A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription.

Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA-modifying enzyme provides a new perspective for understanding epitranscriptomic regulation.

2D Materials Kill Bacteria from Within.

Early work demonstrated that some two-dimensional (2D) materials could kill bacteria by using their sharp edges to physically rupture the bacteria envelope, which presents distinct advantages over traditional antibiotics, as bacteria are not able to evolve resistance to the former. This mechano-bactericidal mode of action, however, suffers from low antibacterial efficiency, fundamentally because of random orientation of 2D materials outside the bacteria, where the desirable "edge-to-envelope" contacts occur with low probability. Here, we demonstrate a proof-of-concept approach to significantly enhance the potency of the mechano-bactericidal activity of 2D materials. This approach is in marked contrast with previous work, as the 2D materials are designed to be in situ generated inside the bacteria from a molecularly engineered monomer in a self-assembled manner, profoundly promoting the probability of the "edge-to-envelope" contacts. The rationale in this study sheds light on a mechanically new nanostructure-enabled antibacterial strategy to combat antibiotic resistance.

Loss of threonyl-tRNA synthetase-like protein Tarsl2 has little impact on protein synthesis but affects mouse development.

Aminoacyl-tRNA synthetases (aaRSs) are essential components for mRNA translation. Two sets of aaRSs are required for cytoplasmic and mitochondrial translation in vertebrates. Interestingly, TARSL2 is a recently evolved duplicated gene of TARS1 (encoding cytoplasmic threonyl-tRNA synthetase) and represents the only duplicated aaRS gene in vertebrates. Although TARSL2 retains the canonical aminoacylation and editing activities in vitro, whether it is a true tRNA synthetase for mRNA translation in vivo is unclear. In this study, we showed that Tars1 is an essential gene since homozygous Tars1 KO mice were lethal. In contrast, when Tarsl2 was deleted in mice and zebrafish, neither the abundance nor the charging levels of tRNAThrs were changed, indicating that cells relied on Tars1 but not on Tarsl2 for mRNA translation. Furthermore, Tarsl2 deletion did not influence the integrity of the multiple tRNA synthetase complex, suggesting that Tarsl2 is a peripheral member of the multiple tRNA synthetase complex. Finally, we observed that Tarsl2-deleted mice exhibited severe developmental retardation, elevated metabolic capacity, and abnormal bone and muscle development after 3 weeks. Collectively, these data suggest that, despite its intrinsic activity, loss of Tarsl2 has little influence on protein synthesis but does affect mouse development.

Magnetic/Acoustic Dual-Controlled Microrobot Overcoming Oto-Biological Barrier for On-Demand Multidrug Delivery against Hearing Loss.

Multidrug combination therapy in the inner ear faces diverse challenges due to the distinct physicochemical properties of drugs and the difficulties of overcoming the oto-biologic barrier. Although nanomedicine platforms offer potential solutions to multidrug delivery, the access of drugs to the inner ear remains limited. Micro/nanomachines, capable of delivering cargo actively, are promising tools for overcoming bio-barriers. Herein, a novel microrobot-based strategy to penetrate the round window membrane (RWM) is presented and multidrug in on-demand manner is delivered. The tube-type microrobot (TTMR) is constructed using the template-assisted layer-by-layer (LbL) assembly of chitosan/ferroferric oxide/silicon dioxide (CS/Fe3O4/SiO2) and loaded with anti-ototoxic drugs (curcumin, CUR and tanshinone IIA, TSA) and perfluorohexane (PFH). Fe3O4 provides magnetic actuation, while PFH ensures acoustic propulsion. Upon ultrasound stimulation, the vaporization of PFH enables a microshotgun-like behavior, propelling the drugs through barriers and driving them into the inner ear. Notably, the proportion of drugs entering the inner ear can be precisely controlled by varying the feeding ratios. Furthermore, in vivo studies demonstrate that the drug-loaded microrobot exhibits superior protective effects and excellent biosafety toward cisplatin (CDDP)-induced hearing loss. Overall, the microrobot-based strategy provides a promising direction for on-demand multidrug delivery for ear diseases.

