COVID-19 vaccinations for patients with epilepsy in Guizhou Province, China: A cross-sectional study.

Several COVID-19 vaccines have been approved for emergency use according to China's immunization programs. These vaccines has created hope for patients with epilepsy, because the vaccines can help to reduce their risk of becoming infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to investigate the COVID-19 vaccine safety in patients with epilepsy. Here, we assessed the time of symptom control and the features of adverse events of seizure patients following their COVID-19 vaccinations. The results showed that adverse events of COVID-19 vaccinations for epilepsy patients included local pain at the injection site, dizziness and headache, epileptic attack, somnolence, limb weakness, limb pain, allergy, and fever. In addition, the average recovery time of the adverse events was approximately 42 h. More importantly, our study showed that it was relatively safe to vaccinate epilepsy patients who did not experience seizures for approximately 12 months prior to the immunization date.

Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans.

Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.

Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains in mice.

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-RBD antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

Mitochondrial bioenergetics: coupling of transport to tubular mitochondrial metabolism.

PURPOSE OF REVIEW: Renal tubules have robust active transport and mitochondrial metabolism, which are functionally coupled to maintain energy homeostasis. Here, I review the current literature and our recent efforts to examine mitochondrial adaptation to different transport activities in renal tubules. RECENT FINDINGS: The advance of extracellular flux analysis (EFA) allows real-time assessments of mitochondrial respiration, glycolysis, and oxidation of energy substrates. We applied EFA assays to freshly isolated mouse proximal tubules, thick ascending limbs (TALs), and distal convoluted tubules (DCTs) and successfully differentiated their unique metabolic features. We found that TALs and DCTs adjusted their mitochondrial bioenergetics and biogenesis in response to acute and chronic alterations of transport activity. Based on the literature and our recent findings, I discuss working models and mechanisms underlying acute and chronic tubular adaptations to transport activity. The potential roles of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), AMP-activated protein kinase (AMPK), and uncoupling protein 2 (UCP2) are discussed. SUMMARY: Mitochondria in renal tubules are highly plastic to accommodate different transport activities. Understanding the mechanisms may improve the treatment of renal tubulopathies.

Sequential radical and cationic reactivity at separated sites within one molecule in solution.

Distonic radical cations (DRCs) with spatially separated charge and radical sites are expected to show both radical and cationic reactivity at different sites within one molecule. However, such "dual" reactivity has rarely been observed in the condensed phase. Herein we report the isolation of crystalline 1λ2,3λ2-1-phosphonia-3-phosphinyl-cyclohex-4-enes 2a,b˙+, which can be considered delocalized DRCs and were completely characterized by crystallographic, spectroscopic, and computational methods. These DRCs contain a radical and cationic site with seven and six valence electrons, respectively, which are both stabilized via conjugation, yet remain spatially separated. They exhibit reactivity that differs from that of conventional radical cations (CRCs); specifically they show sequential radical and cationic reactivity at separated sites within one molecule in solution.

Five undescribed cyclopeptides from Cordyceps militaris.

Ustiloxins I-M (1-5), five undescribed cyclopeptides bearing a 15-membered macrocyclic skeleton, were isolated from Cordyceps militaris. The structures of 1 and 5 were identified by spectroscopic and crystallographic methods, whereas the structures of 2-4 were assigned by spectroscopic and computational approaches. Biological evaluation of all the compounds toward human triple-negative breast cancer cells revealed that compounds 4 and 5 are toxic with IC50 values of 64.29 µM and 28.89 µM, respectively.

Graph neural network based on brain inspired forward-forward mechanism for motor imagery classification in brain-computer interfaces.

Introduction: Within the development of brain-computer interface (BCI) systems, it is crucial to consider the impact of brain network dynamics and neural signal transmission mechanisms on electroencephalogram-based motor imagery (MI-EEG) tasks. However, conventional deep learning (DL) methods cannot reflect the topological relationship among electrodes, thereby hindering the effective decoding of brain activity. Methods: Inspired by the concept of brain neuronal forward-forward (F-F) mechanism, a novel DL framework based on Graph Neural Network combined forward-forward mechanism (F-FGCN) is presented. F-FGCN framework aims to enhance EEG signal decoding performance by applying functional topological relationships and signal propagation mechanism. The fusion process involves converting the multi-channel EEG into a sequence of signals and constructing a network grounded on the Pearson correlation coeffcient, effectively representing the associations between channels. Our model initially pre-trains the Graph Convolutional Network (GCN), and fine-tunes the output layer to obtain the feature vector. Moreover, the F-F model is used for advanced feature extraction and classification. Results and discussion: Achievement of F-FGCN is assessed on the PhysioNet dataset for a four-class categorization, compared with various classical and state-of-the-art models. The learned features of the F-FGCN substantially amplify the performance of downstream classifiers, achieving the highest accuracy of 96.11% and 82.37% at the subject and group levels, respectively. Experimental results affirm the potency of FFGCN in enhancing EEG decoding performance, thus paving the way for BCI applications.

