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Introduction: Resident mesenchymal stem cells (MSCs) in the tumor microenvironment play an important role in tumor progression. Up to now, the mechanism of resident MSCs promoting gastric cancer cell migration remains unclear. Methods: We tested the migration ability of gastric cancer cells by transwell assays in this study. The inflammatory factors secreted by MSCs were detected by Luminex and ELISA. The activation of NF-κB signaling was detected by western blot. The exosomes derived from MSCs were isolated and identified by transmission electron microscope, nano-sight and western blot. The expression of miR-374a-5p was confirmed by qRT-PCR and its downstream target HAPLN1 by luciferase reporter assay. The expression of adhesion molecules of gastric cancer cells was detected by flow cytometry. Results: MiR-374a-5p could regulate the expression of inflammatory factors by activating NF-κB signaling. The increase of MCP-1 and the decrease of IFN-γ promoted the migration of gastric cancer cells. The miR-374a-5p in MSCs could be encapsulated and delivered to gastric cancer cells by exosomes derived from MSCs. Exogenous miR-374a-5p up-regulated the expression of adhesion molecules in gastric cancer cells by targeting HAPLN1. And miR-374a-5p-enriched exosomes also promoted the migration of gastric cancer cells. Conclusion: MiR-374a-5p promoted gastric cancer metastasis, and resident MSCs in the gastric cancer microenvironment played a major role in the regulation of gastric cancer metastasis. The study will provide new ideas and potential targets for the prevention and treatment of gastric cancer metastasis.

The neuromodulation effect after ventricular arrhythmia (VA) ablation is unclear. The study aimed to investigate skin sympathetic nerve activity (SKNA) changes in patients receiving catheter ablations for idiopathic VA.Of 43 patients with drug-refractory symptomatic VA receiving ablation, SKNA was continuously recorded for 10 min during resting from electrocardiogram lead I configuration and bipolar electrodes on the right arm 1 day before and 1 day after ablation.Twenty-two patients with acute procedure success and no recurrence during follow-ups were classified as sustained success group (group 1). Other 21 patients were classified as failed ablation group (group 2). Baseline SKNA showed no significant difference between the two groups. Post-ablation SKNA in group 2 was significantly higher than in group 1. In patients with ablation involved right ventricular outflow tract (RVOT), the post-ablation SKNA was also significantly higher in group 2. In contrast, there was no difference in post-ablation SKNA between groups in patients receiving non-RVOT ablation.The neuromodulation response after RVOT ablation may correspond to the sympathetic nerve distribution at RVOT. Augmentation of sympathetic activity after VA ablation indicates an unsuccessful VA suppression, especially in patients receiving ablation of RVOT VA.

A series of 1-[2-(4-methyl-2-(methylthio)pyrimidine-5-carboxamido)phenyl]ethyl-substitutedphenyl carbamates (3a–3i) were designed and synthesized, using 4-methyl-2-(methylthio)pyrimidine-5-carboxylic acid, (2-aminophenyl)ethan-1-one, and substituted phenyl isocyanates as starting materials. Their structures were characterized by 1H NMR, 13C NMR, IR and HRMS. The in vitro fungicidal activities against Sclerotinia sclerotiorum were evaluated, and the result showed that some compounds displayed moderate antifungal activity with >60% inhibitory rates, among which 1-[2-(4-methyl-2-(methylthio)pyrimidine-5-carboxamido)phenyl] ethyl-(2- methyl phenyl)carbamate (3a) and 1-[2-(4-methyl-2-(methylthio)pyrimidine-5- carboxamido)phenyl] ethyl-(3-trifluoromethyl phenyl)carbamate (3g) held inhibitory rates of 69.5% and 70.3% at 100 mg/L, respectively. Molecular docking study showed that 3g can form two hydrogen bonds and a cation-π interaction with succinate dehydrogenase.

China’s power system is highly regulated and uses an “equal-share" dispatch approach. However, market mechanisms are being introduced to reduce generation costs and improve system reliability. Here, we quantify the climate and human health impacts brought about by this transition, modeling China’s power system operations under economic dispatch. We find that significant reductions in mortality related to air pollution (11%) and CO2 emissions (3%) from the power sector can be attained by economic dispatch, relative to the equal-share approach, through more efficient coal-powered generation. Additional health and climate benefits can be achieved by incorporating emission externalities in electricity generation costs. However, the benefits of the transition to economic dispatch will be unevenly distributed across China and may lead to increased health damages in some regions. Our results show the potential of dispatch decision-making in electricity generation to mitigate negative impacts of power plant emissions with existing facilities in China.