Boosting Polysulfide Redox Kinetics by Temperature-Induced Metal-Insulator Transition Effect of Tungsten-Doped Vanadium Dioxide for High-Temperature Lithium-Sulfur Batteries.

The practical application of Li-S batteries is still severely restricted by poor cyclic performance caused by the intrinsic polysulfides shuttle effect, which is even more severe under the high-temperature condition owing to the inevitable increase of polysulfides' solubility and diffusion rate. Herein, tungsten-doped vanadium dioxide (W-VO2) micro-flowers are employed with first-order metal-insulator phase transition (MIT) property as a robust and multifunctional modification layer to hamper the shuttle effect and simultaneously improve the thermotolerance of the common separator. Tungsten doping significantly reduces the transition temperature from 68 to 35 °C of vanadium dioxide, which renders the W-VO2 easier to turn from the insulating monoclinic phase into the metallic rutile phase. The systematic experiments and theoretical analysis demonstrate that the temperature-induced in-suit MIT property endows the W-VO2 catalyst with strong chemisorption against polysulfides, low energy barrier for liquid-to-solid conversion, and outstanding diffusion kinetics of Li-ion under high temperatures. Benefiting from these advantages, the Li-S batteries with W-VO2 modified separator exhibit significantly improved rate and long-term cyclic performance under 50 °C. Remarkably, even at an elevated temperature (80 °C), they still exhibit superior electrochemical performance. This work opens a rewarding avenue to use phase-changing materials for high-temperature Li-S batteries.

Large-scale identification of novel transcriptional regulators of the aliphatic glucosinolate pathway in Arabidopsis.

Aliphatic glucosinolates are a large group of plant secondary metabolites characteristic of Brassicaceae, including the model plant Arabidopsis. The diverse and complex degradation products of aliphatic glucosinolates contribute to plant responses to herbivory, pathogen attack, and environmental stresses. Most of the biosynthesis genes in the aliphatic glucosinolate pathway have been cloned in Arabidopsis, and the research focus has recently shifted to the regulatory mechanisms controlling aliphatic glucosinolate accumulation. Up till now, more than 40 transcriptional regulators have been identified as regulating the aliphatic glucosinolate pathway, but many more novel regulators likely remain to be discovered based on research evidence over the past decade. In the current study, we took a systemic approach to functionally test 155 candidate transcription factors in Arabidopsis identified by yeast one-hybrid assay, and successfully validated at least 30 novel regulators that could significantly influence the accumulation of aliphatic glucosinolates in our experimental set-up. We also showed that the regulators of the aliphatic glucosinolate pathway have balanced positive and negative effects, and glucosinolate metabolism and plant development can be coordinated. Our work is the largest scale effort so far to validate transcriptional regulators of a plant secondary metabolism pathway, and provides new insights into how the highly diverse plant secondary metabolism is regulated at the transcriptional level.

Reliability and validity of the Chinese revised version of the pectus excavatum evaluation questionnaire in children with pectus excavatum.

OBJECTIVE: This study aims to translate the Pectus Excavatum Evaluation Questionnaire(PEEQ) into Chinese, and to comprehensively assess subjective outcomes in quality of life of children with pectus excavatum. METHODS: The PEEQ was translated from English to Chinese as according to the PRO translation guidelines. Structural validity and reliability of the questionnaire were examined by validated factor analysis and Cronbach's alpha coefficient analysis respectively. RESULTS: The results of the validation factor analysis for the Chinese PEEQ parent's and child's questionnaires demonstrated that the fit indicators for each dimension met the required criteria. The overall Cronbach's alpha coefficient of parent's and child's questionnaires were 0.840 and 0.854. Both the item-level content validity index (I-CVI) and scale-level content validity index (S-CVI) of each sub-questionnaire were 1. CONCLUSION: The Chinese version of the PEEQ parent's questionnaire is suitable as a proxy assessment for patients with PE, but the child's questionnaire needs further adjustments.