Revealing the variances in color formation and bioactivities of seven catechin monomers throughout the enzymatic reaction by colorimetric and mass spectrometry.

The capacity differences of seven catechin monomers to produce colors after treating with catechin-free extract were investigated. After 240-min reaction, only (-)-epicatechin (EC) and (+)-catechin (C) presented obvious luminous red color with L* values of 63.32-71.73, a* values of 37.13-46.44, and b* values of 65.64-69.99. Meanwhile, the decrease rate of EC and C was 43.52 %-50.35 %, which were significantly lower than those of other catechin monomers (85.91 %-100 %). The oxidized products of catechin monomers were analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry coupled with diode array detector, wherein dehydro-dimers and -trimers (oxidative coupling products of catechins' A-B ring) were found to be the major chromogenic compounds of EC and C. Additionally, the antioxidant capacity of catechin monomers only decreased after 30-min reaction, while along with further enzymatic reaction, catechin monomers presented comparable oxyradical scavenging ability (e.g., the DPPH inhibitory rates of catechin monomers were in the range of 24.42 %-50.77 %) to vitamin C (positive control, DPPH inhibitory rate was 27.66 %). Meanwhile, the inhibitory effects of most catechin monomers on α-glucosidase were enhanced in different degrees. These results provided basis for the development of enzymatically-oxidized catechin monomers as functional food color additives.

Deep Learning Image Reconstruction for Transcatheter Aortic Valve Implantation Planning: Image Quality, Diagnostic Performance, Contrast volume and Radiation Dose Assessment.

RATIONALE AND OBJECTIVES: To assess image quality, contrast volume and radiation dose reduction potential and diagnostic performance with the use of high-strength deep learning image reconstruction (DLIR-H) in transcatheter aortic valve implantation (TAVI) planning CT. METHODS: We prospectively enrolled 128 patients referred to TAVI-planning CT. Patients were randomly divided into two groups: DLIR-H group (n = 64) and conventional group (n = 64). The DLIR-H group was scanned with tube voltage of 80kVp and body weighted-dependent contrast injection rate of 28mgI/kg/s, images reconstructed using DLIR-H; the conventional group was scanned with 100kVp and contrast injection rate of 40mgI/kg/s, and images reconstructed using adaptive statistical iterative reconstruction-V at 50% (ASIR-V 50%). Radiation dose, contrast volume, contrast injection rate, and image quality were compared between the two groups. The diagnostic performance of TAVI planning CT for coronary stenosis in 115 patients were calculated using invasive coronary angiography as golden standard. RESULTS: DLIR-H group significantly reduced radiation dose (4.94 ± 0.39mSv vs. 7.93 ± 1.20mSv, p < 0.001), contrast dose (45.28 ± 5.38 mL vs. 63.26 ± 9.88 mL, p < 0.001), and contrast injection rate (3.1 ± 0.31 mL/s vs. 4.9 ± 0.2 mL/s, p < 0.001) compared to the conventional group. Images in DLIR-H group had significantly higher SNR and CNR (all p < 0.001). For the diagnostic performance on a per-patient basis, TAVI planning CT in the DLIR-H group provided 100% sensitivity, 92.1% specificity, 100% negative predictive value (NPV), and 84.2% positive predictive value for the detection of > 50% stenosis. In the conventional group, the corresponding results were 94.7%, 95.3%, 97.6%, and 90.0%, respectively. CONCLUSION: DLIR-H in TAVI-planning CT provides improved image quality with reduced radiation and contrast doses, and enables satisfactory diagnostic performance for coronary arteries stenosis.

Ganoderma lucidum-Derived Meroterpenoids Show Anti-Inflammatory Activity In Vitro.

Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.

Tricarboxylic acid cycle metabolites: new players in macrophage.

