Ultralight Electrolyte with Protective Encapsulation Solvation Structure Enables Hybrid Sulfur-Based Primary Batteries Exceeding 660 Wh/kg.

An electrochemical couple of lithium and sulfur possesses the highest theoretical energy density (>2600 Wh/kg) at the material level. However, disappointingly, it is out of place in primary batteries due to its low accessible energy density at the cell level (≤500 Wh/kg) and poor storage performance. Herein, a low-density methyl tert-butyl ether was tailored for an ultralight electrolyte (0.837 g/mL) with a protective encapsulation solvation structure which reduced electrolyte weight (23.1%), increased the utilization of capacity (38.1%), and simultaneously forfended self-discharge. Furthermore, active fluorinated graphite partially replaced inactive carbon to construct a hybrid sulfur-based cathode to bring the potential energy density into full play. Our demonstrated pouch cell achieved an incredible energy density of 661 Wh/kg with a negligible self-discharge rate based on the above innovations. Our work is anticipated to provide a new direction to realize the practicality of lithium-sulfur primary batteries.

Comparison of downsizing strategy (HANGZHOU Solution) and standard annulus sizing strategy in type 0 bicuspid aortic stenosis patients undergoing transcatheter aortic valve replacement: Rationale and design of a randomized clinical trial.

BACKGROUND: There has not been a consensus on the prothesis sizing strategy in type 0 bicuspid aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR). Modifications to standard annular sizing strategies might be required due to the distinct anatomical characteristics. We have devised a downsizing strategy for TAVR using a self-expanding valve specifically for patients with type 0 bicuspid AS. The primary aim of this study is to compare the safety and efficacy of downsizing strategy with the Standard Annulus Sizing Strategy in TAVR for patients with type 0 bicuspid AS. TRIAL DESIGN: It is a prospective, multi-center, superiority, single-blinded, randomized controlled trial comparing the Down Sizing and Standard Annulus Sizing Strategy in patients with type 0 bicuspid aortic stenosis undergoing transcatheter aortic valve replacement. Eligible participants will include patients with severe type 0 bicuspid AS, as defined by criteria such as mean gradient across aortic valve ≥40 mmHg, peak aortic jet velocity ≥4.0 m/s, aortic valve area (AVA) ≤1.0 cm², or AVA index ≤0.6 cm2/m2. These patients will be randomly assigned, in a 1:1 ratio, to either the Down Sizing Strategy group or the Standard Sizing Strategy group. In the Down Sizing Strategy group, a valve one size smaller will be implanted if the "waist sign" manifests along with less than mild regurgitation during balloon pre-dilatation. The primary end point of the study is a composite of VARC-3 defined device success, absence of both permanent pacemaker implantation due to high-degree atrioventricular block and new-onset complete left bundle branch block. CONCLUSION: This study will compare the safety and efficacy of Down Sizing Strategy with the Standard Annulus Sizing Strategy and provide valuable insights into the optimal approach for sizing in TAVR patients with type 0 bicuspid AS. We hypothesize that the Down Sizing Strategy will demonstrate superiority when compared to the Standard Annulus Sizing Strategy. (Down Sizing Strategy (HANGZHOU Solution) vs Standard Sizing Strategy TAVR in Bicuspid Aortic Stenosis (Type 0) (TAILOR-TAVR), NCT05511792).

A modified Carpentier classification in transcatheter edge-to-edge repair for mitral regurgitation.

Mitral regurgitation (MR) is the most common heart valve disease, and transcatheter edge-to-edge repair (TEER) has been recommended as a therapy for severe MR patients by guidelines. The classic Carpentier classification used to guide surgical mitral valve repair but is inadequate for mitral TEER (M-TEER). We herein proposed a new modified Carpentier classification named after "type + segment," which is suitable for M-TEER. We shared our strategies in M-TEER procedure for screening and performing the M-TEER according to the new modified Carpentier classification.

Mechanical study of alisol B 23-acetate on methionine and choline deficient diet-induced nonalcoholic steatohepatitis based on untargeted metabolomics.

Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.

