Identification of bioactive ingredients and potential mechanisms of flowers of Hosta Plantaginea in treating pneumonia based on network pharmacology and experimental validation.

Flowers of Hosta plantaginea (H. plantaginea), a widely utilized medicinal herb in Mongolian medicine, holds a significant historical background in terms of its medicinal applications. This herb is renowned for its ability to clear heat and detoxify the body, alleviate cough, and provide relief to the throat. However, the active ingredients and the potential mechanism of action remain ambiguity. The objective of this study was to conduct a comprehensive analysis of the efficacy of H. plantaginea in treating pneumonia, identify its active ingredients and unveil the pharmacological mechanism in the treatment of pneumonia. In vivo experiments demonstrate the plant's anti-pneumonia properties, while mass spectrometry analysis identifies 62 chemicals, with 14 absorbed into the bloodstream. Network pharmacology and Venn analysis reveal 195 targets of 52 active ingredients, with 49 gene targets common to H. plantaginea and pneumonia. Protein-protein interaction (PPI) network construction and enrichment analysis highlight the key targets and pathways such as AKT, EGFR, IL-17. Western blotting confirms downregulation of these pathways, indicating the anti-inflammatory effects of H. plantaginea in treating acute lung injury. Our findings showed that the treatment of ALI with the H. plantaginea exerts its anti-inflammatory effects through multiple components, targets, and pathways. This study established a solid experimental foundation for investigating the various components, targets, and pathways involved in the treatment of pneumonia using H. plantaginea. It offers valuable insights from multiple perspectives and can serve as a reference for the clinical application of this plant in pneumonia treatment.

Mito-tempo alleviates ox-LDL-provoked foam cell formation by regulating Nrf2/NLRP3 signaling.

Our previous studies have demonstrated that Mito-Tempol (also known as 4-hydroxy-Tempo), a mitochondrial reactive oxygen species (ROS) scavenger, alleviates oxidized low-density lipoprotein (ox-LDL)-triggered foam cell formation. Given the effect of oxidative stress on activating the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome, which promotes foam cell formation, we aimed to explore whether Mito-Tempo inhibits ox-LDL-triggered foam cell formation by regulating NLRP3 inflammasome. The results revealed that Mito-Tempo re-activated Nrf2 and alleviated macrophage foam cell formation induced by ox-LDL, whereas the effects were reversed by ML385 (a specific Nrf2 inhibitor). Mito-Tempo restored the expression and nuclear translocation of Nrf2 by decreasing ox-LDL-induced ubiquitination. Furthermore, Mito-Tempo suppressed ox-LDL-triggered NLRP3 inflammasome activation and subsequent pyroptosis, whereas the changes were blocked by ML385. Mito-Tempo decreased lipoprotein uptake by inhibiting CD36 expression and suppressed foam cell formation by regulating the NLRP3 inflammasome. Taken together, Mito-Tempo exhibits potent anti-atherosclerotic effects by regulating Nrf2/NLRP3 signaling.

An Immune-Regulating Polysaccharide Hybrid Hydrogel with Mild Photothermal Effect and Anti-Inflammatory for Accelerating Infected Wound Healing.

Bacterial infections and excessive inflammation present substantial challenges for clinical wound healing. Hydrogels with mild photothermal (PTT) effects have emerged as promising agents owing to their dual actions: positive effects on cells and negative effects on bacteria. Here, an injectable self-healing hydrogel of oxidized konjac glucomannan/arginine-modified chitosan (OKGM/CS-Arg, OC) integrated with protocatechualdehyde-@Fe (PF) nanoparticles capable of effectively absorbing near-infrared radiation is synthesized successfully. The OC/PF hydrogels exhibit excellent mechanical properties, biocompatibility, and antioxidant activity. Moreover, in synergy with PTT, OC/PF demonstrates potent antibacterial effects while concurrently stimulating cell migration and new blood vessel formation. In methicillin-resistant Staphylococcus aureus-infected full-thickness mouse wounds, the OC/PF hydrogel displays remarkable antibacterial and anti-inflammatory activities, and accelerates wound healing by regulating the wound immune microenvironment and promoting M2 macrophage polarization. Consequently, the OC/PF hydrogel represents a novel therapeutic approach for treating multidrug-resistant bacterial infections and offers a technologically advanced solution for managing infectious wounds in clinical settings.

