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Rational architecture design of the artificial protective layer on the zinc (Zn) anode surface is a promising strategy to achieve uniform Zn deposition and inhibit the uncontrolled growth of Zn dendrites. Herein, a red phosphorous-derived artificial protective layer combined with a conductive N-doped carbon framework is designed to achieve dendrite-free Zn deposition. The Zn-phosphorus (ZnP) solid solution alloy artificial protective layer is formed during Zn plating. Meanwhile, the dynamic evolution mechanism of the ZnP on the Zn anode is successfully revealed. The concentration gradient of the electrolyte on the electrode surface can be redistributed by this protective layer, thereby achieving a uniform Zn-ion flux. The fabricated Zn symmetrical battery delivers a dendrite-free plating/stripping for 1100 h at the current density of 2.0 mA cm -2 . Furthermore, aqueous Zn//MnO 2 full cell exhibits a reversible capacity of 200 mAh g -1 after 350 cycles at 1.0 A g -1 . This study suggests an effective solution for the suppression of Zn dendrites in Zn metal batteries, which is expected to provide a deep insight into the design of high-performance rechargeable aqueous Zn-ion batteries., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: While online orthopedic resources are becoming an increasingly popular avenue for patient education, videos on YouTube are not subject to peer review. The purpose of this cross-sectional study was to evaluate the quality of YouTube videos for patient education in ulnar collateral ligament (UCL) injuries of the elbow., Methods: A search of keywords for UCL injury was conducted through the YouTube search engine. Each video was categorized by source and content. Video quality, reliability, and accuracy were assessed by two independent raters using five metrics: (1) Journal of American Medical Association (JAMA) benchmark criteria (range 0-4) for video reliability; (2) modified DISCERN score (range 1-5) for video reliability; (3) Global Quality Score (GQS; range 1-5) for video quality; (4) ulnar collateral ligament-specific score (UCL-SS; range 0-16), a novel score for comprehensiveness of health information presented; and (5) accuracy score (AS; range 1-3) for accuracy., Results: Video content was comprised predominantly of disease-specific information (52%) and surgical technique (33%). The most common video sources were physician (42%) and commercial (23%). The mean JAMA score, modified DISCERN score, GQS, UCL-SS, and AS were 1.8, 2.4, 1.9, 5.3, and 2.7 respectively., Conclusions: Overall, YouTube is not a reliable or high-quality source for patients seeking information regarding UCL injuries, especially with videos uploaded by non-physician sources. The multiplicity of low quality, low reliability, and irrelevant videos can create a cumbersome and even inaccurate learning experience for patients.

Bacterial infections have become a severe threat to human health and antibiotics have been developed to treat them. However, extensive use of antibiotics has led to multidrug-resistant bacteria and reduction of their therapeutic effects. An efficient solution may be localized application of antibiotics using a drug delivery system. For clinical application, they need to be biodegradable and should offer a prolonged antibacterial effect. In this study, a new injectable and visible-light-crosslinked hyaluronic acid (HA) hydrogel loaded with silicon (Si)-based nickel oxide (NiO) nanoflowers (Si@NiO) as an antibacterial scaffold was developed. Si@NiO nanoflowers were synthesized using chemical bath deposition before encapsulating them in the HA hydrogel under a mild visible-light-crosslinking conditions to generate a Si@NiO-hydrogel. Si@NiO synthesis was confirmed using scanning electron microscopy, transmission electron microscopy, and powder X-ray diffraction. As-prepared Si@NiO-hydrogel exhibited enhanced mechanical properties compared to a control bare hydrogel sample. Moreover, Si@NiO-hydrogel exhibits excellent antibacterial properties against three bacterial strains (P. aeruginosa, K. pneumoniae, and methicillin-resistant Staphylococcus aureus (>99.9% bactericidal rate)) and negligible cytotoxicity toward mouse embryonic fibroblasts. Therefore, Si@NiO-hydrogel has the potential for use in tissue engineering and biomedical applications owing to its injectability, visible-light crosslink ability, degradability, biosafety, and superior antibacterial property., (Copyright © 2022. Published by Elsevier B.V.)

Oil-contaminated soil is a major societal problem for humans and the environment. In this study, the pyrolysis method was applied to oil-contaminated soil used as a landfill and gas station site in Korea. The removal efficiency of the main components of oil-contaminated soils, such as total petroleum hydrocarbons (TPH), polyaromatic hydrocarbons (PAHs), unresolved complex mixture (UCM), and alkylated PAHs (Alk-PAHs) were measured, and the effect of temperature, treatment time, and moisture content on pyrolysis efficiency was studied. In order to evaluate the risk of soil from which pollutants were removed through pyrolysis, integrated ecotoxicity was evaluated using Daphnia magna and Allivibrio fischeri . The chemical and biological measurements in this study include contaminants of emerging concerns (CECs). Results showed that the pyrolysis was more efficient with higher treatment temperatures, moisture content, and treatment times. In addition, toxicity was reduced by 99% after pyrolysis, and the degree of toxicity was evaluated more sensitively in Allivibrio fischeri than in Daphnia magna . This study shows that weathered oil-contaminated soil can be effectively treated in a relatively short time through pyrolysis, as well as provides information on efficient conditions and the assessment of ecotoxicity.

Ensartinib (X-396) is a promising second-generation small-molecule inhibitor of anaplastic lymphoma kinase (ALK) that was developed for the treatment of ALK-positive non-small-cell lung cancer. Preclinical and clinical trial results for ensartinib showed superior efficacy and a favorable safety profile compared to the first-generation ALK inhibitors that have been approved by the U.S. Food and Drug Administration. Although the potential mechanisms of acquired resistance to ensartinib have not been reported, the inevitable emergence of resistance to ensartinib may limit its therapeutic application in cancer. In this work, we investigated the interaction of ensartinib with P-glycoprotein (P-gp) and ABCG2, two ATP-binding cassette (ABC) multidrug efflux transporters that are commonly associated with the development of multidrug resistance in cancer cells. Our results revealed that P-gp overexpression, but not expression of ABCG2, was associated with reduced cancer cell susceptibility to ensartinib. P-gp directly decreased the intracellular accumulation of ensartinib, and consequently reduced apoptosis and cytotoxicity induced by this drug. The cytotoxicity of ensartinib could be significantly reversed by treatment with the P-gp inhibitor tariquidar. In conclusion, we report that ensartinib is a substrate of P-gp, and provide evidence that this transporter plays a role in the development of ensartinib resistance. Further investigation is needed.

Background: Withania somnifera (Solanaceae), generally known as Indian ginseng, is a medicinal plant that is used in Ayurvedic practice for promoting health and longevity. This study aims to identify the bioactive metabolites from Indian ginseng and elucidate their structures., Methods: Withanolides were purified by chromatographic techniques, including HPLC coupled with LC/MS. Chemical structures of isolated withanolides were clarified by analyzing the spectroscopic data from 1D and 2D NMR, and HR-ESIMS experiment. Absolute configurations of the withanolides were established by the application of NMR chemical shifts and ECD calculations. Anti-adipogenic activities of isolates were evaluated using 3T3-L1 preadipocytes with Oil Red O staining and quantitative real-time PCR (qPCR)., Results: Phytochemical examination of the roots of Indian ginseng afforded to the isolation of six withanolides ( 1 - 6 ), including three novel withanolides, withasilolides G-I ( 1 - 3 ). All the six compounds inhibited adipogenesis and suppressed the enlargement of lipid droplets, compared to those of the control. Additionally, the mRNA expression levels of Fabp4 and Adipsin , the adipocyte markers decreased noticeably following treatment with 25 μM of 1 - 6 . The active compounds ( 1 - 6 ) also promoted lipid metabolism by upregulating the expression of the lipolytic genes HSL and ATGL and downregulating the expression of the lipogenic gene SREBP1., Conclusion: The results of our experimental studies suggest that the withasilolides identified herein have anti-adipogenic potential and can be considered for the development of therapeutic strategies against adipogenesis in obesity. Our study also provides a mechanistic rationale for using Indian ginseng as a potential therapeutic agent against obesity and related metabolic diseases., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