Aim. Ulcerative colitis (UC) is a refractory gastrointestinal disease. The study aimed to expound the mechanism of Polygonum bistorta (PB) in treating UC by network pharmacology, molecular docking, and experiment verification. Methods. The compositions and targets of PB and UC-associated targets were obtained by searching the websites and the literature. The potential mechanism of PB in the treatment of UC was predicted by protein-protein interaction network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecule docking was performed by AutoDock. In vitro experiments explored the mechanism of quercetin (Que), the main active composition of PB, in treating UC. Results. Six compositions, 139 PB targets, and 934 UC-associated targets were obtained. 93 overlapping targets between PB and UC were identified, and 18 of them were the core targets. 467 biological processes, 10 cell components, and 30 molecular functions were obtained by GO analysis. 102 pathways were enriched through KEGG analysis. Among them, the IL-17 signaling pathway had high importance. The core targets FOS, JUN, IL-1β, CCL2, CXCL8, and MMP9 could dock with Que successfully. Act1, TRAF6, FOS, and JUN were identified by KEGG as the key proteins of the IL-17 signaling pathway. The expressions of the abovementioned proteins were increased in Caco-2 cells stimulated by Dextran sulfate sodium and decreased after being treated by Que. Conclusion. PB might treat UC by downregulating the IL-17 signaling pathway. It is worth doing further research on PB treating UC in vivo.

Radiofrequency catheter ablation (RFCA) is commonly performed in patients with non-paroxysmal atrial fibrillation (AF), but because very long-term follow-up results of RFCA are limited, we investigated the 10-year RFCA outcomes of non-paroxysmal AF.Methods and Results: We retrospectively enrolled 100 patients (89 men, mean age 53.5±8.4years) with drug-refractory symptomatic non-paroxysmal AF who underwent 3D electroanatomic-guided RFCA. Procedural characteristics at index procedures and clinical outcomes were investigated. In the index procedures, all patients had pulmonary vein isolation, 56 (56.0%), 48 (48.0%), and 32 (32.0%) underwent additional linear, complex fractionated atrial electrogram (CFAE) and non-pulmonary vein (NPV) foci ablations, respectively. After 124.1±31.7 months, 16 (16%) patients remained in sinus rhythm after just 1 procedure (3 with antiarrhythmic drugs [AAD]) and after multiple (2.1±1.3) procedures in 53 (53.0%) patients (22 with AAD). Left atrial (LA) diameter (hazard ratio HR 1.061; 95% confidence interval (CI) 1.020 to 1.103; P=0.003), presence of NPV triggers (HR 1.634; 95% CI 1.019 to 2.623; P=0.042) and undergoing CFAE ablation (HR 2.003; 95% CI 1.262 to 3.180; P=0.003) in the index procedure were independent predictors for recurrent atrial tachyarrhythmia.The 10-year outcomes of single RFCA in non-paroxysmal AF were unsatisfactory. Enlarged LA, presence of NPV triggers, and undergoing CFAE ablation in the index procedure independently predicted single-procedure recurrence. Multiple procedures are required to achieve adequate rhythm control.

Carotid artery stenting (CAS) is an established treatment for local stenosis. The most common complication is new ipsilateral ischemic lesions (NIILs). This study aimed to develop models considering lesion morphological and compositional features, and radiomics to predict NIILs.One hundred and forty-six patients who underwent brain MRI and high-resolution vessel wall MR imaging (hrVWI) before and after CAS were retrospectively recruited. Lumen and outer wall boundaries were segmented on hrVWI as well as atherosclerotic components. A traditional model was constructed with patient clinical information, and lesion morphological and compositional features. Least absolute shrinkage and selection operator algorithm was performed to determine key radiomics features for reconstructing a radiomics model. The model in predicting NIILs was trained and its performance was tested.Sixty-one patients were NIIL-positive and eighty-five negative. Volume percentage of intraplaque hemorrhage (IPH) and patients' clinical presentation (symptomatic/asymptomatic) were risk factors of NIILs. The traditional model considering these two features achieved an area under the curve (AUC) of 0.778 and 0.777 in the training and test cohorts, respectively. Twenty-two key radiomics features were identified and the model based on these features achieved an AUC of 0.885 and 0.801 in the two cohorts. The AUCs of the combined model considering IPH volume percentage, clinical presentation, and radiomics features were 0.893 and 0.842 in the training and test cohort respectively.Compared with traditional features (clinical and compositional features), the combination of traditional and radiomics features improved the power in predicting NIILs after CAS.• Volume percentage of IPH and symptomatic events were independent risk factors of new ipsilateral ischemic lesions (NIILs). • Radiomics features derived from carotid artery high-resolution vessel wall imaging had great potential in predicting NIILs after CAS. • The combination model with radiomics and traditional features further improved the diagnostic performance than traditional features alone.

Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality.To conducted a systematic review and meta-analysis of the prevalence and potential predictors of polymyxin-induced nephrotoxicity in adult intensive care unit (ICU) patients.PubMed, EMBASE, the Cochrane Library and Reference Citation Analysis database were searched for relevant studies from inception through May 30, 2022. The pooled prevalence of polymyxin-induced nephrotoxicity and pooled risk ratios of associated factors were analysed using a random-effects or fixed-effects model by Stata SE ver. 12.1. Additionally, subgroup analyses and meta-regression were conducted to assess heterogeneity.A total of 89 studies involving 12234 critically ill adult patients were included in the meta-analysis. The overall pooled incidence of polymyxin-induced nephrotoxicity was 34.8%. The pooled prevalence of colistin-induced nephrotoxicity was not higher than that of polymyxin B (PMB)-induced nephrotoxicity. The subgroup analyses showed that nephrotoxicity was significantly associated with dosing interval, nephrotoxicity criteria, age, publication year, study quality and sample size, which were confirmed in the univariable meta-regression analysis. Nephrotoxicity was significantly increased when the total daily dose was divided into 2 doses but not 3 or 4 doses. Furthermore, older age, the presence of sepsis or septic shock, hypoalbuminemia, and concomitant vancomycin or vasopressor use were independent risk factors for polymyxin-induced nephrotoxicity, while an elevated baseline glomerular filtration rate was a protective factor against colistin-induced nephrotoxicity.Our findings indicated that the incidence of polymyxin-induced nephrotoxicity among ICU patients was high. It emphasizes the importance of additional efforts to manage ICU patients receiving polymyxins to decrease the risk of adverse outcomes.

Background and ObjectivesMyasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CSs) and IV immunoglobulin (IVIG). This study was conducted to determine whether immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facilitate CS dose reduction in CS-dependent patients with MG.MethodsIn this randomized double-blind placebo-controlled trial, CS-dependent patients with MG (Myasthenia Gravis Foundation of America Class II–Iva; AChR+) received a loading dose of 2 g/kg IGIV-C over 2 days (maximum 80 g/d) or placebo at week 0 (baseline). Maintenance doses (1 g/kg IGIV-C or placebo) were administered every 3 weeks through week 36. Tapering of CS was initiated at week 9 and continued through week 36 unless the patient worsened (quantitative MG score ≥4 points from baseline). CS doses were increased (based on the current CS dose) in patients who worsened. Patients were withdrawn if worsening failed to improve within 6 weeks or if a second CS increase was required. The primary efficacy end point (at week 39) was a ≥50% reduction in CS dose. Secondary and safety end points were assessed throughout the study and follow-up (weeks 42 and 45). The study results and full protocol are available atclinicaltrials.gov/ct2/show/NCT02473965.ResultsThe primary end point (≥50% reduction in CS dose) showed no significant difference between the IGIV-C treatment (60.0% of patients) and placebo (63.3%). There were no significant differences for secondary end points. Safety data indicated that IGIV-C was well tolerated.DiscussionIn this study, IGIV-C was not more effective than placebo in reducing daily CS dose. These results suggest that the effects of IGIV-C and CS are not synergistic and may be mechanistically different.Trial Registration InformationThe trial was registered on clinicaltrialsregister.eu (EudraCT #: 2013-005099-17) andclinicaltrials.gov(identifierNCT02473965).Classification of EvidenceThis study provides Class II evidence that IVIG infusions in adult patients with MG do not increase the percentage of patients achieving a ≥50% reduction in corticosteroid dose compared with placebo.

Arthrobotrys jindingensis and A. tongdianensis, two new species isolated from the freshwater sediment and terrestrial soil in Lanping county, Yunnan, China, are introduced based on morphology and multi-locus phylogenetic analysis (ITS, TEF and RPB2). A. jindingensis is characterized by its branched conidiophores with irregularly swollen nodular apex, pyriform or obovoid, and 1-septate conidia. A. tongdianensis is characterized by its branched conidiophores, and ellipsoid or obovate, 1-septate conidia. Phylogenetic analysis supports them as two new species within Arthrobotrys with high support. The descriptions and illustrations of these two species are provided in this paper.

The recent Atrial Fibrillation Management in Congestive Heart Failure With Ablation (AMICA) trial did not reveal any benefit of catheter ablation in patients with atrial fibrillation (AF), advanced heart failure (HF), and severely reduced left ventricular ejection fraction (LVEF). We hypothesized that radiofrequency catheter ablation (RFCA) could improve outcomes in HF patients with AF and impaired left ventricular systolic function (LVEF50%) as compared with only medical therapy.We searched the literature for randomized clinical trials (RCTs) that compared RFCA to medical therapy in this population.Compared with the medical therapy group, the RFCA group had significantly less all-cause mortality, HF hospitalization, and AF recurrence rates. The RFCA group had significantly higher peak oxygen consumption (VO 2 max), a better quality of life (Minnesota Living with Heart Failure Questionnaire score), and improved LVEF. However, RFCA for AF failed to reduce all-cause mortality in a specific meta-analysis of four RCTs that enrolled patients with LVEF ≤35%.Compared with medical therapy, RFCA for AF in the setting of HF with impaired systolic function is associated with better clinical (HF hospitalization and all-cause mortality), structural (LVEF improvement), functional (VO 2 max), and quality of life outcomes. However, RFCA for AF failed to reduce all-cause mortality in RCTs that enrolled patients with LVEF ≤35%, and thereby indicated the necessary stratification to identify patients who may benefit more from RFCA.