Smartwatch-Detected Arrhythmias in Patients After Transcatheter Aortic Valve Replacement (TAVR): Analysis of the SMART TAVR Trial.

BACKGROUND: There are limited data available on the development of arrhythmias in patients at risk of high-degree atrioventricular block (HAVB) or complete heart block (CHB) following transcatheter aortic valve replacement (TAVR). OBJECTIVE: This study aimed to explore the incidence and evolution of arrhythmias by monitoring patients at risk of HAVB or CHB after TAVR using smartwatches. METHODS: We analyzed 188 consecutive patients in the prospective SMART TAVR (smartwatch-facilitated early discharge in patients undergoing TAVR) trial. Patients were divided into 2 groups according to the risk of HAVB or CHB. Patients were required to trigger a single-lead electrocardiogram (ECG) recording and send it to the Heart Health App via their smartphone. Physicians in the central ECG core lab would then analyze the ECG. The incidence and timing of arrhythmias and pacemaker implantation within a 30-day follow-up were compared. All arrhythmic events were adjudicated in a central ECG core lab. RESULTS: The mean age of the patients was 73.1 (SD 7.3) years, of whom 105 (55.9%) were men. The mean discharge day after TAVR was 2.0 (SD 1.8) days. There were no statistically significant changes in the evolution of atrial fibrillation or atrial flutter, Mobitz I, Mobitz II, and third-degree atrial ventricular block over time in the first month after TAVR. The incidence of the left bundle branch block (LBBB) increased in the first week and decreased in the subsequent 3 weeks significantly (P<.001). Patients at higher risk of HAVB or CHB received more pacemaker implantation after discharge (n=8, 9.6% vs n=2, 1.9%; P=.04). The incidence of LBBB was higher in the group with higher HAVB or CHB risk (n=47, 56.6% vs n=34, 32.4%; P=.001). The independent predictors for pacemaker implantation were age, baseline atrial fibrillation, baseline right bundle branch block, Mobitz II, and third-degree atrioventricular block detected by the smartwatch. CONCLUSIONS: Except for LBBB, no change in arrhythmias was observed over time in the first month after TAVR. A higher incidence of pacemaker implantation after discharge was observed in patients at risk of HAVB or CHB. However, Mobitz II and third-degree atrioventricular block detected by the smartwatch during follow-ups were more valuable indicators to predict pacemaker implantation after discharge from the index TAVR. TRIAL REGISTRATION: ClinicalTrials.gov NCT04454177; https://clinicaltrials.gov/study/NCT04454177.

China special issue on gastrointestinal tumors-Cetuximab retreatment plus camrelizumab and liposomal irinotecan in patients with RAS wild-type metastatic colorectal cancer: Cohort B of the phase II CRACK study.

Patients with metastatic colorectal cancer (mCRC) have poor long-term survival. Rechallenge with anti-epidermal growth factor receptor (anti-EGFR) based therapy has shown certain activity as late-line therapy. To further improve clinical outcomes, we evaluated the antitumor efficacy and safety of cetuximab in combination with camrelizumab and liposomal irinotecan in patients with RASwt mCRC pretreated with anti-EGFR-based therapy. Patients with RASwt mCRC who had received at least two prior systemic therapies, including anti-EGFR-based treatment in the metastatic or unresectable disease setting, were enrolled in cohort B. Patients were treated with cetuximab (500 mg/m2 ) and camrelizumab (200 mg) plus liposomal irinotecan (HR070803, 60 mg/m2 ) intravenously once every 2 weeks. The primary endpoint was the objective response rate (ORR) by RECIST v1.1. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. At the data cutoff (23 November 2022), 19 patients were enrolled in the two stages, and 16 were evaluable for efficacy analyses. The ORR was 25% (95% confidence interval [CI]: 10.2%-49.5%), and DCR was 75% (95% CI: 50.5%-89.8%). The median PFS and OS were 6.9 (95% CI: 2.6-11.2) and 15.1 (95% CI: 6.1-24.0) months, respectively. Grade 3 treatment-related adverse events (TRAEs) occurred in 15.8% (3/19) of patients. No grade ≥4 TRAEs were found in the safety population. Our study suggests that anti-EGFR retreatment therapy with cetuximab plus camrelizumab and liposomal irinotecan (HR070803) is a promising late-line treatment option with good antitumor activity and well-tolerated toxicity in RASwt mCRC patients.