In this study, the pharmacokinetic profiles of the bioactive components in the leaf extract of the medicinal herb, Cudrania tricuspidate, were investigated using an MS/MS-based molecular networking system. To identify the major active components of the C. tricuspidate leaf extract (CLE), HPLC-DAD analysis was conducted with a standard mixture of six flavonoids (rutin, isoquercitrin, nicotiflorin, kaempferol 3-O-glucoside, quercetin, and kaempferol). The unknown peaks were determined via molecular networking analysis using the mass dataset obtained by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). For the subsequent pharmacokinetic study, CLE (1 g/kg) was orally administered to rats, and plasma samples were collected. The product ion mass data of plasma samples using LC-QTOF/MS were obtained and subjected to molecular networking analysis. The resulting molecular networking map indicated that the glucuronide metabolites of quercetin and kaempferol were the major circulating species. Accordingly, quercetin and kaempferol were determined following β-glucuronidase treatment, and their pharmacokinetic parameters were calculated. These findings indicate that the proposed molecular network-based approaches are potential and efficient methods for the pharmacokinetic study of herbal medicines., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Shoulder arthroplasty is a common orthopedic procedure with a complication rate reported to be as high as 39.8% and revision rates as high as 11%. Symptoms related to postoperative difficulties include activity-related pain, decreased range of motion, and apprehension. Some patients report immediate and persistent dissatisfaction, although others report a symptom-free postoperative period followed by increasing pain and decreasing shoulder function and mobility. Imaging plays an important role in diagnosing postoperative complications of shoulder arthroplasties. The imaging algorithm should always begin with radiographs. The selection of the next imaging modality depends on several factors, including findings on the initial imaging study, clinical suspicion of an osseous versus soft-tissue injury, and clinical suspicion of infection.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Triboelectric nanogenerators (TENGs) are one of the most trending energy harvesting devices because of their efficient and simple mechanism in harvesting mechanical energy from the environment into electricity. Herein, ferroelectric and dielectric bismuth tungstate (Bi 2 WO 6 (BWO)) with a marigold flower-like structure is prepared via a hydrothermal method, which is embedded in poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP), forming a PVDF-HFP/BWO composite polymer film (CPF) to fabricate TENGs. Generally, the ferroelectric materials exhibit a large piezoelectric coefficient, high electrostatic dipole moment, and high dielectric constant. The prepared PVDF-HFP/BWO CPF reveals a high polar crystalline β-phase which leads to enhanced piezoelectric and ferroelectric properties of the CPF, thus resulting in the increased electrical performance of the fabricated TENG. The electrical output performance of the proposed TENG is systematically investigated by varying the amount of BWO material embedded in the PVDF-HFP polymer. The fabricated PVDF-HFP/2.5 wt% BWO CPF-based TENG device exhibits the highest electrical output performance. Additionally, the robust test of the TENG device is conducted to investigate the electrical performance for long-term durability and mechanical stability. Finally, the proposed TENG is operated as a self-powered sensor, harvesting mechanical energy from daily life human activities, and powering various low-power portable electronics., (© 2022 Wiley-VCH GmbH.)

The methylerythritol 4-phosphate (MEP) pathway is responsible for providing common precursors for the biosynthesis of diverse plastidial terpenoids, including chlorophylls, carotenoids, and phytohormones, in plants. In rice ( Oryza sativa ), the last-step genes encoding 4-hydroxy-3-methylbut-2-enyl diphosphate reductase [HDR/isoprenoid synthesis H (IspH)] have been annotated in two genes ( OsIspH1 and OsIspH2 ) in the rice genome. The spatial transcript levels indicated that OsIspH1 is highly expressed in all tissues at different developmental stages, whereas OsIspH2 is barely expressed due to an early stop in exon 1 caused by splicing error. OsIspH1 localized into plastids and osisph1 , a T-DNA inserted knockout mutant, showed an albino phenotype, indicating that OsIspH1 is the only functional gene. To elucidate the role of OsIspH1 in the MEP pathway, we created two single (H145P and K407R) and double (H145P/K407R) mutations and performed complementation tests in two hdr mutants, including Escherichia coli DLYT1 strains and osisph1 rice plants. The results showed that every single mutation retained HDR function, but a double mutation lost it, proposing that the complementary relations of two residues might be important for enzyme activity but not each residue. When overexpressed in rice plants, the double-mutated gene, OsIspH1 MUT , reduced chlorophyll and carotenoid biosynthesis in the leaves and seeds. It confirmed the crucial role of OsIspH1 in plastidic terpenoid biosynthesis, revealing organ-specific differential regulation of OsIspH1 in rice plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Kim, Baek, Yu, You and Ha.)

The singly Cabibbo-suppressed decay Λ_{c}^{+}→nπ^{+} is observed for the first time with a statistical significance of 7.3σ by using 3.9  fb^{-1} of e^{+}e^{-} collision data collected at center-of-mass energies between 4.612 and 4.699 GeV with the BESIII detector at BEPCII. The branching fraction of Λ_{c}^{+}→nπ^{+} is measured to be (6.6±1.2_{stat}±0.4_{syst})×10^{-4}. By taking the upper limit of branching fractions of Λ_{c}^{+}→pπ^{0} from the Belle experiment, the ratio of branching fractions between Λ_{c}^{+}→nπ^{+} and Λ_{c}^{+}→pπ^{0} is calculated to be larger than 7.2 at the 90% confidence level, which disagrees with most predictions of the available phenomenological models. In addition, the branching fractions of the Cabibbo-favored decays Λ_{c}^{+}→Λπ^{+} and Λ_{c}^{+}→Σ^{0}π^{+} are measured to be (1.31±0.08_{stat}±0.05_{syst})×10^{-2} and (1.22±0.08_{stat}±0.07_{syst})×10^{-2}, respectively, which are consistent with previous results.

Background: Oral cavity squamous cell carcinoma (OSCC) is an aggressive malignant tumor with high recurrence and poor prognosis in the advanced stage. Patient-derived xenografts (PDXs) serve as powerful preclinical platforms for drug testing and precision medicine for cancer therapy. We assess which molecular signatures affect tumor engraftment ability and tumor growth rate in OSCC PDXs., Methods: Treatment-naïve OSCC primary tumors were collected for PDX models establishment. Comprehensive genomic analysis, including whole-exome sequencing and RNA-seq, was performed on case-matched tumors and PDXs. Regulatory genes/pathways were analyzed to clarify which molecular signatures affect tumor engraftment ability and the tumor growth rate in OSCC PDXs., Results: Perineural invasion was found as an important pathological feature related to engraftment ability. Tumor microenvironment with enriched hypoxia, PI3K-Akt, and epithelial-mesenchymal transition pathways and decreased inflammatory responses had high engraftment ability and tumor growth rates in OSCC PDXs. High matrix metalloproteinase-1 (MMP1) expression was found that have a great graft advantage in xenografts and is associated with pooled disease-free survival in cancer patients., Conclusion: This study provides a panel with detailed genomic characteristics of OSCC PDXs, enabling preclinical studies on personalized therapy options for oral cancer. MMP1 could serve as a biomarker for predicting successful xenografts in OSCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yen, Chang, Chang, Ouyang, Liu, Tsai, Zhang, Wang, Wang, Yu, Liu, Wu, Chang, Yu and Yang.)