The efficacy of catheter ablation (CA) on clinical outcomes and cardiac structural remodelling in atrial fibrillation (AF) patients with HF with mildly reduced or mid-range ejection fraction (HFmrEF) remains unclear. We aimed to compare the efficacy of CA with medical therapy (MT) in AF patients with HFmrEF.We retrospectively screened a total of 36 879 patients with AF between 2005 and 2020. Patients who were initially diagnosed with echocardiography-proved HFmrEF and had follow-up echocardiography were enrolled. After applying propensity score matching in a 1:1 ratio, 72 patients treated by CA (Group 1) and 72 patients receiving MT (Group 2) were taken into further analysis. The co-morbidities were similar between the two groups, except for hyperlipidaemia. After a mean follow-up duration of 58.9 ± 42.6 months, Group 1 had a lower HF hospitalization and all-cause mortality compared with Group 2 (hazard ratio (HR), 0.089 [95% confidence interval (CI), 0.011-0.747]; P = 0.026 and HR, 0.121 [95% CI, 0.016-0.894]; P = 0.038, respectively). As for cardiac structural remodelling, the Group 1 had a better improvement in left ventricular ejection fraction (LVEF) and a more decreased left atrium (LA) diameter than Group 2 (+25.0% ± 18.0% vs. +6.2% ± 21.6%, P = 0.0001 and -1.6 ± 4.7 mm vs. +1.5 ± 8.2 mm, P = 0.008, respectively).In patients with HFmrEF and AF, CA of AF could reduce both HF hospitalization and all-cause mortality as compared with those with MT. A significant improvement in LVEF and decrease in LA diameter were also observed in the CA group. Early rhythm control with CA should be taken into consideration in patients with HFmrEF and AF.

Blood pressure variability (BPV) is independently associated with higher cardiovascular risks. However, whether BPV is associated with poor outcomes for coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remained undetermined. We aimed to investigate the relationship between BPV and the outcomes of CAD patients undergoing PCI. Two thousand seven hundred and sixty-two CAD patients (1938 males, mean age 69.6 ± 12.9) who received PCI at Taipei Veterans General Hospital from 2006 to 2015 with multiple blood pressure measurements before and after the index PCI were enrolled. We calculated the standard deviation of systolic blood pressure, diastolic blood pressure, and pulse pressure as parameters of BPV. The primary endpoint was the composite of major adverse cardiovascular events [MACE comprising of cardiovascular death, nonfatal myocardial infarction (MI), and non-fatal stroke] and heart failure hospitalization (HHF). The key secondary endpoint was MACE. Both pre-PCI and post-PCI BPV were associated with CV events even after adjusting for co-morbidities and mean blood pressure. In Cox analysis, for every 1 mmHg increase in systolic BPV, the hazard ratio for the MACE + HHF, MACE, HHF, and cardiovascular death was 1.04 (95%CI: 1.03-1.05), 1.04 (95%CI: 1.02-1.05), 1.05 (95%CI: 1.04-1.06), and 1.06 (95%CI: 1.03-1.09), respectively. The association between BPV and cardiovascular risk is independent of blood pressure control status. The prognostic value of BPV was superior to mean blood pressure in both pre-PCI and post-PCI period. BPV is independently associated with cardiovascular events after PCI and has a better prognostic value than mean blood pressure suggesting the importance of maintaining stable blood pressure for CAD patients.

To evaluate the prognostic value of aortic distensibility measured by cardiovascular magnetic resonance (CMR) as predictors of prophylactic aortic valve or aortic surgery in patients with bicuspid aortic valve (BAV). 110 patients with BAV were included. Distensibility of middle ascending aorta (AscAo) and proximal descending aorta (DescAo) at baseline was determined using CMR. The association between aortic distensibility and primary endpoint of aortic valve and/or aortic surgery was investigated with Cox proportional hazard regression analyses. The receiver operating characteristics curves (ROC) of the area under receiver-operator (AUC) and DeLong test were used to evaluate and compare the performance of different models. During a median follow-up of 66.5 months [IQR 13-75 months], 42 patients experienced surgical treatments. After adjusting for traditional risk factors, aortic distensibility (P = 0.003) and severe valve dysfunction (P 0.001) were found significantly associated with aortic valve and/or aortic surgery. The model 2 (aortic distensibility and severe valve dysfunction) is slightly better in predicting primary endpoint than the model 1 (aortic diameter and severe valve dysfunction) (AUC: 0.893 vs. 0.842, P = 0.106). In BAV patients, aortic distensibility and severe valve dysfunction are valuable predictors for final aortic valve and/or aortic surgery.