Prior COVID-19 vaccination and reduced risk of cerebrovascular diseases among COVID-19 survivors.

The effects of COVID-19 vaccination on short-term and long-term cerebrovascular risks among COVID-19 survivors remained unknown. We conducted a national multi-center retrospective cohort study with 151 597 vaccinated and 151 597 unvaccinated COVID-19 patients using the TriNetX database, from January 1, 2020 to December 31, 2023. Patients baseline characteristics were balanced with propensity score matching (PSM). The outcomes were incident cerebrovascular diseases occurred between 1st and 30th days (short-term) after COVID-19 diagnosis. Nine subgroup analyses were conducted to explore potential effect modifications. We performed six sensitivity analyses, including evaluation of outcomes between 1st to 180th days, accounting for competing risk, and incorporating different variant timeline to test the robustness of our results. Kaplan-Meier curves and Log-Rank tests were performed to evaluate survival difference. Cox proportional hazards regressions were adopted to estimate the PSM-adjusted hazard ratios (HR). The overall short-term cerebrovascular risks were lower in the vaccinated group compared to the unvaccinated group (HR: 0.66, 95% CI: 0.56-0.77), specifically cerebral infarction (HR: 0.62, 95% CI: 0.48-0.79), occlusion and stenosis of precerebral arteries (HR: 0.74, 95% CI: 0.53-0.98), other cerebrovascular diseases (HR: 0.57, 95% CI: 0.42-0.77), and sequelae of cerebrovascular disease (HR: 0.39, 95% CI:0.23-0.68). Similarly, the overall cerebrovascular risks were lower in those vaccinated among most subgroups. The long-term outcomes, though slightly attenuated, were consistent (HR: 0.80, 95% CI: 0.73-0.87). Full 2-dose vaccination was associated with a further reduced risk of cerebrovascular diseases (HR: 0.63, 95% CI: 0.50-0.80) compared to unvaccinated patients. Unvaccinated COVID-19 survivors have significantly higher cerebrovascular risks than their vaccinated counterparts. Thus, clinicians are recommended to monitor this population closely for stroke events during postinfection follow-up.

ROS-responsive nano-medicine for navigating autophagy to enhance targeted therapy of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder characterized by immune dysregulation and intestinal inflammation. Rapamycin (Ra), an mTORC1 pathway inhibitor, has shown promise for autophagy induction in IBD therapy but is associated with off-target effects and toxicity. To address these issues, we developed an oral liposome responsive to reactive oxygen species (ROS) using lipids and amphiphilic materials. We combined ketone thiol (TK) for ROS responsive and hyaluronic acid (HA) with high affinity for CD44 receptors to prepare rapamycin-loaded nanoparticle (Ra@TH). Owing to its ROS responsive characteristic, Ra@TH can achieve inflammatory colonic targeting. Additionally, Ra@TH can induce autophagy by inhibiting the mTORC1 pathway, leading to the clearance of damaged organelles, pathogenic microorganisms and oxidative stress products. Simultaneously, it also collaboratively inhibits the NF-κB pathway suppressed by the removal of ROS resulting from TK cleavage, thereby mediating the expression of inflammatory factors. Furthermore, Ra@TH enhances the expression of typical tight junction proteins, synergistically restoring intestinal barrier function. Our research not only expands the understanding of autophagy in IBD treatment but also introduces a promising therapeutic approach for IBD patients.

Abnormal expression of Krüppel-like transcription factors and their potential values in lung cancer.

Lung cancer still is one of the most common malignancy tumors in the world. However, the mechanisms of its occurrence and development have not been fully elucidated. Zinc finger protein family (ZNFs) is the largest transcription factor family in human genome. Recently, the more and more basic and clinical evidences have confirmed that ZNFs/Krüppel-like factors (KLFs) refer to a group of conserved zinc finger-containing transcription factors that are involved in lung cancer progression, with the functions of promotion, inhibition, dual roles and unknown classifications. Based on the recent literature, some of the oncogenic KLFs are promising molecular biomarkers for diagnosis, prognosis or therapeutic targets of lung cancer. Interestingly, a novel computational approach has been proposed by using machine learning on features calculated from primary sequences, the XGBoost-based model with accuracy of 96.4 % is efficient in identifying KLF proteins. This paper reviews the recent some progresses of the oncogenic KLFs with their potential values for diagnosis, prognosis and molecular target in lung cancer.