Metabolic remodeling is a key feature of macrophage activation and polarization. Recent studies have demonstrated the role of tricarboxylic acid (TCA) cycle metabolites in the innate immune system. In the current review, we summarize recent advances in the metabolic reprogramming of the TCA cycle during macrophage activation and polarization and address the effects of these metabolites in modulating macrophage function. Deciphering the crosstalk between the TCA cycle and the immune response might provide novel potential targets for the intervention of immune reactions and favor the development of new strategies for the treatment of infection, inflammation, and cancer.

Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti-PD-1-Based Immunotherapy as Curative-Intent Treatment.

BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.

In Vitro Comparative Analysis of the Effect and Structure-Based Influencing Factors of Flavonols on Lipid Accumulation.

Flavonols represented by quercetin have been widely reported to have biological activities of regulating lipid metabolism. However, the differences in flavonols with different structures in lipid-lowering activity and the influencing factors remain unclear. In this study, the stability, transmembrane uptake ratio, and lipid metabolism regulation activities of 12 flavonol compounds in the 3T3-L1 cell model were systematically compared. The results showed that kaempferide had the highest cellular uptake ratio and the most potent inhibitory effect on adipogenesis at a dosing concentration of 20 µM, followed by isorhamnetin and kaempferol. They inhibited TG accumulation by more than 65% and downregulated the expression of PPARγ and SREBP1c by more than 60%. The other four aglycones, including quercetin, did not exhibit significant activity due to the structural instability in the cell culture medium. Meanwhile, five quercetin glucosides were quite stable but showed a low uptake ratio that no obvious activity was observed. Correlation analysis also showed that for 11 compounds except galangin, the activity was positively correlated with the cellular uptake ratio (p < 0.05, r = 0.6349). These findings may provide a valuable idea and insight for exploring the structure-based activity of flavonoids at the cellular level.

Search for Snail Repellents: Antimollusc Activities from Stemona parviflora and Six Other Chinese Stemona Species.

Snails are important agricultural pests difficult to control, but data regarding molluscicidal assays are scant. Stemona alkaloids are typical secondary metabolites for the taxa and have been broadly investigated for their pharmacological and toxicological effects. This makes it possible for us to further develop the toxicities of these compounds to snails. In this work, we tested the antifeedant properties of leaves from seven Chinese Stemona species against the land snail species Bradybaena ravida in choice and non-choice feeding assays. The tested leaves Stemona parviflora exhibited the most deterrent effects, and a further phytochemical investigation of aerial parts led to the identification of 16 alkaloids. Among them, three novel alkaloids could be identified. The alkaloidal fraction and single alkaloids were further assayed against this snail species, and the results suggest a cocktail effect because the impact of the alkaloidal fraction was higher than the effects caused by single alkaloids. The study can promote the search process of natural antimollusc products from plants to control snails.

Genetic prediction of modifiable lifestyle factors for erectile dysfunction.

Background: The causal relationship between certain lifestyle factors and erectile dysfunction (ED) is still uncertain. Aim: The study sought to investigate the causal effect of 9 life factors on ED through 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR). Methods: Genetic instruments to proxy 9 risk factors were identified by genome-wide association studies. The genome-wide association studies estimated the connection of these genetic variants with ED risk (n = 223 805). We conducted SVMR, inverse variance-weighting, Cochran's Q, weighted median, MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MVMR analyses to explore the total and direct relationship between life factors and ED. Outcomes: The primary outcome was defined as self or physician-reported ED, or using oral ED medication, or a history of surgery related to ED. Results: In SVMR analyses, suggestive associations with increased the risk of ED were noted for ever smoked (odds ratio [OR], 5.894; 95% confidence interval [CI], 0.469 to 3.079; P = .008), alcohol consumption (OR, 1.495; 95% CI, 0.044 to 0.760; P = .028) and body mass index (BMI) (OR, 1.177; 95% CI, 0.057 to 0.268; P = .003). Earlier age at first intercourse was significantly related to reduced ED risk (OR, 0.659; 95% CI, -0.592 to -0.244; P = 2.5 × 10-6). No strong evidence was found for the effect of coffee intake, time spent driving, physical activity, and leisure sedentary behaviors on the incidence of ED (All P > .05). The result of MVMR analysis for BMI (OR, 1.13; 95% CI, 1.01 to 1.25; P = .045) and earlier age at first intercourse (OR, 0.77; 95% CI, 0.56 to 0.99; P = .018) provided suggestive evidence for the direct impact on ED, while no causal factor was detected for alcoholic drinks per week and ever smoked. Clinical implications: This study provides evidence for the impact of certain modifiable lifestyle factors on the development of ED. Strengths and limitations: We performed both SVMR and MVMR to strengthen the causal relationship between exposures and outcomes. However, the population in this study was limited to European ancestry. Conclusion: Ever smoked, alcoholic drinks per week, BMI, and age first had sexual intercourse were causally related to ED, while the potential connection between coffee intake, physical activity, recreational sedentary habits, and increased risk of ED needs to be further confirmed.