This study is an investigation into the inhibitory effect of seawater pearl hydrolysate (SPH) on the UVA-induced photoaging of human skin fibroblast (HSF) cells, and the mechanism thereof. HSF cells were cultured and irradiated with a UVA 0–50 J·cm−2 dose gradient. The cell inhibition rate was detected using the CCK8 method, and the half-inhibitory dose was determined. Based on this, the dose of UVA irradiation for the follow-up experiment was selected to establish a photoaging model of the HSF cells. The cells were divided into a normal (N) group, UVA-irradiated (UVA) group, SPH low dose (SPHL) group, SPH medium dose (SPHM) group, and SPH high dose (SPHH) group. The photoaging model of HSF cells was established by UVA irradiation in the UVA, SPHL, SPHM, and SPHH groups; the SPHL, SPHM, and SPHH groups were treated with SPH at concentrations of 50, 100, and 200 mg·L−1, respectively, at the same time. After 24 and 48 h of culture, the reactive oxygen species (ROS) level of the HSF cells was detected by flow cytometry, and the required culture time of the HSF cells for the follow-up experiment was selected. The malondialdehyde and glutathione contents, as well as the activities of the superoxide dismutase, catalase, and glutathione peroxidase in the HSF cells, were detected by biochemical methods. The levels of expression of MMP-1 and collagen I protein in HSF cells were detected by the western blot test, the extent of aging of HSF cells was detected by β-galactosidase staining, and the apoptosis level of HSF cells was detected by flow cytometry. The results show that SPH inhibits the UVA-induced photoaging of HSF cells in a dose-dependent manner within a certain concentration range, and the effect of a concentration of 200 mg·L–1 was the most significant. The mechanism is related to improving the antioxidant activity of photoaging HSF cells to eliminate excessive ROS. It can inhibit apoptosis, reduce the protein expression of MMP-1, and effectively control the degradation of collagen I protein in photoaging HSF cells. Therefore, SPH offers potential for use in sunscreen cosmetics.

The control rate of hypertension remains concerning, indicating the requirement for better management strategies. The calcium channel blockers brand-name amlodipine and nifedipine with extended-release formulations demonstrate similar clinical efficacy. However, the efficacy of generic nifedipine remains obscure. We compared the efficacy of generic nifedipine and brand-name amlodipine in terms of cardiovascular (CV) outcomes. Patients prescribed generic nifedipine (SRFC CYH) or brand-name amlodipine besylate (Norvasc, Pfizer) between August 1, 2017, and July 31, 2018, were enrolled; patients with CV events within 3 months were excluded. CV outcomes included CV death, nonfatal myocardial infarction (MI), nonfatal ischemic stroke, hospitalization for heart failure, and composite endpoints of 3P- and 4P-major adverse cardiac events (MACE). A total of 1625 patients treated with nifedipine (SRFC CYH) and 16 587 patients treated with Norvasc were included. After propensity score matching, there were 995 and 4975 patients in the nifedipine CYH and Norvasc groups, respectively. At a mean follow-up period of 30.3 ± 6.4 months, nifedipine CYH was comparable to Norvasc in terms of CV death (P = .107), nonfatal MI (P = .121), nonfatal ischemic stroke (P = .453), hospitalization for heart failure (P = .330), 3P-MACE (P = .584), and 4P-MACE (P = .274). Cox regression analysis revealed that nifedipine CYH and Norvasc had similar efficacy in terms of 3P-MACE (hazard ratio, 0.970; 95% confidence interval, 0.601-1.565, P = .900) and 4P-MACE (hazard ratio, 0.880; 95% confidence interval, 0.628-1.233, P = .459). In conclusion, Nifedipine SRFC CYH and Norvasc have comparable clinical efficacy for hypertension management.

The problem of bilateral matching of teams and scientific and technical talents is studied in new R&D institutions with different forms of uncertain assessment information. A decision method is proposed based on a combination of grey correlation and cloud model. The method firstly applies interval grey numbers to characterize uncertain assessment score information and cloud models to characterize uncertain linguistic assessment information; secondly, the two different pieces of information are converted into grey correlation coefficients by applying grey correlation analysis methods to the assessment values, so as to solve indicator weights, and assemble assessment data based on indicator weights and cloud models; finally, the bilateral matching model is constructed and the matching results are solved based on the cloud model data features and the dual objectives of maximum satisfaction and minimum uncertainty. The case analysis and method comparison show that the method is feasible and effective.