The gut microbiome: an important factor influencing therapy for pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most prevalent form of pediatric leukemia. The gut microbiome (GM) is crucial for proper nutrition, immunity, and biological conflict. Since the relationship between ALL and GM is bidirectional, ALL occurrence and treatment are closely related to GM destruction and the development of impaired immunity. Studies have discovered significant GM alterations in patients with ALL, including decreased diversity, that are likely directly caused by the development of ALL. Chemotherapy, antibiotic therapy, and hematopoietic stem cell transplantation (HSCT) are the mainstays of treatment for pediatric ALL. These approaches affect the composition, diversity, and abundance of intestinal microorganisms, which in turn affects therapeutic efficiency and can cause a variety of complications. Modulating the GM can aid the recovery of patients with ALL. This article discusses the various treatment modalities for pediatric ALL and their corresponding effects on the GM, as well as the changes in the GM that occur in children with ALL from diagnosis to treatment. Gaining a greater understanding of the link between ALL and the GM is expected to help improve treatment for pediatric ALL in the future.

The role of flexible bronchoscopy in children with Mycoplasma pneumoniae pneumonia.

PURPOSE: To explore the effectiveness of flexible bronchoscopy in pediatric Mycoplasma pneumoniae pneumonia (MPP). METHODS: This retrospective cohort study included children with MPP admitted between 2016 and 2019 in Shanghai. Tracheobronchial manifestations, etiologic findings, therapeutic effect, and health-economic indicators were assessed in bronchoscopy (plus bronchoalveolar lavage (BAL)) and non-bronchoscopy group. We used propensity-score matching and multivariable logistic regression to investigate the effect of bronchoscopy and BAL on disease recovery. RESULTS: In 900 children with MPP, 24/278 (8.6%) of those who underwent bronchoscopy had sputum plugs. Coinfection rate was four-fold enhanced by BAL (19.6% vs. 4.5%, p < 0.01) in patients with severe MPP (SMPP) and nearly doubled (10.8% vs. 5.9%, p = 0.03) in those without SMPP, compared with no BAL. Total of 224 (24.9%) patients had multilobar consolidation; after BAL, a significantly shorter lesion-resolution duration was observed on imaging (OR: 0.2, 95% CI: 0.0-0.7). However, longer fever duration (OR: 2.8, 95% CI: 1.7-4.8), hospital stay (OR: 3.1, 95% CI: 1.9-5.1), and higher costs were found in the bronchoscopy group than in the non-bronchoscopy group. CONCLUSIONS: Through BAL, coinfection may explain one-fifth of causes for SMPP. Bronchoscopy with BAL may increase the detection rate of pathogen and resolve pulmonary lesions in patients with multilobar consolidation. IMPACT: Flexible bronchoscopy with bronchoalveolar lavage is of great assistance in the timely detection of coinfection, sputum plug and inflammatory polyps in children with Mycoplasma pneumoniae pneumonia (MPP), and improves the recovery of lung damage in MPP patients with multilobar consolidation. This study provides new insights into the indications of flexible bronchoscopy for the diagnosis and treatment of pediatric patients with MPP.

Synergy effects of Methylomonas koyamae and Hyphomicrobium methylovorum under methanethiol stress.