Background: Colorectal cancer (CRC) is a major health concern globally, but exhibits regional and/or environmental distinctions in terms of outcome especially for patients with stage III CRC., Methods: From 2014 to 2016, matched pairs of tumor and adjacent normal tissue samples from 60 patients with stage I-IV CRC from Chang Gung Memorial Hospital in Taiwan were analyzed using next-generation sequencing. The DNA, mRNA, and miRNA sequences of paired tumor tissues were profiled. An observational study with survival analysis was done. Online datasets of The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) were also integrated and compared., Results: The gene that exhibited the highest mutation rate was adenomatous polyposis coli (APC) (75.0%), followed by TP53 (70.0%), KRAS (56.6%), and TTN (48.3%). APC was also the most frequently mutated gene in TCGA and ICGC datasets. Surprisingly, for non-metastatic cases (stages I-III), CRC patients with mutated APC had better outcome in terms of overall survival (p = 0.041) and recurrence free survival (p = 0.0048). Particularly for stage III CRC, the overall survival rate was 94.4% and 67.7%, respectively (p = 0.018), and the recurrence free survival rate was 94.4% and 16.7%, respectively (p = 0.00044). Further clinical and gene expression analyses revealed that the APC wt specimens to a greater extent exhibit poor differentiation state as well as EGFR upregulation, providing molecular basis for the poor prognosis of these patients. Finally, based on integrated transcriptome analysis, we constructed the mRNA-miRNA networks underlying disease recurrence of the stage III CRC and uncovered potential therapeutic targets for this clinical condition., Conclusion: For stage III CRC, patients with mutated APC had better overall and recurrence free survival., Competing Interests: Conflicts of interest The authors disclose no potential conflicts of interest., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Covering: up to June 2021A wide variety of mushrooms have traditionally been recognized as edible fungi with high nutritional value and low calories, and abundantly produce structurally diverse and bioactive secondary metabolites. However, accidental ingestion of poisonous mushrooms can result in serious illnesses and even death. Chemically, mushroom poisoning is associated with secondary metabolites produced in poisonous mushrooms, causing specific toxicity. However, many poisonous mushrooms have not been fully investigated for their secondary metabolites, and the secondary metabolites of poisonous mushrooms have not been systematically summarized for details such as chemical composition and biosynthetic mechanisms. The isolation and identification of secondary metabolites from poisonous mushrooms have great research value since these compounds could be lethal toxins that contribute to the toxicity of mushrooms or could provide lead compounds with remarkable biological activities that can promote advances in other related disciplines, such as biochemistry and pharmacology. In this review, we summarize the structures and biological activities of secondary metabolites identified from poisonous mushrooms and provide an overview of the current information on these metabolites, focusing on their chemistry, bioactivity, and biosynthesis.

Withania somnifera (Solanaceae), commonly known as "ashwagandha", is an ayurvedic medicinal plant that has been used for promoting good health and longevity. As part of our ongoing natural product research for the discovery of bioactive phytochemicals with novel structures, we conducted a phytochemical analysis of W. somnifera root, commonly used as an herbal medicine part. The phytochemical investigation aided by liquid chromatography-mass spectrometry (LC/MS)-based analysis led to the isolation of four withanolide glycosides ( 1 - 4 ), including one new compound, withanoside XII ( 1 ), from the methanol (MeOH) extract of W. somnifera root. The structure of the new compound was determined by nuclear magnetic resonance (NMR) spectroscopic data, high-resolution (HR) electrospray ionization (ESI) mass spectroscopy (MS), and electronic circular dichroism (ECD) data as well as enzymatic hydrolysis followed by LC/MS analysis. In addition, enzymatic hydrolysis of 1 afforded an aglycone ( 1a ) of 1 , which was identified as a new compound, withanoside XIIa ( 1a ), by the interpretation of NMR spectroscopic data, HR-ESIMS, and ECD data. To the best of our knowledge, the structure of compound 2 (withagenin A diglucoside) was previously proposed by HRMS and MS/MS spectral data, without NMR experiment, and the physical and spectroscopic data of withagenin A diglucoside ( 2 ) are reported in this study for the first time. All the isolated compounds were evaluated for their anti- Helicobacter pylori , anti-oxidant, and anti-inflammatory activities. In the anti- Helicobacter pylori activity assay, compound 2 showed weak anti- H. pylori activity with 7.8% inhibition. All the isolated compounds showed significant ABTS radical scavenging activity. However, all isolates failed to show inhibitory activity against nitric oxide (NO) production in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. This study demonstrated the experimental support that the W. somnifera root is rich in withanolides, and it can be a valuable natural resource for bioactive withanolides.

Background: The current therapeutic antibodies and chimeric antigen receptor (CAR) T cells are capable of recognizing surface antigens, but not of intracellular proteins, thus limiting the target coverage for drug development. To mimic the feature of T-cell receptor (TCR) that recognizes the complex of major histocompatibility class I and peptide on the cell surface derived from the processed intracellular antigen, we used NY-ESO-1, a cancer-testis antigen, to develop a TCR-like fully human IgG1 antibody and its derivative, CAR-T cells, for cancer immunotherapy., Methods: Human single-chain variable antibody fragment (scFv) phage library (~10 ∧11 ) was screened against HLA-A2/NY-ESO-1 (peptide 157-165) complex to obtain target-specific antibodies. The specificity and affinity of those antibodies were characterized by flow cytometry, ELISA, biolayer interferometry, and confocal imaging. The biological functions of CAR-T cells were evaluated against target tumor cells in vitro. In vivo antitumor activity was investigated in a triple-negative breast cancer (TNBC) model and primary melanoma tumor model in immunocompromised mice., Results: Monoclonal antibody 2D2 identified from phage-displayed library specifically bound to NY-ESO-1 157-165 in the context of human leukocyte antigen HLA-A*02:01 but not to non-A2 or NY-ESO-1 negative cells. The second-generation CAR-T cells engineered from 2D2 specifically recognized and eliminated A2+/NY-ESO-1+tumor cells in vitro, inhibited tumor growth, and prolonged the overall survival of mice in TNBC and primary melanoma tumor model in vivo., Conclusions: This study showed the specificity of the antibody identified from human scFv phage library and demonstrated the potential antitumor activity by TCR-like CAR-T cells both in vitro and in vivo, warranting further preclinical and clinical evaluation of the TCR-like antibody in patients. The generation of TCR-like antibody and its CAR-T cells provides the state-of-the-art platform and proof-of-concept validation to broaden the scope of target antigen recognition and sheds light on the development of novel therapeutics for cancer immunotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The facile and cost-effective fabrication of hybrid nanostructures comprised of hollow mixed metallic chalcogenides has attracted growing interest in the development of high-performance energy storage devices. Herein, multi-component (nickel-cobalt-copper-sulfides/selenides (NCCS/NCCSe)) hollow nanocubes (HNCs) are prepared via a single-step sulfurization/selenization process. The NCCS material shows interior HNCs, and the NCCSe material exhibits slightly formed porous cubes. Both the prepared materials demonstrate higher charge storage performance than the precursor NCC NCs owing to the improved surface morphology and addition of sulfur and selenium ions. Particularly, the NCCS HNCs electrode reveals superior specific capacity (capacitance) (70.32 mAh g -1 (666.20 F g -1 ) at 5 mA cm -2 ) along with excellent cycling stability of 108.6% even after 10 000 cycles. Interestingly, the electrode delivers a good rate capability of 83.5% at a high current density of 20 mA cm -2 . The feasibility of the battery-type NCCS HNCs as a positive electrode is explored by constructing an aqueous electrochemical hybrid capacitor (AEHC). The AEHC exhibits maximum energy and power densities of 23.15 Wh kg -1 and 7899.08 W kg -1 , respectively. Remarkably, it demonstrates superior long-life cycling stability even after 10 000 cycles (120.6% retention). The suitability of AEHC for practical application is also tested by driving electronic devices., (© 2022 Wiley-VCH GmbH.)