CircGPC3 promotes hepatocellular carcinoma progression and metastasis by sponging miR-578 and regulating RAB7A/PSME3 expression.

CircRNAs are a class of highly stable noncoding RNAs that play an important role in the progression of many diseases, especially cancer. In this study, high-throughput sequencing was used to screen for abnormally expressed circRNAs, and we found that circGPC3 was overexpressed in HCC tissues. However, the underlying mechanism of circGPC3 in the development and metastasis of hepatocellular carcinoma (HCC) remains unknown. In our study, we found that circGPC3 was significantly upregulated in HCC tissues and cells and that its overexpression was positively correlated with overall survival, TNM stage and lymph node metastasis. In vivo and in vitro experiments showed that circGPC3 knockdown repressed HCC cell migration, invasion and proliferation and promoted apoptosis. Mechanistically, circGPC3 promoted HCC proliferation and metastasis through the miR-578/RAB7A/PSME3 axis. Our results demonstrate that circGPC3 contributes to the progression of HCC and provides an intervention target for HCC.

Increased Risk of Inflammatory Bowel Disease Among Patients With Nontyphoidal Salmonella Infections: A Population-Based Cohort Study.

BACKGROUND: Despite the known association between microorganisms and development of inflammatory bowel disease (IBD), the role of nontyphoidal Salmonella (NTS) in IBD is not adequately addressed. We aimed at elucidating the relationship between NTS infection and the risk of IBD. METHODS: Based on the National Health Insurance Research Database in Taiwan, this retrospective cohort study enrolled patients with NTS infection (exposure group; n = 4651) and those without NTS infection (comparator group; n = 4651) who were propensity score matched (1:1) by demographic data, medications, comorbidities, and index date. All patients were followed until IBD onset, individual mortality, or December 31, 2018. Cox proportional hazards regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs). Sensitivity analyses were used for cross-validation. RESULTS: The NTS group demonstrated an increased risk of IBD compared with the non-NTS groups (adjusted hazard ratio [aHR], 2.12; 95% CI, 1.62-2.78) with a higher risk of developing ulcerative colitis in the former (aHR, 2.27; 95% CI, 1.69-3.04). Nevertheless, the small sample size may contribute to lack of significant difference in Crohn's disease. Consistent findings were noted after excluding IBD diagnosed within 6 months of NTS infection (aHR, 2.28; 95% CI, 1.71-3.03), excluding those with enteritis/colitis before index date (aHR, 1.85; 95% CI, 1.28-2.68), excluding those using antibiotics for 1 month in the year before IBD onset (aHR, 1.81; 95% CI, 1.34-2.45), inverse probability of treatment weighting (aHR, 1.64; 95% CI, 1.31-2.04), and inclusion of individuals regardless of age (n = 10 431; aHR, 1.83; 95% CI, 1.53-2.19). CONCLUSIONS: Patients with NTS were associated with an increased risk of developing IBD, especially ulcerative colitis.

The Potential Mediating Effect of Symptom Burden on Demoralization Through Locus of Control and Coping Strategies in Chinese Patients With Cancer.

BACKGROUND: Demoralization is a psychological syndrome that is highly prevalent in patients with cancer and detrimental to individuals' physical and mental health. To explore effective intervention, we first determined the relationships between locus of control, coping strategies, symptom burden, and demoralization. OBJECTIVE: The aim of this study was to determine the relationship between symptom burden, locus of control, coping strategies, and demoralization in patients with cancer. METHODS: In this descriptive-correlational study, 273 valid patients were selected with convenience sampling method from a hospital in China. Data were collected using the Chinese version of the M.D. Anderson Symptom Inventory, the Chinese version of the Multidimensional Health Locus of Control Scale, the Chinese version of the Medical Coping Modes Questionnaire, and the Mandarin version of the Demoralization Scale. Data were analyzed using descriptive and inferential statistics using SPSS and AMOS. RESULTS: A total of 115 patients (42.12%) experienced clinical demoralization (Mandarin version of the Demoralization Scale > 30). Symptom burden (ß = 0.295, P < .001), confrontation (ß = -0.117, P = .028), and resignation (ß = 0.456, P < .001) had direct effects on demoralization. Symptom burden also had an indirect effect on demoralization through the mediating role of resignation (ß = 0.026, P = .002). Meanwhile, locus of control can affect demoralization entirely through the indirect mediating role of coping strategies (chance locus of control via resignation [ß = 0.138, P < .01], powerful locus of control via confrontation [ß = -0.017, P < .05]). CONCLUSIONS: Symptom burden affects demoralization not only directly but also indirectly. Coping strategies play an important mediating role between symptom burden, locus of control, and demoralization in patients with cancer. IMPLICATIONS FOR PRACTICE: It is urgent to screen demoralization and identify patients with high symptom burden, maladaptive locus of control, or coping strategies. For the patients targeted, a more comprehensive and systematic approach to symptom management and more appropriate guidance related to adaptive coping strategies are needed.