Methanotrophs are able to metabolize volatile organic sulfur compounds (VOSCs), excrete organic carbon during CH4 oxidation, and influence microbial community structure and function of the ecosystem. In return, microbial community structure and environmental factors can affect the growth metabolism of methanotrophs. In this study, Methylomonas koyamae and Hyphomicrobium methylovorum were used for model organisms, and methanethiol (MT) was chosen for a typical VOSC to investigate the synergy effects under VOSC stress. The results showed that when Hyphomicrobium methylovorum was co-cultured with Methylomonas koyamae in the medium with CH4 used as the carbon source, the co-culture had better MT tolerance relative to Methylomonas koyamae and oxidized all CH4 within 120 h, even at the initial MT concentration of 2000 mg m-3. The optimal co-culture ratios of Methylomonas koyamae to Hyphomicrobium methylovorum were 4:1-12:1. Although MT could be converted spontaneously to dimethyl disulfide (DMDS), H2S, and CS2 in air, faster losses of MT, DMDS, H2S, and CS2 were observed in each strain mono-culture and the co-culture. Compared with Hyphomicrobium methylovorum, MT was degraded more quickly in the Methylomonas koyamae culture. During the co-culture, the CH4 oxidation process of Methylomonas koyamae could provide carbon and energy sources for the growth of Hyphomicrobium methylovorum, while Hyphomicrobium methylovorum oxidized MT to help Methylomonas koyamae detoxify. These findings are helpful to understand the synergy effects of Methylomonas koyamae and Hyphomicrobium methylovorum under MT stress and enrich the role of methanotrophs in the sulfur biogeochemical cycle. KEY POINTS: • The co-culture of Methylomonas and Hyphomicrobium has better tolerance to CH3SH. • Methylomonas can provide carbon sources for the growth of Hyphomicrobium. • The co-culture of Methylomonas and Hyphomicrobium enhances the removal of CH4 and CH3SH.

Predictive models for sepsis in children with Staphylococcus aureus bloodstream infections: a retrospective cohort study.

BACKGROUND: The presence of Staphylococcus aureus in the bloodstream can lead to the development of sepsis; however, the severity and risk factors of the systemic inflammatory response to Staphylococcus aureus bloodstream infections were unclear. This study is aimed to build a model to predict the risk of sepsis in children with Staphylococcus aureus bloodstream infections. METHODS: A retrospective analysis of hospitalized pediatric patients diagnosed with Staphylococcus aureus bloodstream infections was performed between January 2013 and December 2019. Each patient was assessed using the pediatric version of the Sequential Organ Failure Assessment score (pSOFA) within 24 h of blood culture collection. A nomogram based on logistic regression models was constructed to predict the risk factors for sepsis in children with Staphylococcus aureus bloodstream infections. It was validated using the area under the receiver-operating characteristic curve (AUC). RESULTS: Of the 94 patients included in the study, 35 cases (37.2%) developed sepsis. The pSOFA scores ranged from 0 to 8, with 35 patients having a pSOFA score of ≥ 2. Six children (6.4%) died within 30 days, who were all from the sepsis group and had different pSOFA scores. The most common organs involved in sepsis in children with staphylococcal bloodstream infections were the neurologic system (68.6%), respiratory system (48.6%), and coagulation system (45.7%). Hospital-acquired infections (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.3-7.2), implanted catheters (aOR, 10.4; 95% CI, 3.8-28.4), procalcitonin level ≥ 1.7 ng/mL (aOR, 15.4; 95% CI, 2.7-87.1), and underlying diseases, especially gastrointestinal malformations (aOR, 14.0; 95% CI, 2.9-66.7) were associated with Staphylococcus aureus sepsis. However, methicillin-resistant Staphylococcus aureus infection was not a risk factor for sepsis. The nomogram had high predictive accuracy for the estimation of sepsis risk, with an AUC of 0.85. CONCLUSIONS: We developed a predictive model for sepsis in children with Staphylococcus aureus infection.

Distributed Optical Measurement System for Plate Fin Heat Exchanger.

The acquirement of the flow information in plate-fin heat exchanger (PFHE) is limited by its metal structure and complex flow condition. This work develops a new distributed optical measurement system to obtain flow information and boiling intensity. The system utilizes numerous optical fibers installed at the surface of the PFHE to detect optical signals. The attenuation and fluctuation of the signals reflect the variation of the gas-liquid interfaces and can be further used to estimate the boiling intensity. Practical experiments of flow boiling in PFHE with different heating fluxes have been carried out. The results verify that the measurement system can obtain the flow condition. Meanwhile, according to the results, the boiling development in PFHE can be divided into four stages with the increase in the heating flux, including the unboiling stage, initiation stage, boiling developing stage, and fully developed stage.