Evolving cost-effective transition metal phosphides (TMPs) using general approaches for energy storage is pivotal but challenging. Besides, the absence of noble metals and high electrocatalytic activity of TMPs allow their applicability as catalysts in oxygen evolution reaction (OER). Herein, CoNiP-CoP 2 (CNP-CP) composite is in situ deposited on carbon fabric by a one-step hydrothermal technique. The CNP-CP reveals hybrid nanoarchitecture (3D-on-1D HNA), i.e., cashew fruit-like nanostructures and nanocones. The CNP-CP HNA electrode delivers higher areal capacity (82.8 μAh cm -2 ) than the other electrodes. Furthermore, a hybrid cell assembled with CNP-CP HNA shows maximum energy and power densities of 31 μWh cm -2 and 10.9 mW cm -2 , respectively. Exclusively, the hybrid cell demonstrates remarkable durability over 30 000 cycles. In situ/operando X-ray absorption near-edge structure analysis confirms the reversible changes in valency of Co and Ni elements in CNP-CP material during real-time electrochemical reactions.  Besides, a quasi-solid-state device unveils its practicability by powering electronic components. Meanwhile, the CNP-CP HNA verifies its higher OER activity than the other catalysts by revealing lower overpotential (230 mV). Also, it exhibits relatively small Tafel slope (38 mV dec -1 ) and stable OER activity over 24 h. This preparation strategy may initiate the design of advanced TMP-based materials for multifunctional applications., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Circulating protein biomarkers have demonstrated utility as a diagnostic tool in predicting musculoskeletal disease severity, but their utility in the evaluation of shoulder lesions associated with shoulder instability is unknown. Thus, the purpose of this exploratory study was to determine whether preoperative biomarkers of cartilage turnover and inflammation are associated with specific shoulder lesions in shoulder instability. Thirty-three patients (29.9 ± 9.4 years of age, 4.5 ± 4.7 dislocations) undergoing surgical treatment for shoulder instability were assessed for the presence or absence of associated shoulder lesions. Biomarkers including cartilage oligomeric matrix protein (COMP), C-reactive protein (HS-CRP), interleukin-8 (IL-8), and macrophage inflammatory protein-1 β (MIP-1b) were collected at the time of surgery. Patients with Hill-Sachs lesions had a 31% increase in COMP plasma levels ( p =0.046). No other significant differences were observed for COMP, HS-CRP, IL-8, and MIP-1b with any shoulder lesion including Hill-Sachs lesions, capsular injuries, bony Bankart lesions, and SLAP lesions. In conclusion, inflammatory biomarkers including HS-CRP, IL-8, and MIP-1b were not associated with specific shoulder lesions, while biomarkers of cartilage turnover (COMP) were only elevated in Hill-Sachs lesions. These findings suggest that these biomarkers may have limited utility as prognostic indicators in patients with shoulder instability, though large-scale and longitudinal studies are still necessary., Competing Interests: Dr. Mendias reports research support from GlaxoSmithKline, consultant fees from GLG Consulting, editorial board for Journal of Applied Physiology, Journal of Orthopaedic Research, and Translational Sports Medicine, board member for National Athletic Trainers' Association, and employee for Myognosis. Dr. Rodeo reports consulting fees from Novartis Pharmaceuticals and faculty/speaker fees from Smith & Nephew. Dr. Dines reports consulting fees from Arthrex, Linvatec, Merck Sharpe & Dohme, Trice Medical, Wright Medical Technology, Conmed, and investment in ViewFi Health. No other author has any commercial associations (eg., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2022 Jonathan S. Yu et al.)

A bifunctional silyl reagent Me 2 (CH 2 [double bond, length as m-dash]CH)SiCN has been developed as a novel ethylene equivalent for the Diels-Alder (DA) reaction. The use of this reagent enables the controllable synthesis of value-added cyclohexenyl ketones or 2-acyl cyclohexancarbonitrile derivatives through a five- or six-step tandem sequence based on a Wittig/cyanosilylation/DA reaction/ retro -cyanosilylation/isomerization sequence that involves a temporary silicon-tethered intramolecular DA reaction., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line., Patients and Methods: Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts. Eligibility criteria included a qualifying surgical resection or minimal tumor size, ≤ 4-mg dexamethasone daily dose, and Karnofsky score ≥70. Vaccine treatment consisted of two phases: an induction phase with vaccine given weekly for 4 weeks, and a maintenance phase with vaccines administered every 8 weeks until depletion of supply or disease progression. Patients with newly diagnosed GBM also received standard-of-care radiation and temozolomide. The primary objective for this open-label, single-institution trial was to assess the safety and tolerability of the autologous DC vaccine., Results: For the 11 patients with newly diagnosed GBM, median progression-free survival (PFS) was 8.75 months, and median overall survival was 20.36 months. For the 25 patients with recurrent GBM, median PFS was 3.23 months, 6-month PFS was 24%, and median survival was 11.97 months. A subset of patients developed a cytotoxic T-cell response as determined by an IFNγ ELISpot assay., Conclusions: In this trial, treatment of newly diagnosed and recurrent GBM with autologous DC vaccine pulsed with lysate derived from an allogeneic stem-like cell line was safe and well tolerated. Clinical outcomes add to the body of evidence suggesting that immunotherapy plays a role in the treatment of GBM., (©2021 American Association for Cancer Research.)

Based on electron-positron collision data collected with the BESIII detector operating at the Beijing Electron-Positron Collider II storage rings, the value of R≡σ(e^{+}e^{-}→hadrons)/σ(e^{+}e^{-}→μ^{+}μ^{-}) is measured at 14 center-of-mass energies from 2.2324 to 3.6710 GeV. The resulting uncertainties are less than 3.0% and are dominated by systematic uncertainties.

A solid electrolyte interphase (SEI) on a sodium (Na) metal anode strongly affects the Na deposition morphology and the cycle life of Na metal batteries (SMBs). SMB applications are hindered by an unstable SEI and dendrite growth on the Na anode surface, which directly cause low coulombic efficiency and can even lead to safety issues. An artificial interface layer can stabilize Na metal anodes, be easily tailored, and is barely affected by electrochemical processes. In this review, recent advances that support the stability of working Na metal anodes are focused via artificial interphase engineering of inorganic materials, organic materials, and organic-inorganic composite materials, with an emphasis on the significance of interface engineering in SMBs. Fundamental investigations of artificial interphase engineering are also discussed on Na metal anodes and some recent research is summarized to enhance the interface between Na metal and electrolytes using an artificial interface layer. The prospects for interphase chemistry for Na metal anodes are provided to open a way to safe, high-energy, next-generation SMBs., (© 2021 Wiley-VCH GmbH.)