Renal denervation (RDN) suppresses the activity of the renin–angiotensin–aldosterone system and inflammatory cytokines, leading to the prevention of cardiac remodeling. Limited studies have reported the effects of renal denervation on ventricular electrophysiology. We aimed to use optical mapping to evaluate the effect of RDN on ventricular structural and electrical remodeling in a tachycardia-induced cardiomyopathy rabbit model. Eighteen rabbits were randomized into 4 groups: sham control group (n = 5), renal denervation group receiving RDN (n = 5), heart failure group receiving rapid ventricular pacing for 1 month (n = 4), and RDN-heart failure group (n = 4). Rabbit hearts were harvested for optical mapping. Different cycle lengths were paced (400, 300, 250, 200, and 150 ms), and the results were analyzed. In optical mapping, the heart failure group had a significantly slower epicardial ventricular conduction velocity than the other three groups. The RDN-heart failure, sham control, and RDN groups had similar velocities. We then analyzed the 80% action potential duration at different pacing cycle lengths, which showed a shorter action potential duration as cycle length decreased (P for trend P

Single-cell transcriptomics analysis is an advanced technology that can describe the intracellular transcriptome in complex tissues. It profiles and analyses datasets by single-cell RNA sequencing. Neurodegenerative diseases are identified by the abnormal apoptosis of neurons in the brain with few or no effective therapy strategies at present, which has been a growing healthcare concern and brought a great burden to society. The transcriptome of individual cells provides deep insights into previously unforeseen cellular heterogeneity and gene expression differences in neurodegenerative disorders. It detects multiple cell subsets and functional changes during pathological progression, which deepens the understanding of the molecular underpinnings and cellular basis of neurodegenerative diseases. Furthermore, the transcriptome analysis of immune cells shows the regulation of immune response. Different subtypes of immune cells and their interaction are found to contribute to disease progression. This finding enables the discovery of novel targets and biomarkers for early diagnosis. In this review, we emphasize the principles of the technology, and its recent progress in the study of cellular heterogeneity and immune mechanisms in neurodegenerative diseases. The application of single-cell transcriptomics analysis in neurodegenerative disorders would help explore the pathogenesis of these diseases and develop novel therapeutic methods.

BackgroundCatheter ablation (CA) is a treatment strategy for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). We investigated the electrophysiological characteristics of recurrence in a tertiary referral center and compared long-term clinical outcomes after CA therapy with patients who did not undergo CA.MethodsPatients with HCM and AF who underwent CA (group 1, n = 60) or pharmacological treatment (group 2, n = 298) between 2006 and 2021 were enrolled in this study. The baseline characteristics and electrophysiological characteristics of group 1 patients were examined to elucidate the reason for the recurrence of AF after CA therapy. The clinical results of the patients in Group 1 and Group 2 were compared using a propensity score (PS)-matched method.ResultsThe most common cause of recurrence was pulmonary vein reconnection (86.5%), followed by non-pulmonary vein triggers (40.5%), cavotricuspid isthmus flutter (29.7%), and atypical flutter (24.3%). Thyroid disease (HR, 14.713; P P = 0.03), and non-paroxysmal AF (HR, 4.012; P = 0.01); these factors independently predicted recurrence. After the first recurrence, patients who underwent repeat CA showed a better arrhythmia-free state (74.1%) than those who underwent drug escalation therapy (29.4%, P ConclusionsPatients who underwent CA showed better clinical outcomes than those who underwent drug therapy. The main predictors of recurrence were thyroid disease, diabetes, and non-paroxysmal AF.

Diabetic retinopathy (DR) is one of the leading causes of blindness. Periodontitis is one of the highest oral incidences and has been closely related to various systemic conditions through Porphyromonas gingivalis (P. gingivalis). P. gingivalis OMVs, derived from P. gingivalis, can cause endothelial dysfunction and potentially affect microvascular diseases. Current epidemiological studies provide limited evidence suggesting that periodontitis is associated with DR. However, there is a lack of basic research elucidating how periodontitis affects the severity of DR. This study aimed to explore the potential of P. gingivalis OMVs to contribute to the pathogenesis of DR and explore how it affect the retinal microvascular endothelium. The results demonstrated that P. gingivalis OMVs accelerated the blood-retinal barrier damage in DR mice. In vitro studies showed that the expression of inflammatory factors in human retinal microvascular endothelial cells (HRMECs) was increased after P. gingivalis OMVs stimulation, and the increased reactive oxygen species production, mitochondrial dysfunction, apoptosis, and altered endothelial permeability were observed in HRMECs under P. gingivalis OMVs stimulation. In addition, we found that protease-activated receptor-2 (PAR-2) regulated OMVs-induced TNF-α, MMP-9 mRNA expression, cell death, and endothelial permeability. Overall, we suggested that P. gingivalis OMVs induced mitochondria-related cell death of HRMECs and accelerated endothelial dysfunction, thus aggravating DR, in which PAR-2 plays a potential role. This study is the first research report to delineate the potential molecular mechanism of P. gingivalis OMVs on DR pathogenesis, which uniquely focused on elucidating the possible impact of periodontal pathogen derivatives on DR progression.