Employee posts on personal social media: the mediation role of work-life conflict on employee engagement.

Personal social media, as a private space, seems to have become another important arena for employees to share work-related posts, and the number of employee posts on social media is proliferating. However, academic scrutiny of the impact of social media usage remains inconclusive, and little is known regarding how employee posts affect employee engagement. The present study aims to fill this crucial gap in the existing research by constructing a conceptual model to unravel how employee posts shared on different personal social media platforms (strong-tie vs. weak-tie) influence employee engagement, as well as the moderating role of post content and employees' work-life segmentation preferences. Taking the Chinese workplace as a case, we conducted a survey of 402 participants from more than 30 organizations. The results revealed that employee posts on strong-tie social media platforms will lower employee engagement via the mediating role of work-life conflict. Moreover, these negative effects can be attenuated for sharing user-oriented posts (vs. organization-oriented posts) and employees with lower segmentation preferences, confirming the moderating role of post content and segmentation preferences. The findings contribute to the theoretical understanding of employee engagement by expanding boundary theory, and provide managerial implications for social media strategies, and organizational support.

Red blood cell distribution width and tumor necrosis factor-α for the early prediction of coronary artery lesion in Kawasaki disease: a retrospective study.

We aimed to identify novel risk factors for the early prediction of coronary artery lesion (CAL) in children with Kawasaki disease (KD). We retrospectively analyzed data from hospitalized children newly diagnosed with KD between January 1, 2018, and December 31, 2020, with the following inclusion criteria: (1) diagnosis of KD, (2) first onset of CAL after admission, (3) with complete clinical records. Demographic and laboratory data were collected and analyzed. The independent risk factors of KD combined with CAL were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the efficacy of identified risk factors in predicting KD combined with CAL. Among 241 initially recruited patients, 226 were eligible to be included in the study. Based on echocardiographic indications of CAL, 104 patients (46%) were assigned to the CAL (KD-CAL) group and 122 (54%) patients were assigned to the non-CAL (KD-nCAL) group. The levels of red blood cell count, red blood cell distribution width (RDW), C-reactive protein, tumor necrosis factor-α (TNF-α), and interleukin-6 were significantly higher in the KD-CAL group than those in the KD-nCAL group (all p < 0.05). RDW and TNF-α were found as independent risk factors of CAL occurrence. The sensitivity and specificity of RDW, TNF-α, and RDW + TNF-α in predicting KD with CAL were 67.31% and 79.51%, 74.04% and 73.77%, and 79.81% and 80.33%, respectively.Conclusion: In conclusion, alterations in RDW and TNF-α levels can be used as novel biomarkers for early prediction of CAL in KD patients, although the differences in their absolute values were small and might not give any added value to echocardiography. What is Known: •Known risk factors of CAL in children with KD include male gender and delayed use of intravenous immune globulin. What is New: •Our current study identified that red blood cell distribution width (RDW) and tumor necrosis factor-α (TNF-α) are novel independent risk factors for predicting CAL combined with KD among patients. •The combination of these RDW and TNF-α together shows higher sensitivity and specificity than either one used alone.

Association of long-term effects of low-level sulfamethoxazole with ovarian lipid and amino acid metabolism, sex hormone levels, and oocyte maturity in zebrafish.