Purpose: Low-grade glioma (LGG) exhibits longer median survival than high-grade brain tumors, and thus impact of our therapies on patient quality of life remains a crucial consideration. This study evaluated the effects of concurrent temozolomide-based chemoradiation (RT + TMZ) or observation on quality of life (QOL) in patients with low-grade glioma., Methods: We completed a retrospective cross-sectional study of adults with LGG who underwent surgery with known molecular classification from 1980 to 2018. Postoperatively, patients were either observed or received adjuvant concurrent temozolomide-based chemoradiation. EQ-5D and PHQ-9 depression screen were completed before outpatient visits every 2-3 months. Baseline score was defined as ± 30 days within initial operation., Results: Of the 63 patients (mean age 44 ± 17 years, 51% female) with baseline EQ-5D or PHQ-9 depression screen data and at least one follow-up measure, 30 (48%) were observed and 33 (52%) received RT + TMZ. No significant decline was seen in EQ-5D or PHQ-9 scores at 3, 6, 9, 12, and 24 months compared to baseline scores for all patients. At each time point, there was no significant difference between those who were observed or received adjuvant therapy. The linear mixed model estimating PHQ-9 value or EQ-5D index demonstrated that there was no significant difference in PHQ-9 or EQ-5D index between treatment groups (p = 0.42 and p = 0.54, respectively) or time points (p = 0.24 and p = 0.99, respectively)., Conclusion: Our study found no significant decline in patient QOL or depression scores as assessed by patient- reported outcome measures for patients with low-grade glioma up to 2 years following surgery. We found no difference between RT + TMZ compared to observation during this time frame. Additional follow-up can help identify the longer-term impact of treatment strategy on patient experience., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Here, we describe a novel interaction between the RNA helicase DDX3 and the deubiquitinase ubiquitin-specific peptidase 9 X-linked (USP9X) in human cells. Domain mapping studies reveal that the C-terminal region of DDX3 interacted with the N terminus of USP9X. USP9X was predominantly localized in the cytoplasm where the interaction between DDX3 and USP9X occurred. USP9X was not visibly enriched in cytoplasmic stress granules (SGs) under oxidative stress conditions, whereas overexpression of GFP-DDX3 induced SG formation and recruited USP9X to SGs in HeLa cells. Luciferase reporter assays showed that depletion of USP9X had no significant effect on DDX3-mediated translation. Given that DDX3 is not ubiquitinated upon ubiquitin overexpression, it is unlikely that DDX3 serves as a substrate of USP9X. Importantly, we found that ubiquitinated MCL1 was accumulated upon depletion of USP9X and/or DDX3 in MG132-treated cells, suggesting that USP9X and DDX3 play a role in regulating MCL1 protein stability and anti-apoptotic function. This study indicates that DDX3 exerts anti-apoptotic effects probably by coordinating with USP9X in promoting MCL1 deubiquitination., (© 2021 Federation of European Biochemical Societies.)

Phenalenone derivatives sourced from fungi are polyketides that have attracted significant interest because of their diverse chemical structures and potential bioactivities. As part of our ongoing quest to discover novel natural products with biological properties from diverse natural resources, three unreported phenalenone derivatives (1-3), named ent-12-methoxyisoherqueinone (1), (-)-scleroamide (2), and (+)-scleroamide (3), together with four known phenalenone derivatives, ent-atrovenetinone (4), isoherqueinone (5), herqueinone (6), and ent-peniciherquinone (7) were isolated from the Hawaiian soil fungus Penicillium herquei FT729, collected on the Big Island, Hawaii. Compounds 2 and 3 were enantiomers, which were separated using a chiral-phase HPLC column, which provided optically pure compounds 2 and 3. The structures of the novel compounds were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution ESIMS. Their absolute configurations were determined using quantum chemical electronic circular dichroism (ECD) calculations. The inhibitory activity of the isolated compounds (1-7) against indoleamine 2,3-dioxygenase 1 (IDO1) was assessed. Compounds 1, 5-7 inhibited IDO1, with IC 50 values of 32.59, 36.86, 19.05, and 24.18 μM, respectively. These findings demonstrated that the phenalenone derivatives 1 and 5-7, as IDO1 inhibitors, are promising anticancer immunotherapeutic agents., (© 2022. The Pharmaceutical Society of Korea.)

Introduction: The coronavirus disease 2019 (COVID-19) heralded an unprecedented increase in telemedicine utilization. Our objective was to assess patient satisfaction with telemedicine during the COVID-19 era. Methods: Telemedicine visit data were gathered from Stanford Health Care (Stanford) and the Hospital for Special Surgery (HSS). Patient satisfaction data from HSS were captured from a Press-Ganey questionnaire between April 19, 2020, and December 12, 2020, whereas Stanford data were taken from a novel survey instrument that was distributed to all patients between June 22, 2020, and November 1, 2020. Participants: There were 60,550 telemedicine visits at Stanford, each linked with a postvisit survey. At HSS, there were 66,349 total telemedicine visits with 7,348 randomly linked with a postvisit survey. Main Outcomes and Measures: Two measures of patient satisfaction were used for this study: (1) a patient's "overall visit score" and (2) whether the patient indicated the highest possible "likelihood to recommend" (LTR) score (LTR top box score). Results: The LTR top box percentage at Stanford increased from 69.6% to 74.0% ( p  = 0.0002), and HSS showed no significant change (p = 0.7067). In the multivariable model, the use of a cell phone (adjusted odds ratio [aOR]: 1.18; 95% confidence interval [CI]: 1.12-1.23) and tablet (aOR: 1.15; 95% CI: 1.07-1.23) was associated with higher overall scores, whereas visits with interrupted connections (aOR: 0.49; 95% CI: 0.42-0.57) or help required to connect (aOR: 0.49; 95% CI: 0.42-0.56) predicted lower patient satisfaction. Conclusions: We present the largest published description of patient satisfaction with telemedicine, and we identify important telemedicine-specific factors that predict increased overall visit score. These include the use of cell phones or tablets, phone reminders, and connecting before the visit was scheduled to begin. Visits with poor connectivity, extended wait times, or difficulty being seen, examined, or understood by the provider were linked with reduced odds of high scores. Our results suggest that attention to connectivity and audio/visual definition will help optimize patient satisfaction with future telemedicine encounters.

Compared to most of nano-sized particles, core-shell-structured nanoflowers have received great attention as bioactive materials because of their high surface area with the flower-like structures. In this study, core-shell-structured Si-based NiO nanoflowers, Si@NiO, were prepared by a modified chemical bath deposition method followed by thermal reduction. The crystal morphology and basic structure of the composites were characterized by powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), specific surface area (BET) and porosity analysis (BJT), and inductively coupled plasma optical emission spectrometry (ICP-OES). The electrochemical properties of the Si@NiO nanoflowers were examined through the redox reaction of ascorbic acid with the metal ions present on the surface of the core-shell nanoflowers. This reaction favored the formation of reactive oxygen species. The Si@NiO nanoflowers showed excellent anticancer activity and low cytotoxicity toward the human breast cancer cell line (MCF-7) and mouse embryonic fibroblasts (MEFs), respectively, demonstrating that the anticancer activities of the Si@NiO nanoflowers were primarily derived from the oxidative capacity of the metal ions on the surface, rather than from the released metal ions. Thus, this proves that Si-based NiO nanoflowers can act as a promising candidate for therapeutic applications.

Cancer remains one of the leading causes of death worldwide. Cancer stem cells (CSCs) are the underlying reason for tumor recurrence, progression, and therapeutic resistance. Aptamers are synthetic single-stranded oligonucleotides that can specifically bind to various molecular targets. Here, we aim to develop an effective aptamer-based biomarker and therapeutic tool that targets CSCs for cancer therapy. We perform whole-cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) to screen DNA aptamers that specifically bound to lung CSCs, modeled by E-cadherin-silenced A549 cells. We develop a CSC-specific aptamer (AP-9R) specifically recognizing lung CSCs with high affinity and identify Annexin A2, a Ca 2+ -dependent membrane-binding protein, as its target. Annexin A2 expression was upregulated in lung CSCs and involved in cancer stemness. The expression of Annexin A2 was associated with signatures of stemness and metastasis, as well as poor clinical outcomes, in lung cancer in silico . Moreover, AP-9R decreased Annexin A2 expression and suppressed CSC properties in CSCs in vitro and in vivo . The present findings suggest that Annexin A2 is a CSC marker and regulator, and the CSC-specific aptamer AP-9R has potential theranostic applications for lung cancer., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Molecular networking (MN) has become a popular data analysis method for untargeted mass spectrometry (MS)/MS-based metabolomics. Recently, MN has been suggested as a powerful tool for drug metabolite identification, but its effectiveness for drug metabolism studies has not yet been benchmarked against existing strategies. In this study, we compared the performance of MN, mass defect filtering, Agilent MassHunter Metabolite ID, and Agilent Mass Profiler Professional workflows to annotate metabolites of sildenafil generated in an in vitro liver microsome-based metabolism study. Totally, 28 previously known metabolites with 15 additional unknown isomers and 25 unknown metabolites were found in this study. The comparison demonstrated that MN exhibited performances comparable or superior to those of the existing tools in terms of the number of detected metabolites (27 known metabolites and 22 unknown metabolites), ratio of false positives, and the amount of time and effort required for human labor-based postprocessing, which provided evidence of the efficiency of MN as a drug metabolite identification tool.