Nasofacial Groove Pedicled Flap for the Reconstruction of Lateral Alar Defect.

BACKGROUND: The repair of nasal alar defects is challenging for plastic surgeons, and there is currently no standard operation. Herein, the authors reported the clinical outcomes of a nasofacial groove pedicled flap for the reconstruction of alar defect. METHODS: This retrospective study included patients who underwent the nasofacial groove pedicled flap for the reconstruction of alar defect between January 2018 and June 2020. Photographs of standard facial postures were taken before and after surgery to record the surgical results of the patients. The patient's medical history was reviewed retrospectively. Self-reported satisfaction of patients on scar morphology and reconstructive effect were evaluated with a questionnaire survey. RESULTS: There were 26 eligible patients enrolled, and all patients were followed up for more than 1 year after surgery. All flaps were free of ischemia and necrosis and healed well. No patient experienced restricted nostril ventilation. Eight patients underwent reoperation to trim the flap pedicle and the scar. Eight patients (8/26) reported "very satisfied," and 17 patients (17/26) reported "satisfied" with the repair effect and scar morphology. One patient went through multiple laser treatments to improve her scars but still remained visible hyperpigmentation. She was dissatisfied with postoperative flap pigmentation but was satisfied with the correction effect. CONCLUSIONS: The clinical results indicated that the nasal groove flap was safe for the treatment of the lateral alar defect, and the patients were satisfied with the clinical results. The authors believe that this flap can be used as an alternative method for repairing the lateral alar defect. LEVEL OF EVIDENCE: Level -IV, therapeutic study.

Human C15orf39 Inhibits Inflammatory Response via PRMT2 in Human Microglial HMC3 Cell Line.

Microglia-mediated inflammatory response is one key cause of many central nervous system diseases, like Alzheimer's disease. We hypothesized that a novel C15orf39 (MAPK1 substrate) plays a critical role in the microglial inflammatory response. To confirm this hypothesis, we used lipopolysaccharide (LPS)-and interferon-gamma (IFN-γ)-induced human microglia HMC3 cells as a representative indicator of the microglial in vitro inflammatory response. We found that C15orf39 was down-regulated when interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) expression increased in LPS/IFN-γ-stimulated HMC3 cells. Once C15orf39 was overexpressed, IL-6 and TNFα expression were reduced in LPS/IFN-γ-stimulated HMC3 cells. In contrast, C15orf39 knockdown promoted IL-6 and TNFα expression in LPS/IFN-γ-stimulated HMC3 cells. These results suggest that C15orf39 is a suppressive factor in the microglial inflammatory response. Mechanistically, C15orf39 interacts with the cytoplasmic protein arginine methyltransferase 2 (PRMT2). Thus, we termed C15orf39 a PRMT2 interaction protein (PRMT2 IP). Furthermore, the interaction of C15orf39 and PRMT2 suppressed the activation of NF-κB signaling via the PRMT2-IκBα signaling axis, which then led to a reduction in transcription of the inflammatory factors IL6 and TNF-α. Under inflammatory conditions, NF-κBp65 was found to be activated and to suppress C15orf39 promoter activation, after which it canceled the suppressive effect of the C15orf39-PRMT2-IκBα signaling axis on IL-6 and TNFα transcriptional expression. In conclusion, our findings demonstrate that in a steady condition, the interaction of C15orf39 and PRMT2 stabilizes IκBα to inhibit IL-6 and TNFα expression by suppressing NF-κB signaling, which reversely suppresses C15orf39 transcription to enhance IL-6 and TNFα expression in the microglial inflammatory condition. Our study provides a clue as to the role of C15orf39 in microglia-mediated inflammation, suggesting the potential therapeutic efficacy of C15orf39 in some central nervous system diseases.

Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus.

Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout (Fam210b-/-) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b-/- mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71+ erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71+ erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71+ erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.

The RNA-Binding Protein BoRHON1 Positively Regulates the Accumulation of Aliphatic Glucosinolates in Cabbage.

Aliphatic glucosinolates are an abundant group of plant secondary metabolites in Brassica vegetables, with some of their degradation products demonstrating significant anti-cancer effects. The transcription factors MYB28 and MYB29 play key roles in the transcriptional regulation of aliphatic glucosinolates biosynthesis, but little is known about whether BoMYB28 and BoMYB29 are also modulated by upstream regulators or how, nor their gene regulatory networks. In this study, we first explored the hierarchical transcriptional regulatory networks of MYB28 and MYB29 in a model plant, then systemically screened the regulators of the three BoMYB28 homologs in cabbage using a yeast one-hybrid. Furthermore, we selected a novel RNA binding protein, BoRHON1, to functionally validate its roles in modulating aliphatic glucosinolates biosynthesis. Importantly, BoRHON1 induced the accumulation of all detectable aliphatic and indolic glucosinolates, and the net photosynthetic rates of BoRHON1 overexpression lines were significantly increased. Interestingly, the growth and biomass of these overexpression lines of BoRHON1 remained the same as those of the control plants. BoRHON1 was shown to be a novel, potent, positive regulator of glucosinolates biosynthesis, as well as a novel regulator of normal plant growth and development, while significantly increasing plants' defense costs.

Biochemical component analysis of human myopic corneal stroma using the Raman spectrum.

PURPOSE: This study aimed to measure the Raman spectrum of the human corneal stroma lens obtained from small incision lenticule extraction surgery (SMILE) in Asian myopic eyes using a confocal Raman micro-spectrometer built in the laboratory. METHODS: Forty-three myopic patients who underwent SMILE with equivalent diopters between - 4.00 and - 6.00 D were selected, and the right eye data were collected. Corneal stroma lenses were obtained during surgery, and the Raman spectra were measured after air drying. The complete Raman spectrum of human myopic corneal stroma lens tissue was obtained within the range of 700-4000 cm-1. RESULTS: Thirteen characteristic peaks were found, with the stronger peaks appearing at 937 cm-1, corresponding to proline, valine, and the protein skeleton of the human myopic corneal stroma lens; 1243 cm-1, corresponding to collagen protein; 1448 cm-1, corresponding to the collagen protein and phospholipids; and 2940 cm-1, corresponding to the amino acid and lipids, which was the strongest Raman peak. CONCLUSION: These results demonstrated that Raman spectroscopy has much potential as a fast, cost-effective, and reliable diagnostic tool in the diagnosis and treatment of eye diseases, including myopia, keratoconus, and corneal infection.

Synthesis and Interlayer Assembly of a Graphenic Bowl with Peripheral Selenium Annulation.

Pentagonal cyclization at the bay positions of armchair-edged graphenic cores can build molecular bowls without the destruction of hexagonal lattices. However, this synthesis remains challenging due to unfavorable strain and the multiple reactions required. Here, we show that a new type of graphenic molecular bowl with a depth of 1.7 Å and a diameter of 1.2 nm is constructed by sextuple Se annulation at the bay positions of armchair-edged hexa-peri-hexabenzocoronene. This graphenic bowl is functionalized with phenylseleno groups that stack into a discrete bilayer dimer in solution. Such a dimer exhibits high stability and survives in the gas phase after laser ablation. Strikingly, the asymmetric one-dimensional supramolecular columns of graphenic bowl with coherent stacking configuration are observed in the solid state, which results in a strong second harmonic generation with prominent polarization dependence. Our findings present a concise synthesis of a giant molecular bowl with a graphenic core and demonstrate the unique supramolecular assembly of extended graphenic bowls.

Hexa-Branched Nanographenes with Large Two-Photon Absorption.