Sulfamethoxazole (SMZ) is an important antibiotic used to prevent and treat infections in both clinical settings and animal husbandry. High levels of SMZ may exhibit endocrine toxicity. Environmental SMZ enters the human body via food and water; however, the toxicity of environmental doses of SMZ and its effects on reproductive health are unknown. In the present study, zebrafish were exposed to low concentrations of SMZ (1000 and 5000 ng/L) from 2 h post-fertilization to 120 d post-fertilization. Consequently, the proportion of mature oocytes in adult female zebrafish ovarian tissue increased by 98.2 %, indicating that SMZ promotes ovarian maturation. Metabolomics analysis revealed significant changes in ovarian lipid and amino acid levels after SMZ treatment. An enzyme-linked immunoassay used to detect sex hormones in the ovaries showed that SMZ exposure significantly increased the levels of estradiol, a follicle-stimulating hormone, and of luteinizing hormone. Furthermore, an association analysis showed that most of the differentially expressed metabolites in the ovary were strongly correlated with the levels of sex hormones secreted by the pituitary gland. Therefore, significantly increased transcript levels of gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone detected in brain tissue suggested that SMZ may exhibit ovarian toxicity via the hypothalamus. In vitro experiments were performed to demonstrate that SMZ targets neurons in the hypothalamus. Exposure to SMZ significantly increased the GnRH content in GnRH neurons. Finally, molecular docking simulations indicated the potential interaction of SMZ with G protein-coupled receptor 54; this molecular binding can activate, synthesize, and release GnRH in neurons. In conclusion, long-term environmental exposure to SMZ may induce ovarian toxicity by affecting the hypothalamus-pituitary-gonad axis.

Long-term low-dose oxytetracycline potentially leads to neurobehavioural changes.

Trace levels of oxytetracycline (OTC)-a veterinary antibiotic and feed additive-are widespread in the environment. Studies revealed that OTC potentially impairs thyroid function, which may affect neurobehaviour; however, the impact of exposure to environmental concentrations of OTC on adult neurobehaviour is unknown. In this study, the effects of OTC on zebrafish after 30-day exposure were investigated. The total swimming distance was significantly increased under vibration and light/dark stimulation, while time spent in the white area was prolonged during the black/white preference test, indicating that the zebrafish became bolder and more impulsive under low OTC exposure. Additionally, monoamine neurotransmitter (5-hydroxytryptamine, dopamine, norepinephrine) levels were decreased and gene expression of monoamine oxidase (mao) involved in neurotransmitter metabolism was upregulated at the transcription level after OTC exposure. Because triiodothyronine (T3) levels were enhanced following exposure to OTC, we speculated that T3 may mediate OTC damage to the nervous system. Our simulated molecular docking analysis showed that OTC combined with the sodium iodide cotransporter protein may result in excessive T3 synthesis. We further exposed zebrafish to T3, and they exhibited similar behaviour to the OTC exposure group. In conclusion, environmental OTC may activate monoamine oxidase and enhance the metabolism of monoaminergic neurotransmitters via T3, thereby inducing abnormal neurobehaviour.

Ultralight Electrolyte for High-Energy Lithium-Sulfur Pouch Cells.

The high weight fraction of the electrolyte in lithium-sulfur (Li-S) full cell is the primary reason its specific energy is much below expectations. Thus far, it is still a challenge to reduce the electrolyte volume of Li-S batteries owing to their high cathode porosity and electrolyte depletion from the Li metal anode. Herein, we propose an ultralight electrolyte (0.83 g mL-1 ) by introducing a weakly-coordinating and Li-compatible monoether, which greatly reduces the weight fraction of electrolyte within the whole cell and also enables Li-S pouch cell functionality under lean-electrolyte conditions. Compared to Li-S batteries using conventional counterparts (≈1.2 g mL-1 ), the Li-S pouch cells equipped with our ultralight electrolyte could achieve an ultralow electrolyte weight/capacity ratio (E/C) of 2.2 g Ah-1 and realize a 19.2 % improvement in specific energy (from 329.9 to 393.4 Wh kg-1 ) under E/S=3.0 µL mg-1 . Moreover, more than 20 % improvement in specific energy could be achieved using our ultralight electrolyte at various E/S ratios.

A quantitative proteomics analysis for small molecule Stemazole's effect on human neural stem cells.