Using a data sample corresponding to an integrated luminosity of 2.93  fb^{-1} collected at a center-of-mass energy sqrt[s]=3.773  GeV by the BESIII detector, the decay D^{0}→ωϕ is observed for the first time. The branching fraction is measured to be (6.48±0.96±0.40)×10^{-4} with a significance of 6.3σ, where the first and second uncertainties are statistical and systematic, respectively. An angular analysis reveals that the ϕ and ω mesons from the D^{0}→ωϕ decay are transversely polarized. The 95% confidence level upper limit on longitudinal polarization fraction is set to be less than 0.24, which is inconsistent with current theoretical expectations and challenges our understanding of the underlying dynamics in charm meson decays.

Obesity is a major health problem that is caused by body fat accumulation and that can lead to metabolic diseases. Owing to several side effects of the currently used antiobesity drugs, natural plants have risen as safe and potential candidates to alleviate obesity. We have previously reported the antiobesity effect of Hydrangea serrata (Thunb.) Ser. leaves extract (WHS) and its underlying mechanisms. As an extension of our preclinical studies, this study aimed to investigate the effect of WHS on body weight and body fat reduction in overweight or obese humans. A total of 93 healthy overweight or obese males and females, aged 19-65 years, with body mass indexes (BMIs) ≥ 25 and <32 kg/m 2 , were recruited and received either an oral administration of 600 mg of WHS, or placebo tablets for 12 weeks. Daily supplementation with WHS decreased body weights, body fat masses, and BMIs compared with the placebo-treated group. The hip circumferences, visceral fat areas, abdominal fat areas, and visceral-to-subcutaneous ratios decreased after WHS supplementation. No significant side effects were observed during or after the 12 weeks of WHS intake. In conclusion, WHS, which has beneficial effects on body weight and body fat reduction, could be a promising antiobesity supplement that does not produce any side effects.

Metabolomics, which serves as a readout of biological processes and diseases monitoring, is an informative research area for disease biomarker discovery and systems biology studies. In particular, reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) has become a powerful and popular tool for metabolomics analysis, enabling the detection of most metabolites. Very polar and ionic metabolites, however, are less easily detected because of their poor retention in RP columns. Dansylation of metabolites simplifies the sub-metabolome analysis by reducing its complexity and increasing both hydrophobicity and ionization ability. However, the various metabolite concentrations in clinical samples have a wide dynamic range with highly individual variation in total metabolite amount, such as in saliva. The bicarbonate buffer typically used in dansylation labeling reactions induces solvent stratification, resulting in poor reproducibility, selective sample loss and an increase in false-determined metabolite peaks. In this study, we optimized the dansylation protocol for samples with wide concentration range of metabolites, utilizing diisopropylethylamine (DIPEA) or tri-ethylamine (TEA) in place of bicarbonate buffer, and presented the results of a systemic investigation of the influences of individual processes involved on the overall performance of the protocol. In addition to achieving high reproducibility, substitution of DIPEA or TEA buffer resulted in similar labeling efficiency of most metabolites and more efficient labeling of some metabolites with a higher pK a . With this improvement, compounds that are only present in samples in trace amounts can be detected, and more comprehensive metabolomics profiles can be acquired for biomarker discovery or pathway analysis, making it possible to analyze clinical samples with limited amounts of metabolites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Importance: Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu)., Objective: To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment. Additionally, potential risk factors associated with these adverse events were evaluated., Design, Setting, and Participants: This cohort study included patients with neovascular age-related macular degeneration in the Intelligent Research in Sight (IRIS) Registry and Komodo Healthcare Map. Patients initiating and receiving 1 or more brolucizumab injections from October 8, 2019, to June 5, 2020, with up to 6 months of follow-up were included., Intervention: Brolucizumab injections., Main Outcome and Measures: Incidence of IOI (including RV) and/or RO and RV and/or RO and risk stratification for the identified risk factors., Results: Of 10 654 and 11 161 included eyes (from the IRIS Registry and Komodo Health database, respectively), the median follow-up times were 97 and 95 days. Most eyes switched from another anti-vascular endothelial growth factor agent (9686 of 10 654 [90.9%] and 10 487 of 11 161 [94.0%], respectively), most commonly aflibercept (7160 of 9686 [73.9%] and 7156 of 10 487 [68.2%]), and most were from women (6105 of 10 654 [57.3%] and 6452 of 11 161 [57.8%]). The overall incidence of IOI and/or RO was 2.4% (255 of 10 654 eyes) and 2.4% (268 of 11 161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10 654 eyes and 63 of 11 161 eyes), respectively. Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets). There was an increased estimated incidence rate in women (2.9% [95% CI, 2.5%-3.3%] and 3.0% [95% CI, 2.6%-3.4%]) compared with men (1.3% [95% CI, 1.0%-1.7%] and 1.4% [95% CI, 1.0%-1.7%]), but this risk was not as large as that of a prior IOI and/or RO. Similar findings were observed for patients with RV and/or RO events., Conclusions and Relevance: The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first brolucizumab injection had the highest observed risk rate for IOI and/or RO in the early months after the first brolucizumab treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with brolucizumab cannot be assessed.

The COVID-19 pandemic has accelerated neurological, mental health disorders, and neurocognitive issues. However, there is a lack of inexpensive and efficient brain evaluation and screening systems. As a result, a considerable fraction of patients with neurocognitive or psychobehavioral predicaments either do not get timely diagnosed or fail to receive personalized treatment plans. This is especially true in the elderly populations, wherein only 16% of seniors say they receive regular cognitive evaluations. Therefore, there is a great need for development of an optimized clinical brain screening workflow methodology like what is already in existence for prostate and breast exams. Such a methodology should be designed to facilitate objective early detection and cost-effective treatment of such disorders. In this paper we have reviewed the existing clinical protocols, recent technological advances and suggested reliable clinical workflows for brain screening. Such protocols range from questionnaires and smartphone apps to multi-modality brain mapping and advanced imaging where applicable. To that end, the Society for Brain Mapping and Therapeutics (SBMT) proposes the Brain, Spine and Mental Health Screening (NEUROSCREEN) as a multi-faceted approach. Beside other assessment tools, NEUROSCREEN employs smartphone guided cognitive assessments and quantitative electroencephalography (qEEG) as well as potential genetic testing for cognitive decline risk as inexpensive and effective screening tools to facilitate objective diagnosis, monitor disease progression, and guide personalized treatment interventions. Operationalizing NEUROSCREEN is expected to result in reduced healthcare costs and improving quality of life at national and later, global scales.