A multifunctional dual cation doping strategy to stabilize high-voltage medium-nickel low-cobalt lithium layered oxide cathode.

High-voltage medium-nickel low-cobalt lithium layered oxide cathode materials are intriguing for lithium-ion batteries (LIBs) applications because of their relatively low cost and high capacity. Unfortunately, high charging voltage induces bulk layered structure decline and interface environment deterioration, low cobalt content reduces lithium diffusion kinetics, severely limiting the performance liberation of this kind of cathode. Here, a multifunctional Al/Zr dual cation doping strategy is employed to enhance the electrochemical performance of LiNi0.6Co0.05Mn0.35O2 (NCM) cathode at a high charging cut-off voltage of 4.5 V. On the one hand, Al/Zr co-doping weakens the Li+/Ni2+ mixing through magnetic interactions due to the inexistence of unpaired electrons for Al3+ and Zr4+, thereby increasing the lithium diffusion rate and suppressing the harmful coexistence of H1 and H2 phases. On the other hand, they enhance the lattice oxygen framework stability due to strong Al-O and Zr-O bonds, inhibiting the undesired H2 to H3 phase transition and interface lattice oxygen loss, thereby enhancing the stability of the bulk structure and cathode-electrolyte interface. As a result, Al/Zr co-doped NCM (NCMAZ) shows a 94.2 % capacity retention rate after 100 cycles, while that of NCM is only 79.4 %. NCMAZ also exhibits better rate performance than NCM, with output capacities of 92 mAh/g and 59 mAh/g at a high current density of 5C, respectively. The modification strategy will make the high-voltage medium-nickel low-cobalt cathode closer to practical applications.

Minor ergosteroids and a 19-nor labdane-type diterpenoid with anti-inflammatory effects from Ganoderma lucidum.

A chemical investigation on the fruiting bodies of Ganoderma lucidum led to the isolation and identification of five undescribed ergosteroids including two des-D-steroids (3 and 4) and one rare 6/6/7/5-fused carbon skeletal ergosterol (5) along with one 19-nor labdane-type diterpenoid (6). Their structures including their absolute configurations, were assigned by spectroscopic methods, ECD calculations, and X-ray diffraction analysis. In addition, the anti-inflammatory activities of all the isolates were evaluated. The results indicated that compound 1 can significantly down-regulate the protein expression of iNOS and COX-2 at 20 µM in LPS- stimulated RAW264.7 cells.

Effectiveness, reach, uptake and feasibility of digital health interventions for adults with venous thromboembolism: protocol of a systematic review and meta-analysis.

INTRODUCTION: Prevention of recurrence after an episode of venous thromboembolism (VTE), and also the post-thrombotic syndrome (PTS), is still a recognised challenge. In this meta-analysis, we will summarise existing evidence to compare intelligent system follow-up and routine follow-up for patients with VTE. METHODS AND ANALYSIS: Relevant randomised controlled trials (RCTs) and cohort studies will be included from the following databases: MEDLINE/PubMed, Web of Science and the Cochrane Library. The last search time will be 31 March 2024. Two reviewers will independently identify RCTs and cohort studies according to eligibility and exclusion criteria. The risk of bias of included cohort studies will be assessed with the Newcastle-Ottawa Scale, Methodological Index of Non-Randomised Studies, and the risk of bias of RCTs will be assessed with and Cochrane Collaboration's tool. The primary outcomes include overall survival rate and PTS incidence rate. The Grades of Recommendations, Assessment, Development and Evaluation tool will be used to assess the level of evidence for outcome from RCTs. RevMan V.5.4 software will be used to pool outcomes. ETHICS AND DISSEMINATION: Ethical approval was obtained from Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine Science Research Ethics Committee (SH9H-2023-T466-1). The findings will be disseminated to the public through conference presentations and publication in peer-reviewed scientific journals. PROSPERO REGISTRATION NUMBER: CRD42023410644.