BACKGROUND: Stemazole is a novel small molecule that has been suggested to have the ability to protect multiple stem cells. The proliferation-promoting activity and promising neuroprotective effects of stemazole make it a prospective drug for neurodegenerative disease treatment. METHODS: Since previous studies have shown that it protective effect in extreme conditions, to understand more aspects of stemazole, in this study, a systematic tandem mass tags (TMT)-labelled proteomics approach was used to address the whole proteome expression profile with or without stemazole in normal conditions instead of extreme conditions. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction (PPI) network analyses, were employed. RESULTS: The effect of stemazole on the expression profiles of neural stem cells was obtained. A total of 408 proteins with changes at the abundance level of two groups were identified: 178 proteins increase in abundance and 240 proteins decrease in abundance, respectively. Low abundance of some mitochondrial respiratory chain enzyme, overproduction of reactive oxygen species (ROS) and reduction of mitochondrial membrane potential may indicate stemazole has cytotoxicity. CONCLUSIONS: It is the first proteomics research about stemazole, and the possible cytotoxicity of stemazole has been reported for the first time. The information about proteins that were affected by stemazole and more characteristics of stemazole will help obtain a complete picture of this small molecule drug. These findings provide a scientific basis for further stemazole treatment research.

Neonatal hand, foot, and mouth disease due to coxsackievirus A6 in Shanghai.

BACKGROUND: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. METHODS: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1ß, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings. RESULTS: There were 16 neonates among the 12,608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about 1 week after onset. None of the neonates had sequelae. CONCLUSIONS: In our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

Left ventricular remodeling and dysfunction in obstructive sleep apnea : Systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular mortality and morbidity. Several studies have reported that it affects the left ventricle; however, large randomized controlled trials are lacking. The current study aimed to summarize the association between OSAS and left ventricular (LV) structure and function. METHODS: Electronic databases (PubMed, Embase, and Cochrane) and references were searched for articles published until March 2018. A systematic review and meta-analysis were performed to assess LV structure and function in OSAS patients based on echocardiography. RESULTS: In total, 17 studies with 747 OSAS patients and 426 control participants were included. Patients with OSAS showed an increase in LV diastolic diameter (weighted mean difference [WMD], 95% CI: 1.24 [0.68, 1.80]; p < 0.001), LV systolic diameter (WMD, 95% CI: 1.14 [0.47, 1.81]; p = 0.001), and LV mass (WMD, 95% CI: 35.34 [20.67, 50.00]; p < 0.001). In addition, left ventricular ejection fraction (LVEF) significantly decreased in the OSAS group compared with the controls (WMD, 95% CIs: -1.82 [-2.76, -0.87]; p < 0.001), and the reduction in LVEF was consistent with the severity of OSAS. The OSAS group also showed an increase in left atrial diameter (WMD, 95% CI: 2.13 [1.48, 2.77]; p < 0.001) and left atrial diameter volume index (WMD, 95% CIs: 3.96 [3.32, 4.61]; p < 0.001). CONCLUSION: Obstructive sleep apnea syndrome leads to atrial dilatation, left ventricular hypertrophy, enlargement, mass increase and reduction of systolic function. Treatments for OSAS might be beneficial for the preservation of left cardiac structure and function.

Uncovering the Pharmacological Mechanism of Stemazole in the Treatment of Neurodegenerative Diseases Based on a Network Pharmacology Approach.

Stemazole exerts potent pharmacological effects against neurodegenerative diseases and protective effects in stem cells. However, on the basis of the current understanding, the molecular mechanisms underlying the effects of stemazole in the treatment of Alzheimer's disease and Parkinson's disease have not been fully elucidated. In this study, a network pharmacology-based strategy integrating target prediction, network construction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and molecular docking was adopted to predict the targets of stemazole relevant to the treatment of neurodegenerative diseases and to further explore the involved pharmacological mechanisms. The majority of the predicted targets were highly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. RAC-alpha serine/threonine-protein kinase (AKT1), caspase-3 (CASP3), caspase-8 (CASP8), mitogen-activated protein kinase 8 (MAPK8), and mitogen-activated protein kinase 14 (MAPK14) are the core targets regulated by stemazole and play a central role in its anti-apoptosis effects. This work provides a scientific basis for further elucidating the mechanism underlying the effects of stemazole in the treatment of neurodegenerative diseases.