Since the end of 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The RNA genome of SARS-CoV-2, which is highly infectious and prone to rapid mutation, encodes both structural and nonstructural proteins. Vaccination is currently the only effective method to prevent COVID-19, and structural proteins are critical targets for vaccine development. Currently, many vaccines are in clinical trials or are already on the market. This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19, including viral vector vaccines, DNA vaccines, RNA vaccines, live-attenuated vaccines, inactivated virus vaccines, recombinant protein vaccines and bionic nanoparticle vaccines. In addition to traditional inactivated virus vaccines, some novel vaccines based on viral vectors, nanoscience and synthetic biology also play important roles in combating COVID-19. However, many challenges persist in ongoing clinical trials., (© 2021. The Author(s).)

An ion-exchange process is a promising approach to design advanced electrode materials for high-performance energy storage devices. Herein, a nanostructured Ni 3 Sn 2 S 2 -CoS (NSS-CS) composite is fabricated by successive hydrothermal and ion-exchange processes. Since the incorporation of redox-rich cobalt element enables the NSS-CS composite to be more electrochemically active, its impact on the electrochemical performance is therefore extensively studied. Particularly, the NSS-CS-0.2 g electrode material delivered a high areal capacity of 830.4 µAh cm -2 at 5 mA cm -2 . Additionally, a room-temperature wet-chemical approach is employed to anchor nanosilver (nAg)-particles on the NSS-CS-0.2 g (nAg@NSS-CS-0.2 g) to further exalt its electrokinetics. Consequently, the nAg@NSS-CS-0.2 g electrode shows a higher areal capacity of 948.5 µAh cm -2 (193.5 mAh g -1 ) than that of the NSS-CS-0.2 g. Furthermore, its practicability is also examined by assembling a hybrid cell. The assembled hybrid cell delivers a high areal capacity of 969.2 µAh cm -2 (49.2 mAh g -1 ) at 7 mA cm -2 and maximum areal energies and power densities of 0.784 mWh cm -2 (40.8 Wh kg -1 ) and 45 mW cm -2 (2347.4 W kg -1 ), respectively. The efficiency of the hybrid cells is also tested by harvesting solar energy, followed by energizing electronic components. This work can pave the way for significant attraction in designing advanced electrodes for energy-related fields., (© 2021 Wiley-VCH GmbH.)

Background: This study aimed to analyze non-coding RNA sequencing results, screen differentially expressed long non-coding RNAs (lncRNAs), and predict lncRNA target genes. It further clarifies the potential functions of lncRNAs, thus exploring potential biomarkers and therapeutic targets for stroke., Methods: LncRNA sequencing data of blood samples from stroke patients and healthy subjects ( GSE102541 and GSE140275 ) were downloaded from the Gene Expression Omnibus (GEO) database. This study used R software and related R packages to conduct a batch correction and differential analysis of sequencing results. It also screened differentially expressed lncRNAs and visualized the correlations between significantly different lncRNAs. Target genes of differential lncRNAs were predicted by the StarBase database. Gene ontology (GO) functional enrichment analysis of related target genes was performed using the DAVID database. Principal component analysis was performed based on the expression levels of lncRNAs with the most significant differences in stroke blood samples., Results: A total of 239 differentially expressed lncRNAs were screened out in this study, of which 146 were upregulated and 93 were downregulated. According to |log2FC| values from highest to lowest, the top 10 lncRNAs with the most significant differences were selected. The upregulated lncRNAs were LINC02334 , TARID , MRGPRF-AS1 , CAI2 , LINC00189 , TUG1 , and RNF5P1 . The downregulated lncRNAs included AC005180.2 , ADAMTS9-AS1 , and AC036108.3 . TARID was strongly correlated with MRGPRF-AS1 . Meanwhile, LINC02334 was strongly correlated with TUG1 . CAI2, LINC00189 , and RNF5P1 were at the core of the correlation network and may therefore be the critical lncRNAs in stroke pathogenesis. GO functional enrichment results indicated that genes were significantly enriched in muscle contraction, RNA polymerase II promoter transcription regulation, muscle structure composition, focal adhesion, endothelial cell chemotaxis, actin, actin cytoskeleton, actin filament binding, blood lipid regulation, smooth muscle contraction regulation, skeletal muscle cell differentiation, and other functions. Principal component analysis showed that the 10 lncRNAs with significant differences could significantly distinguish stroke blood samples from healthy control blood samples, and could characterize the essential characteristics of stroke., Conclusions: LINC02334, TARID, MRGPRF-AS1, CAI2, LINC00189, TUG1, RNF5P1, AC005180.2, ADAMTS9-AS1 , and AC036108.3 play an essential role in the pathogenesis of stroke, and may be potential therapeutic targets., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-5815). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Although microbioa-based therapies have shown putative effects on the treatment of non-alcoholic fatty liver disease (NAFLD), it is not clear how microbiota-derived metabolites contribute to the prevention of NAFLD. We explored the metabolomic signature of Lactobacillus lactis and Pediococcus pentosaceus in NAFLD mice and its association in NAFLD patients., Methods: We used Western diet-induced NAFLD mice, and L. lactis and P. pentosaceus were administered to animals in the drinking water at a concentration of 10 9 CFU/g for 8 weeks. NAFLD severity was determined based on liver/body weight, pathology and biochemistry markers. Caecal samples were collected for the metagenomics by 16S rRNA sequencing. Metabolite profiles were obtained from caecum, liver and serum. Human stool samples (healthy control [n = 22] and NAFLD patients [n = 23]) were collected to investigate clinical reproducibility for microbiota-derived metabolites signature and metabolomics biomarker., Results: L. lactis and P. pentosaceus supplementation effectively normalized weight ratio, NAFLD activity score, biochemical markers, cytokines and gut-tight junction. While faecal microbiota varied according to the different treatments, key metabolic features including short chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites were analogously restored by both probiotic supplementations. The protective effects of indole compounds were validated with in vitro and in vivo models, including anti-inflammatory effects. The metabolomic signatures were replicated in NAFLD patients, accompanied by the comparable levels of Firmicutes/Bacteroidetes ratio, which was significantly higher (4.3) compared with control (0.6). Besides, the consequent biomarker panel with six stool metabolites (indole, BAs, and SCFAs) showed 0.922 (area under the curve) in the diagnosis of NAFLD., Conclusions: NAFLD progression was robustly associated with metabolic dys-regulations in the SCFAs, bile acid and indole compounds, and NAFLD can be accurately diagnosed using the metabolites. L. lactis and P. pentosaceus ameliorate NAFLD progression by modulating gut metagenomic and metabolic environment, particularly tryptophan pathway, of the gut-liver axis., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Antibiotic-resistant infections are a growing problem; to combat multi-drug resistant bacterial infections, antibiotics with novel mechanisms of action are needed. Identification of potent bioactive natural products is an attractive avenue for developing novel therapeutic strategies against bacterial infections. As part of our ongoing research to explore bioactive natural products from diverse resources, we investigated the antimicrobial compounds from Woodfordia uniflora , a flowering shrub unique to the Dhofar region of Oman. The plant has been used as a remedy for skin infections in Oman. However, to date, no study has examined the antimicrobial compounds in W. uniflora . Phytochemical analysis of the methanolic extract of W. uniflora leaves in combination with LC/MS-based analysis allowed us to isolate and identify four flavonoid-type analogs ( 1-4 ), procyanidin B3-3- O -gallate ( 1 ), rhamnetin 3- O -(6″-galloyl)-β-D-glucopyranoside ( 2 ), rhamnetin 3- O -α-L-rhamnopyranoside ( 3 ), and quercetin 3- O -(6″-galloyl)-β-D-glucopyranoside ( 4 ). The isolates have a novel mechanism of action; the compounds inhibit biofilm formation in methicillin-resistant Staphylococcus aureus (MRSA) and synergize with methicillin. Our metabolite analysis revealed that this synergizing activity by compounds was achieved by remodeling metabolism including central carbon metabolism and glutamine biosynthesis that resulted in abnormal cell formation and reduction in biofilm formation of MRSA. Taken together, these findings provide experimental evidence that rhamnetin 3- O -(6″-galloyl)-β-D-glucopyranoside ( 2 ) and quercetin 3- O -(6″-galloyl)-β-D-glucopyranoside ( 4 ) can be considered as potential therapeutic agents for the treatment of methicillin-resistant S. aureus -associated diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Kim, Rashan, Kim, Lee and Kim.)