The conventional approach toward molecules with large two-photon absorption (TPA) involves donor-acceptor conjugation. Herein we show a new strategy involving the use of hexa-branched nanographenes. We synthesized two hexa-branched nanographenes, one with six benzoaceanthrylene arms fused to the coronene core and the other with six pyrenyl arms fused to the coronene core. Neither of these hexa-branched nanographenes has a donor-acceptor structure, yet they exhibited high TPA values of 3.6 × 103 and 1.9 × 104 GM, respectively, which are the highest values recorded for heteroatom-free hydrocarbon molecules. Theoretical analysis suggests that the fused branched structures are responsible for the large TPA cross-section. These findings illustrate the importance of the topology of the fused conjugated skeleton in TPA and provide an alternative structural design toward large TPA.

Target delivery of a PD-1-TREM2 scFv by CAR-T cells enhances anti-tumor efficacy in colorectal cancer.

BACKGROUND: Chimeric antigen receptor (CAR) -T cell therapy is an efficient therapeutic strategy for specific hematologic malignancies. However, positive outcomes of this novel therapy in treating solid tumors are curtailed by the immunosuppressive tumor microenvironment (TME), wherein signaling of the checkpoint programmed death-1 (PD-1)/PD-L1 directly inhibits T-cell responses. Although checkpoint-targeted immunotherapy succeeds in increasing the number of T cells produced to control tumor growth, the desired effect is mitigated by the action of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in the TME. Previous studies have confirmed that targeting triggering-receptor-expressed on myeloid cells 2 (TREM2) on TAMs and MDSCs enhances the outcomes of anti-PD-1 immunotherapy. METHODS: We constructed carcinoembryonic antigen (CEA)-specific CAR-T cells for colorectal cancer (CRC)-specific antigens with an autocrine PD-1-TREM2 single-chain variable fragment (scFv) to target the PD-1/PD-L1 pathway, MDSCs and TAMs. RESULTS: We found that the PD-1-TREM2-targeting scFv inhibited the activation of the PD-1/PD-L1 pathway. In addition, these secreted scFvs blocked the binding of ligands to TREM2 receptors present on MDSCs and TAMs, reduced the proportion of MDSCs and TAMs, and enhanced T-cell effector function, thereby mitigating immune resistance in the TME. PD-1-TREM2 scFv-secreting CAR-T cells resulted in highly effective elimination of tumors compared to that achieved with PD-1 scFv-secreting CAR-T therapy in a subcutaneous CRC mouse model. Moreover, the PD-1-TREM2 scFv secreted by CAR-T cells remained localized within tumors and exhibited an extended half-life. CONCLUSIONS: Together, these results indicate that PD-1-TREM2 scFv-secreting CAR-T cells have strong potential as an effective therapy for CRC.

Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: a cross-sectional study.