Maternal human papillomavirus infection and the risk of congenital malformations: A nationwide population-based cohort study.

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.

Time-dependent risk of atopic dermatitis following nontyphoidal Salmonella infection.

BACKGROUND: The pathogenesis of atopic dermatitis (AD) remains unclear. Nontyphoidal Salmonella (NTS) infection might trigger immune-mediated reactions. We aimed to examine NTS and the risk of subsequent AD. METHODS: From 2002 to 2015, eligible patients (aged 0-100 years) with NTS were identified. NTS and non-NTS groups were matched at a 1:10 ratio on age and sex. We utilized conditional multivariable Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for AD development. Subgroup analyses were conducted based on age, sex, and severity of NTS infection. We utilized landmark analysis to explore the time-dependent hazard of AD following NTS. RESULTS: In the NTS group (N = 6624), 403 developed AD. After full adjustment of demographics and comorbidities, the NTS group had a higher risk of AD than the reference group (aHR = 1.217, 95% CI = 1.096-1.352). Age-stratified analysis revealed that NTS group exhibited an elevated risk compared to the reference group, particularly among those aged 13-30 years (aHR = 1.25, 95% CI = 1.017-1.559), individuals aged 31-50 years (aHR = 1.388, 95% CI = 1.112-1.733), those aged 51-70 years (aHR = 1.301, 95% CI = 1.008-1.679), and individuals aged 71 years and over (aHR = 1.791, 95% CI = 1.260-2.545). Severe NTS was associated with a higher risk of AD than the reference group (aHR = 2.411, 95% CI = 1.577-3.685). Landmark analysis showed generally consistent findings. CONCLUSIONS: Minimizing exposure to NTS infection may represent a prospective strategy for averting the onset and progression of atopic dermatitis.

Communication molecules (ncRNAs) mediate tumor-associated macrophage polarization and tumor progression.

Non-coding RNAs play important roles in tumor cells and macrophages and participate in their communication as messengers. Non-coding RNAs have an impact in tumor cell proliferation, migration, and apoptosis, and they also regulate the differentiation and regulation of immune cells. In macrophages, they stimulate the polarization of macrophages into M1 or M2 by regulating proteins related to signaling pathways; in tumor cells, non-coding RNAs can enter macrophages through exosomes and affect the latter polarization. The polarization of macrophages further regulates the biological functions of cancer cells. The direction of macrophage polarization determines tumor progression, angiogenesis and drug resistance. This often creates a feedback loop. Non-coding RNAs act as bridges between tumor cells and macrophages to regulate the balance of the tumor microenvironment. We reviewed the signaling pathways related to macrophage polarization and the regulatory mechanisms of non-coding RNA in tumor-associated macrophages M1 and M2, and discussed the potential applications and prospects of exosome engineering.

[3-Deazaadenosine (3-DAA) accelerates Japanese encephalitis virus replication and down-regulates levels of inflammatory factors in mouse and hamster cells].

Objective To investigate the effect of 3-deazaadenosine (3-DAA), an N6-methyladenosine (m6A) methylation modification inhibitor, on the replication of the Japanese encephalitis virus (JEV). Methods Neuro2a mouse neuroblastoma cells, N9 mouse microglial cells, and BHK baby hamster kidney cells were exposed to JEV and then treated with 3-DAA. JEV was also injected into the footpad of adult C57BL/6 mice, which were then administered 3-DAA intraperitoneally. Real-time quantitative PCR was utilized to measure mRNA expression levels of JEV, interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), interferon (IFN)-α, IFN-ß, IFN-γ, and C-X-C motif chemokine ligand 10 (CXCL10) in the cells and mouse brain tissues. Western blot analysis was used to detect JEV protein expression in the cells and mouse brain tissues. Furthermore, the survival of the mice was monitored and pathological changes in mouse brains were observed via hematoxylin and eosin (HE) staining. Results 3-DAA had a dose-dependent effect on the replication of RNA and protein expression of JEV in both BHK, N9, Neuro 2α cells and mouse brain tissues, which resulted in rapid progression of JEV infection in mice and a decrease in their survival rate. Furthermore, 3-DAA suppressed the expression of inflammatory factors such as IL-6, TNF-α, CXCL10, IL-1ß and iNOS, thus weakening the immune response. Conclusion 3-DAA promotes JEV infection and hastens death of infected cells and mice, indicating that m6A modification may negatively regulate JEV replication.

