOXP2 might be associated with reproduction in vertebrates. Herein, we investigated the roles of foxp2 in reproduction in a Foxp2-deficient zebrafish model. The results indicated that the loss of Foxp2 inhibits courtship behavior in adult male zebrafish. Notably, Foxp2 deficiency disrupts gonad development, leading to retardation of follicle development and a decrease in oocytes in females at the full-growth stage, among other phenotypes. The transcriptome analysis (RNA-seq) also revealed that differentially expressed genes clustered into the estrogen signaling and ovarian steroidogenesis-related signaling pathways. In addition, we found that Foxp2 deficiency could modulate the hypothalamic-pituitary-gonadal axis, especially the regulation of lhb and fshb expression, in zebrafish. In contrast, the injection of human chorionic gonadotropin, a specific LH agonist, partially rescues Foxp2-impaired reproduction in zebrafish, suggesting that Foxp2 plays an important role in the regulation of reproduction via the hypothalamic-pituitary-gonadal axis in zebrafish. Thus, our findings reveal a new role for Foxp2 in the regulation of reproduction in vertebrates.

Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions.

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

The potential interaction between chemosensitivity and the development of cardiovascular disease in obstructive sleep apnea.

OBJECTIVES: Chemosensitivity is an essential part of the pathophysiological mechanisms of obstructive sleep apnea (OSA). Not only does OSA have a certain relationship with the comorbidity of cardiovascular disease (CVD) but also chemosensitivity plays a crucial role in the development of CVD. This study aims to investigate the potential interaction between chemosensitivity and the development of CVD in OSA. METHODS: A total of 169 participants with suspected OSA were included. Data were gathered on the parameters of polysomnography and baseline clinical features. Peripheral chemosensitivity was evaluated by employing the rebreathing test. The lifetime CVD risk was computed using the China-PAR (Prediction for atherosclerotic CVD Risk in China) risk equation. RESULTS: After controlling for covariates, participants with chemosensitivity levels in the second and fifth quantiles tended to hold an increased proportion of high lifetime CVD risk (OR 10.90, 95%CI [2.81-42.28]; OR 6.78, 95%CI [1.70-27.05], respectively). The diagnosis of OSA would significantly increase the 10-year and lifetime CVD risks in participants with low chemosensitivity, while no such differences were found in participants with high chemosensitivity. CONCLUSION: Higher lifetime CVD risk was associated with participants who had greater peripheral chemosensitivity. In terms of the CVD outcomes, adult patients with a relatively low level of chemosensitivity may be primarily related to their diagnosis of OSA, whereas adult patients with a relatively high level of chemosensitivity may be more strongly associated with their elevated levels of chemosensitivity rather than OSA.