BACKGROUND: Despite the substantial burden caused by childhood cancer globally, childhood cancer incidence obtained in a nationwide childhood cancer registry and the accessibility of relevant health services are still unknown in China. We comprehensively assessed the most up-to-date cancer incidence in Chinese children and adolescents, nationally, regionally, and in specific population subgroups, and also examined the association between cancer incidence and socioeconomic inequality in access to health services. METHODS: In this national cross-sectional study, we used data from the National Center for Pediatric Cancer Surveillance, the nationwide Hospital Quality Monitoring System, and public databases to cover 31 provinces, autonomous regions, and municipalities in mainland China. We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China through stratified proportional estimation. We classified regions by socioeconomic status using the human development index (HDI). Incidence rates of 12 main groups, 47 subgroups, and 81 subtypes of cancer were reported and compared by sex, age, and socioeconomic status, according to the third edition of the International Classification of Childhood Cancer. We also quantified the geographical and population density of paediatric oncologists, pathology workforce, diagnoses and treatment institutions of paediatric cancer, and paediatric beds. We used the Gini coefficient to assess equality in access to these four health service indicators. We also calculated the proportions of cross-regional patients among new cases in our surveillance system. FINDINGS: We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China from Jan 1, 2018, to Dec 31, 2020. An estimated 121 145 cancer cases were diagnosed among children and adolescents in China between 2018 and 2020, with world standard age-standardised incidence rates of 122·86 (95% CI 121·70-124·02) per million for children and 137·64 (136·08-139·20) per million for adolescents. Boys had a higher incidence rate of childhood cancer (133·18 for boys vs 111·21 for girls per million) but a lower incidence of adolescent cancer (133·92 for boys vs 141·79 for girls per million) than girls. Leukaemias (42·33 per million) were the most common cancer group in children, whereas malignant epithelial tumours and melanomas (30·39 per million) surpassed leukaemias (30·08 per million) in adolescents as the cancer with the highest incidence. The overall incidence rates ranged from 101·60 (100·67-102·51) per million in very low HDI regions to 138·21 (137·14-139·29) per million in high HDI regions, indicating a significant positive association between the incidence of childhood and adolescent cancer and regional socioeconomic status (p<0·0001). The incidence in girls showed larger variation (48·45% from the lowest to the highest) than boys (36·71% from lowest to highest) in different socioeconomic regions. The population and geographical densities of most health services also showed a significant positive correlation with HDI levels. In particular, the geographical density distribution (Gini coefficients of 0·32-0·47) had higher inequalities than population density distribution (Gini coefficients of 0·05-0·19). The overall proportion of cross-regional patients of childhood and adolescent cancer was 22·16%, and the highest proportion occurred in retinoblastoma (56·54%) and in low HDI regions (35·14%). INTERPRETATION: Our study showed that the burden of cancer in children and adolescents in China is much higher than previously nationally reported from 2000 to 2015. The distribution of the accessibility of health services, as a social determinant of health, might have a notable role in the socioeconomic inequalities in cancer incidence among Chinese children and adolescents. With regards to achieving the Sustainable Development Goals, policy approaches should prioritise increasing the accessibility of health services for early diagnosis to improve outcomes and subsequently reduce disease burdens, as well as narrowing the socioeconomic inequalities of childhood and adolescent cancer. FUNDING: National Major Science and Technology Projects of China, National Natural Science Foundation of China, Chinese Academy of Engineering Consulting Research Project, Wu Jieping Medical Foundation, Beijing Municipal Administration of Hospitals Incubating Program.

Modulating d-Band Electronic Structures of Molybdenum Disulfide via p/n Doping to Boost Polysulfide Conversion in Lithium-Sulfur Batteries.

Polysulfide shuttle effect and sluggish sulfur reaction kinetics severely impede the cycling stability and sulfur utilization of lithium-sulfur (Li-S) batteries. Modulating d-band electronic structures of molybdenum disulfide electrocatalysts via p/n doping is promising to boost polysulfide conversion and suppress polysulfide migration in lithium-sulfur batteries. Herein, p-type V-doped MoS2 (V-MoS2 ) and n-type Mn-doped MoS2 (Mn-MoS2 ) catalysts are well-designed. Experimental results and theoretical analyses reveal that both of them significantly increase the binding energy of polysulfides on the catalysts' surface and accelerate the sluggish conversion kinetics of sulfur species. Particularly, the p-type V-MoS2 catalyst exhibits a more obvious bidirectional catalytic effect. Electronic structure analysis further demonstrates that the superior anchoring and electrocatalytic activities are originated from the upward shift of the d-band center and the optimized electronic structure induced by duplex metal coupling. As a result, the Li-S batteries with V-MoS2 modified separator exhibit a high initial capacity of 1607.2 mAh g-1 at 0.2 C and excellent rate and cycling performance. Moreover, even at a high sulfur loading of 6.84 mg cm-2 , a favorable initial areal capacity of 8.98 mAh cm-2 is achieved at 0.1 C. This work may bring widespread attention to atomic engineering in catalyst design for high-performance Li-S batteries.