Targeting the nuclear long noncoding transcript LSP1P5 abrogates extracellular matrix deposition by trans-upregulating CEBPA in keloids.

Keloids are characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix (ECM) and are a major global health care burden among cutaneous diseases. However, the function of long noncoding RNA (lncRNA)-mediated ECM remodeling during the pathogenesis of keloids is still unclear. Herein, we identified a long noncoding transcript, namely, lymphocyte-specific protein 1 pseudogene 5 (LSP1P5), that modulates ECM component deposition in keloids. First, high-throughput transcriptome analysis showed that LSP1P5 was selectively upregulated in keloids and correlated with more severe disease in a clinical keloid cohort. Therapeutically, the attenuation of LSP1P5 significantly decreased the expression of ECM markers (COL1, COL3, and FN1) both in vitro and in vivo. Intriguingly, an antifibrotic gene, CCAAT enhancer binding protein alpha (CEBPA), is a functional downstream candidate of LSP1P5. Mechanistically, LSP1P5 represses CEBPA expression by hijacking Suppressor of Zeste 12 to the promoter of CEBPA, thereby enhancing the polycomb repressive complex 2-mediated H3K27me3 and changing the chromosomal opening status of CEBPA. Taken together, these findings indicate that targeting LSP1P5 abrogates fibrosis in keloids through epigenetic regulation of CEBPA, revealing a novel antifibrotic therapeutic strategy that bridges our current understanding of lncRNA regulation, histone modification and ECM remodeling in keloids.

Association of diverticulitis and potential risk of ischemic stroke: population-based matched cohort study in Taiwan.

BACKGROUND: Previous studies have suggested relationship between diverticular disease and cardiovascular disease. Since cardiovascular disease and cerebrovascular accident share a lot of pathogenesis, diverticulitis could also be a risk factor for stroke. This study tried to establish epidemiological evidence of the relationship between colon diverticulitis and ischemic stroke. METHODS: In this retrospective cohort study, patients with newly diagnosed colon diverticulitis (N = 6238) and patients without colon diverticulitis (control group; N = 24 952) were recruited between January 1, 2000, and December 31, 2017. Both groups were matched by propensity score at a 1:4 ratio by age, sex, comorbidities and medications. Cox proportional hazard regression was applied to estimate the hazard ratio (HR) and 95% confidence interval (CI) of ischemic stroke. We also conducted 4 different regression models and 2 sensitivity analyses to test the robustness of our findings. RESULTS: The diverticulitis group had a higher risk of IS than the control group (adjusted HR, 1.25; 95% CI, 1.12-1.39; P < 0.001). Serial sensitivity analyses yielded consistent positive link between diverticulitis and IS. Further subgroup analysis showed that in the study group, the risk of IS was 2.54-fold higher than the matched controls in 30-39 years. CONCLUSIONS: Our study found that colon diverticulitis was associated with a higher risk of developing subsequent ischemic stroke, especially for patients aged 30-39 years, among Asian population. This result provides us a chance to undertake preventive measures for ischemic stroke in high-risk patients.

Recent Progress in Modular Electrochemical Synthesis of Hydrogen and High-Value-added Chemicals based on Solid Redox Mediator.