BackgroundPreoperative measurements of left atrium (LA) and epicardial adipose tissue (EAT) volumes in computed tomography (CT) images have been reported to be associated with an increased risk of atrial fibrillation (AF) recurrence. We aimed to design a deep learning-based workflow to provide a reliable automatic segmentation of atria, pericardium and EAT, which can facilitate future applications in AF.MethodsA total of 157 patients with AF who underwent radiofrequency catheter ablation were enrolled in this study. The 3D U-Net models of LA, right atrium (RA) and pericardium were used to develop the pipeline of total, LA-and RA-EAT automatic segmentation. We defined the attenuation range between -190 to -30 HU as fat within the pericardium to obtain total EAT. Regions between the dilated endocardial boundaries and endocardial walls of LA or RA within the pericardium were used to detect the voxels attributed to fat, resulting in LA-EAT and RA-EAT.ResultsThe LA, RA and pericardium segmentation models achieved Dice coefficients of 0.960 ± 0.010, 0.945 ± 0.013 and 0.967 ± 0.006, respectively. The 3D segmentation models correlated well with ground truth for LA, RA and pericardium (r=0.99 and p < 0.001 for all). For the results of EAT, LA-EAT and RA-EAT segmentation, Dice coefficients of our proposed method were 0.870 ± 0.027, 0.846 ± 0.057 and 0.841 ± 0.071, respectively.ConclusionsOur proposed workflow for automatic LA/RA and EAT segmentation applying 3D U-Nets on CT images was reliable in patients with AF.

Aims This study investigated the epidemiological characteristics of new-onset dementia in patients with atrial fibrillation (AF) and the association of catheter ablation with different subtypes of dementia. Methods and results We conducted a population-based, retrospective cohort study using data from the Taiwan National Health Insurance Research Database. In total, 136 774 patients without a history of dementia were selected after 1:1 propensity score matching based on age (with AF vs. without AF). A competing risk model was used to investigate the three subtypes of dementia: Alzheimer’s disease, vascular dementia, and other/mixed dementia. Inverse probability of treatment weighting (IPTW) was performed to minimize the impact on dementia risk due to the imbalanced baseline characteristics. After a median follow-up period of 6.6 years, 8704 events of new-onset dementia occurred. Among all AF patients developing dementia, 73% were classified as having Alzheimer’s disease, 16% as having vascular dementia, and 11% as having other/mixed dementia. The cumulative incidence of dementia in AF patients was higher than those without AF (log-rank test: P < 0.001 for both before and after IPTW). In patients with AF undergoing catheter ablation, the total dementia risk decreased significantly [P = 0.015, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.58–0.94] after multivariable adjustment, but not for the subtype of vascular dementia (P = 0.59, HR: 0.86, 95% CI: 0.49–1.50). Conclusion Patients with AF have a higher incidence of all types of dementia, including Alzheimer’s disease, vascular dementia, and a mixed type of dementia. Alzheimer’s disease is less likely to occur in patients with AF undergoing catheter ablation.

BackgroundKnowledge of the risk of death in patients with dementia is essential for planning preventive strategies. This study aimed to evaluate the effect of atrial fibrillation (AF) on death risks and other factors associated with death in patients with dementia and AF.MethodsWe conducted a nationwide cohort study using Taiwan's National Health Insurance Research Database. We identified subjects with dementia diagnosed for the first time and AF diagnosed concomitantly between 2013 and 2014. Subjects under the age of 18 years were excluded. Age, sex, and CHA2DS2-VASc scores were 1: 4 matched for AF patients (N = 1,679) and non-AF controls (N = 6,176) using the propensity score technique. The conditional Cox regression model and competing risk analysis were applied. The risk of mortality was tracked till 2019.ResultsAF history was associated with higher risks of all-cause death (hazard ratio [HR]: 1.208; 95% confidence interval [CI]: 1.142–1.277) and cardiovascular death (subdistribution HR: 1.210; 95% CI: 1.077–1.359) in dementia patients than patients without a diagnosis of AF. For patients with both dementia and AF, they had a higher risk of death due to higher age, diabetes mellitus, congestive heart failure, chronic kidney disease, and prior stroke. Anti-arrhythmic drugs and novel oral anticoagulants significantly reduced the risk of death in patients with AF and dementia.ConclusionThis study found that AF is a risk factor for mortality in patients with dementia and explored several risk factors for AF-related mortality. This study highlights the importance of controlling AF especially in patients with dementia.

Background The microbiome plays a crucial role in Odontogenic sinusitis (OS); however, bacterial characteristics of the sinuses and connected dental regions in OS are poorly understood. In this study, nasal secretion were collected from 41 OS patients and 20 simple nasal septum deviation patients, and oral mucosa samples from dental regions were collected from 28 OS patients and 22 impacted teeth extraction patients. DNA was extracted and 16S rRNA sequencing was performed to explore the characteristics and structure of microbiome in sinuses and dental regions of OS patients. Results Alpha diversity of oral and nasal microbiome in OS patients all were higher than that in control. Principal co-ordinates analysis (PCoA) showed that oral samples clustered separately from nasal samples, beta diversity of oral and nasal samples in OS patients were also higher than that in control. Dominant phylum was Bacteroidota in OS patients and Firmicutes in control, either in oral or nasal cavity. Dominant genera in oral microbiome of OS patients were similar to that of control, were Fusobacterium, Porphyromonas and Prevotella, which were close to nasal microbiome structure of OS, while dominant genus in nasal microbiome of control were Staphylococcus, Corynebacterium and Cutibacterium. Co-occurrence network analysis showed decreased microbial connectivity in oral mucosa and nasal secretion samples of OS patients. Conclusions Odontogenic infection promotes structural and functional disorders of nasal microbiome in OS. The interaction of dominant pathogens in nasal and oral regions may promote the development of OS. Our study provides the microbiological aetiology of the nasal and connected dental regions in OS and is expected to provide novel insights into the diagnosis and therapeutic strategies for OS.