Detecting genomic mosaicism in "de novo" genetic epilepsy by amplicon-based deep sequencing.

AIM: To investigate the occurrence of mosaicism in epilepsy probands and their parents using amplicon-based deep sequencing (ADS). METHODS: Patients were recruited from the outpatient of Peking University First Hospital. Two hundred and sixty-four probands with pathogenic variants tested by next-generation sequencing (NGS) were enrolled. RESULTS: Mosaic variants were detected in seventeen disease-associated genes from 20 probands, 5 paternal, and 6 maternal parents. The frequency of mosaicism was 11.74% (31/264). Mosaicism in 11 genes was identified from 20 probands with the mutant allelic fractions (MAFs) of 12.95-38.00% in autosomal dominant genes. Five paternal mosaicisms were identified in genes with a MAF of 6.30-20.99%, and six maternal mosaic individuals with a MAF of 2.07-21.90%. Only four mosaic parents had milder seizure history. The affected sibling had the same phenotype consistent with that of the proband, who inherited the variant of SLC1A2 or STXBP1 from their unaffected mosaic mothers, respectively. INTERPRETATION: Mosaic phenomenon is not rare in families with epilepsy. Phenotypes of mosaic parents were milder or normal. Mosaicism detection is helpful to identify the mutation origin and it provides a theoretical basis for prenatal diagnosis of family reproduction. ADS is a reliable way of mosaicism detection for clinical application.

Mendelian randomization study on the causal effect of chickenpox on dementia.

Some viruses, such as varicella zoster virus, are associated with severe dementia. The present study aims to identify the causal link between chickenpox and dementia. To date, the largest publicly available genome-wide association study (GWAS) for chickenpox (710 cases and 211 856 controls from European individuals) and for dementia (5933 cases and 212 859 controls from European individuals) were used to performed this two-sample Mendelian randomization (MR) study. We found no significant pleiotropy or heterogeneity in all seven selected chickenpox genetic instrumental variants in dementia GWAS. Of seven chickenpox genetic variants, two are located in the intergenic region and five are located in intron. We found that as chickenpox genetically increased, dementia risk increased based on an inverse-variance weighted analysis (ß = 0.070, 95% confidence interval [CI] for ß: 0.014-0.126; odds ratio [OR] = 1.073, 95% CI for OR: 1.015-1.134; p = 0.014) and weighted median (ß = 0.071, 95% CI for ß: 0.002-0.141; OR = 1.074, 95% CI for OR: 1.002-1.152; p = 0.045). Reverse MR analysis showed no causal effect of dementia on chickenpox. Our analysis suggests a causal effect of genetically increased chickenpox on dementia risk. Thus, chickenpox may be a potential risk factor for dementia.

Chickenpox and multiple sclerosis: A Mendelian randomization study.

Observational studies have suggested a suspected association between varicella-zoster virus (VZV) infection and multiple sclerosis (MS), but the connection has remained unclear. The aim of the present study is to evaluate the causal relationship between chickenpox which is caused by VZV infection and MS. We performed a two-sample Mendelian randomization analysis to investigate the association of chickenpox with MS using summary statistics from genome-wide association studies (GWAS). The GWAS summary statistics data for chickenpox was from the 23andMe cohort including 107 769 cases and 15 982 controls. A large summary of statistical data from the International Multiple Sclerosis Genetics Consortium (IMSGC) was used as the outcome GWAS data set, including 14 802 MS cases and 26 703 controls. We found evidence of a significant association between genetically predicted chickenpox and risk of MS (odds ratio [OR] = 35.27, 95% confidence interval [CI] = 22.97-54.17, p = 1.46E-59). Our findings provided evidence indicating a causal effect of chickenpox on MS. Further elucidations of this association and underlying mechanisms are needed for identifying feasible interventions to promote MS prevention.