Electrochemical synthesis of H2 and high-value-added chemicals is an efficient and cost-effective approach that can be powered using renewable electricity. Compared to a conventional electrochemical production system, the modular electrochemical production system (MEPS) based on a solid redox mediator (SRM) can separate the anodic and cathodic reactions in time and space. The MEPS can avoid the use of membranes and formation of useless products, as well as eliminate the mutual dependence of production rates at anode and cathode. The SRM can temporarily store or release electrons and ions to pair with cathodic and anodic reactions, respectively, in MEPS. Designing of SRMs with large charge capacity and good cyclability is of great significance for constructing a high-performance MEPS. This work summarizes the design principles, recent advances in MEPS based on SRM, and application in redox flow cells. Moreover, structure design strategies as well as in situ characterization techniques and theoretical calculations for SRM is also proposed. It is expected to promote the vigorous development of MEPS based on SRM. Finally, the challenges and perspectives of MEPS based on SRM are discussed.

Integrated multi-omics analysis reveals gut microbiota dysbiosis and systemic disturbance in major depressive disorder.

Major depressive disorder (MDD) involves systemic changes in peripheral blood and gut microbiota, but the current understanding is incomplete. Herein, we conducted a multi-omics analysis of fecal and blood samples obtained from an observational cohort including MDD patients (n = 99) and healthy control (HC, n = 50). 16S rRNA sequencing of gut microbiota showed structural alterations in MDD, as characterized by increased Enterococcus. Metagenomics sequencing of gut microbiota showed substantial functional alterations including upregulation in the superpathway of the glyoxylate cycle and fatty acid degradation and downregulation in various metabolic pathways in MDD. Plasma metabolomics revealed decreased amino acids and bile acids, together with increased sphingolipids and cholesterol esters in MDD. Notably, metabolites involved in arginine and proline metabolism were decreased while sphingolipid metabolic pathway were increased. Mass cytometry analysis of blood immune cell subtypes showed rises in proinflammatory immune subsets and declines in anti-inflammatory immune subsets in MDD. Furthermore, our findings revealed disease severity-related factors of MDD. Interestingly, we classified MDD into two immune subtypes that were highly correlated with disease relapse. Moreover, we established discriminative signatures that differentiate MDD from HC. These findings contribute to a comprehensive understanding of the MDD pathogenesis and provide valuable resources for the discovery of biomarkers.

Identification of environment-insensitive genes for oil content by combination of transcriptome and genome-wide association analysis in rapeseed.

BACKGROUND: The primary objective of rapeseed breeding is to enhance oil content, which is predominantly influenced by environmental factors. However, the molecular mechanisms underlying the impact of these environmental factors on oil accumulation remain inadequately elucidated. In this study, we used transcriptome data from two higher (HOC) and two lower oil content (LOC) inbred lines at 35 days after pollination (DAP) to investigate genes exhibiting stable expression across three different environments. Meanwhile, a genome-wide association study (GWAS) was utilized to detect candidate genes exhibiting significant associations with seed oil content across three distinct environments. RESULTS: The study found a total of 405 stable differentially expressed genes (DEGs), including 25 involved in lipid/fatty acid metabolism and 14 classified as transcription factors. Among these genes, BnBZIP10-A09, BnMYB61-A06, BnAPA1-A08, BnPAS2-A10, BnLCAT3-C05 and BnKASIII-C09 were also found to exhibit significant associations with oil content across multiple different environments based on GWAS of 50 re-sequenced semi-winter rapeseed inbred lines and previously reported intervals. Otherwise, we revealed the presence of additive effects among BnBZIP10-A09, BnKASIII-C09, BnPAS2-A10 and BnAPA1-A08, resulting in a significant increase in seed oil content. Meanwhile, the majority of these stable DEGs are interconnected either directly or indirectly through co-expression network analysis, thereby giving rise to an elaborate molecular network implicated in the potential regulation of seed oil accumulation and stability. CONCLUSIONS: The combination of transcription and GWAS revealed that natural variation in six environment-insensitive gene regions exhibited significant correlations with seed oil content phenotypes. These results provide important molecular marker information for us to further improve oil content accumulation and stability in rapeseed.