CD300s are a group of proteins playing vital roles in immune responses. However, much is yet to be elucidated regarding the expression patterns and clinical significances of CD300s in cancers.In this study, we comprehensively investigated CD300s in a pan-cancer manner using multi-omic data from The Cancer Genome Atlas. We also studied the relationship between CD300s and the immune landscape of AML.We found that CD300A-CD300LF were generally overexpressed in tumors (especially AML), whereas CD300LG was more often downregulated. In AML, transactivation of CD300A was not mediated by genetic alterations but by histone modification. Survival analyses revealed that high CD300A-CD300LF expression predicted poor outcome in AML patients; the prognostic value of CD300A was validated in seven independent datasets and a meta dataset including 1115 AML patients. Furthermore, we demonstrated that CD300A expression could add prognostic value in refining existing risk models in AML. Importantly, CD300A-CD300LF expression was closely associated with T-cell dysfunction score and could predict response to AML immunotherapy. Also, CD300A was found to be positively associated with HLA genes and critical immune checkpoints in AML, such as VISTA, CD86, CD200R1, Tim-3, and the LILRB family genes.Our study demonstrated CD300s as potential prognostic biomarker and an ideal immunotherapy target in AML, which warrants future functional and clinical studies.

The presence of bipolar low-voltage zone (LVZ) is a predictor of AF recurrence after PV isolation (PVI). However, changes of wavefront and bipole directions may cause different electrogram characteristics. We aimed to investigate whether using omnipolar maximum voltage (Vmax) map derived from high density (HD) Grid mapping catheter could assess LVZ and AF ablation outcome accurately.Fifty paroxysmal AF patients (27 males, 57.8 ± 9.5 years old) who underwent 3D mapping guided PVI were enrolled. Left atrial voltage mapping during sinus rhythm before ablation was performed. The significant LVZ (0.5 mV with area 5 cmPVI was performed in all patients, and there were 2 patients (4%) who also received additional non-PV triggers ablation. After a follow-up of 11.4 ± 5.4 months, recurrence of AF occurred in 12 patients (24%). The presence of a significant LVZ was less detected by omnipolar Vmax map, compared to HD wave map (24.0% vs. 58.0%, p = 0.001). LVZ detected by omnipolar Vmax map independently predicted the AF recurrence (odds ratio 16.91; 95% CI, 3.17-90.10; p = 0.001).LVZ detected by omnipolar Vmax map accurately predicts the AF recurrence following ablation in paroxysmal AF, compared to conventional bipolar and HD wave maps, suggesting the omnipolar Vmax map can precisely define the atrial substrate property.

Since the outer surface interaction of Q[n]s (OSIQ, including self-, anion- and aromatic-induced OSIQs) was proposed in 2014, it has become the most important research area in our group to construct various Q[n]-based supramolecular frameworks via the OSIQ strategy. Herein, we report a novel supramolecular framework constructed using cucurbit[8]uril (Q[8]) and 4-sulfocalix[6]arene (SC[6]A). This Q[8]/SC[6]A-based supramolecular framework is a product via the perfect combination of self-, anion- and aromatic-induced OSIQs. This framework has the characteristics of easy preparation and high stability with the most important feature being the sequence selective capture of specific metal cations, such as common alkali- and alkaline earth metal ions, and renewability. Thus, this framework may be used in seawater desalination, potassium ion enrichment, radioactive cesium ion pollution source treatment, Gruinard's treatment or water softening and other applications.

RNA-based therapy is a promising and potential strategy for disease treatment by introducing exogenous nucleic acids such as messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) or antisense oligonucleotides (ASO) to modulate gene expression in specific cells. It is exciting that mRNA encoding the spike protein of COVID-19 (coronavirus disease 2019) delivered by lipid nanoparticles (LNPs) exhibits the efficient protection of lungs infection against the virus. In this review, we introduce the biological barriers to RNA delivery in vivo and discuss recent advances in non-viral delivery systems, such as lipid-based nanoparticles, polymeric nanoparticles, N-acetylgalactosamine (GalNAc)-siRNA conjugate, and biomimetic nanovectors, which can protect RNAs against degradation by ribonucleases, accumulate in specific tissue, facilitate cell internalization, and allow for the controlled release of the encapsulated therapeutics., Graphical abstract Unlabelled Image