Network pharmacology analysis and animal experiment validation of neuroinflammation inhibition by total ginsenoside in treating CSM.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a degenerative pathology that affects both upper and lower extremity mobility and sensory function, causing significant pressure on patients and society. Prior research has suggested that ginsenosides may have neuroprotective properties in central nervous system diseases. However, the efficacy and mechanism of ginsenosides for CSM have yet to be investigated. PURPOSE: This study aims to analyze the composition of ginsenosides using UPLC-MS, identify the underlying mechanism of ginsenosides in treating CSM using network pharmacology, and subsequently confirm the efficacy and mechanism of ginsenosides in rats with chronic spinal cord compression. METHODS: UPLC-Q-TOF-MS was utilized to obtain mass spectrum data of ginsenoside samples. The chemical constituents of the samples were analyzed by consulting literature reports and relevant databases. Ginsenoside and CSM targets were obtained from the TCMSP, OMIM, and GeneCards databases. GO and KEGG analyses were conducted, and a visualization network of ginsenosides-compounds-key targets-pathways-CSM was constructed, along with molecular docking of key bioactive compounds and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenosides on CSM. Chronic spinal cord compression rats were intraperitoneally injected with ginsenosides (50 mg/kg and 150 mg/kg) and methylprednisolone for 28 days, and motor function was assessed to investigate the therapeutic efficacy of ginsenosides for CSM. The expression of proteins associated with TNF, IL-17, TLR4/MyD88/NF-κB, and NLRP3 signaling pathways was assessed by immunofluorescence staining and western blotting. RESULTS: Using UPLC-Q-TOF-MS, 37 compounds were identified from ginsenoside samples. Furthermore, ginsenosides-compounds-key targets-pathways-CSM visualization network indicated that ginsenosides may modulate the PI3K-Akt signaling pathway, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway and Apoptosis by targeting AKT1, TNF, MAPK1, CASP3, IL6, and IL1B, exerting a therapeutic effect on CSM. By attenuating neuroinflammation through the TNF, IL-17, TLR4/MyD88/NF-κB, and MAPK signaling pathways, ginsenosides restored the motor function of rats with CSM, and ginsenosides 150 mg/kg showed better effect. This was achieved by reducing the phosphorylation of NF-κB and the activation of the NLRP3 inflammasome. CONCLUSIONS: The results of network pharmacology indicate that ginsenosides can inhibit neuroinflammation resulting from spinal cord compression through multiple pathways and targets. This finding was validated through in vivo tests, which demonstrated that ginsenosides can reduce neuroinflammation by inhibiting NLRP3 inflammasomes via multiple signaling pathways, additionally, it should be noted that 150 mg/kg was a relatively superior dose. This study is the first to verify the intrinsic molecular mechanism of ginsenosides in treating CSM by combining pharmacokinetics, network pharmacology, and animal experiments. The findings can provide evidence for subsequent clinical research and drug development.

The effect of magnetic coupling along the magnetic axis on slow magnetic relaxation in DyIII complexes with D5h configuration based on an aggregation-induced-emission-active ligand.

The adjustment of crystal symmetry and intramolecular magnetic coupling is of great importance for the construction of high-performance single-molecule magnets. By using an aggregation-induced-emission-active pyridine-carbohydrazone-based Schiff base ligand and phosphine oxides, four dinuclear and one one-dimensional DyIII-based complexes, [Dy2(TPE-pc)2(Bu3PO)2Cl2]·2CH3CN·2H2O (1), [Dy2(TPE-pc)2(Cy3PO)2Cl2] (2), [Dy2(TPE-pc)2(MePA)2Cl2]·2CH3OH (3), [Dy2(TPE-pc)2(Ph3PO)2Cl2]2 (4) and [Dy2(TPE-pc)2(DPPO)Cl2]n (5) (H2TPE-pc = (E)-N'-(2-hydroxy-5-(1,2,2-triphenylvinyl)benzylidene)picolinohydrazide, MePA = N-phenyl-N',N''-bis(morpholinyl) phosphoric triamide, DPPO = piperazine-1,4-diylbis(diphenyl phosphine oxide)), were isolated. All complexes are made up of an enol oxygen-bridged Dy2 unit, where DyIII ions possess a pentagonal bipyramidal geometry with pseudo D5h symmetry. Magnetic measurements reveal that intramolecular DyIII-DyIII couplings are ferromagnetic and all complexes display a significant slow magnetic relaxation phenomenon below 30 K under a zero dc field. Ab initio calculations indicate that the anisotropic magnetic axes of all DyIII ions are approximately perpendicular to the higher-order symmetric axes in all complexes, and that DyIII-DyIII magnetic couplings along the magnetic axes effectively suppress the ground state quantum tunneling effect of magnetization and promote the occurrence of slow magnetic relaxation. Raman relaxation prevails in all complexes. In addition, the H2TPE-pc ligand shows an aggregation-induced emission (AIE) effect; however, all complexes exhibit an aggregation-caused quenching (ACQ) phenomenon.