We present a security device that can detect and block hacking using the characteristics of liquid crystals. This device is based on a liquid crystal cell consisting of a uniformly aligned layer and a photo-alignment layer. To inscribe a pattern, the device is illuminated when the liquid crystal is in the smectic phase. The resulting image is invisible after light irradiation. Heating to the nematic phase improves this alignment and reveals the recorded pattern. Returning to the smectic phase distorts the pattern. Because the pattern is not shown without heating and the trace of the pattern does not disappear once viewed, it is possible to detect whether data has been hacked. The device is easy to fabricate, cost-effective, and sensitive to outside intrusion.

Naja atra , also known as Taiwanese cobra, is one of the most prevalent venomous snakes in Taiwan. Clinically, freeze-dried neurotoxic antivenom (FNAV) produced from horses by Taiwan Centers for Disease Control (CDC) has been the only approved treatment for N. atra envenoming for the last few decades. During antivenom production, large numbers of mice are used in the in vivo assay to determine whether the neutralization potency of hyperimmunized equines is satisfactory for large-scale harvesting. However, this in vivo assay is extremely laborious, expensive, and significantly impairs animal welfare. In the present study, we aimed to develop an in vitro ELISA-based system that could serve as an alternative assay to evaluate the neutralization potency of plasma from hyperimmunized equines. We initially obtained 51 plasma samples with known (high or low) neutralization potency assessed in vivo from 9 hyperimmunized equines and subsequently determined their antibody titers against the five major protein components of N. atra venom (neurotoxin (NTX), phospholipase A2 (PLA 2 ), cytotoxin (CTX), cysteine-rich secretory protein (CRISP), and snake venom metalloproteinase (SVMP)) via ELISA. The antibody titer against NTX was the most effective in discriminating between high and low potency plasma samples. To identify the specific epitope(s) of NTX recognized by neutralization potency-related antibodies, 17 consecutive NTX-derived pentadecapeptides were synthesized and used as antigens to probe the 51 equine plasma samples. Among the 17 peptides, immunoreactive signals for three consecutive peptides (NTX1-8, NTX1-9, and NTX1-10) were significantly higher in the high potency relative to low potency equine plasma groups ( p < 0.0001). Our ELISA system based on NTX1-10 peptide (RWRDHRGYRTERGCG) encompassing residues 28-42 of NTX displayed optimal sensitivity (96.88%) and specificity (89.47%) for differentiating between high- and low-potency plasma samples (area under the receiver operating characteristic curve (AUC) = 0.95). The collective data clearly indicate that the antibody titer against NTX protein or derived peptides can be used to efficiently discriminate between high and low neutralization potency of plasma samples from venom-immunized horses. This newly developed antibody detection ELISA based on NTX or its peptide derivatives has good potential to complement or replace the in vivo rodent assay for determining whether the neutralization potency of equine plasma is satisfactory for large-scale harvesting in the antivenom production process against N. atra.

Here, we report an unprecedented catalytic enantioselective cyanation of ketonitrones enabled by the bifunctional cyanating reagent Me 2 (CH 2 Cl)SiCN. This approach allows facile access to optically active N -hydroxyl-α-amino nitriles that are of high synthetic value but difficult to acquire by other methods. The use of bifunctional cyanating reagent Me 2 (CH 2 Cl)SiCN not only achieves an enantioselectivity higher than that with TMSCN but also enables various diversification reactions of the resulting silylated adducts. This represents the first enantioselective catalytic nucleophilic addition reaction of unactivated ketone-derived nitrones, exhibiting the potential of such tetrasubstituted C═N bonds for asymmetric synthesis of N -hydroxy α-amino acids and other N -hydroxy tertiary amines.

Through a solid-phase reaction technique, Sm 3+ and Bi 3+ co-doped La 3 BWO 9 phosphors with high emission intensity and sensitive temperature sensing properties have been successfully synthesized. Based on XRD Rietveld refinement, the optimized crystal structure was used as the original model to calculate the band structure and partial density of states (PDOS) by density functional theory (DFT) calculations. The luminescence characteristics of Sm 3+ and Bi 3+ co-doped La 3 BWO 9 phosphors were measured and analyzed. In addition, the optimal doping concentrations of Sm 3+ and Bi 3+ were investigated. The luminescence properties of Sm 3+ doped phosphors were optimized by introducing Bi 3+ ions. Efficient energy transfer from Bi 3+ to Sm 3+ ions was observed in La 3 BWO 9 :Sm 3+ , Bi 3+ phosphors. An optical temperature sensor with high sensitivity was designed based on the different thermal quenching properties of Sm 3+ and Bi 3+ ions. In the temperature range of 293-498 K, the optimum absolute sensitivity ( S a ) and maximum relative sensitivity ( S r ) were 2.88 %K -1 and 1.32 %K -1 , respectively. These results indicated that the prepared La 3 BWO 9 :Bi 3+ , Sm 3+ phosphors have wide application prospects as solid state lighting materials and optical temperature sensors.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been accompanied by significant reductions in patient volumes for non-COVID-19-related conditions ranging from acute coronary syndrome to ischemic strokes to acute trauma. However, the impact of the COVID-19 pandemic on patient volumes for a broad range of orthopedic conditions remains unknown. The purpose of this study was to investigate the association of the COVID-19 pandemic with changes in patient volumes of 35 emergent (e.g. dislocations, open fractures), urgent (e.g. fractures), and nonurgent orthopedic conditions (e.g. osteoarthritis, sprains)., Methods: A retrospective interrupted time-series analysis of patient volumes was conducted for 35 orthopedic conditions based on ICD-10 diagnosis codes. Patient hospitalizations and new problem visits were aggregated across two institutions in New York state, including one urban tertiary care orthopedic hospital, one urban academic medical center, and all state outpatient facilities affiliated with the orthopedic institution. Patient volumes in the COVID-19 peak period (03/2020-05/2020) and COVID-19 recovery period (06/2020-10/2020) were compared against pre-COVID-19 vol (01/2018-02/2020)., Results: Overall, 169,047 cases were included in the analysis across 35 conditions with 3775 emergent cases, 6376 urgent cases, and 158,896 nonurgent cases . During the COVID-19 peak period, patient caseloads for 1 out of 7 emergent conditions (p = 0.02) and 26 out of 28 urgent and nonurgent conditions (p < 0.05) were significantly reduced compared to the pre-COVID-19 period. During the COVID-19 recovery period, patient volumes in 3 out of 13 emergent and urgent conditions (p < 0.03) and 11 out of 22 nonurgent conditions (p < 0.04) were decreased compared to pre-COVID-19 vol., Conclusions: This study found that the pandemic was associated with considerable changes in patient patterns for non-COVID-19 orthopedic conditions. The long-term effects of patient volume reductions on both patient outcomes and orthopedic health systems remain to be seen., Level of Evidence: Cohort study; level of evidence IV., Competing Interests: The authors have no conflicts of interest to declare. No author has any relevant financial interests, activities, relationships, and/or affiliations., (© 2021 Delhi Orthopedic Association. All rights reserved.)

Aim: To evaluate the prevalence of self-directed cannabidiol (CBD) use in patients with end-stage degenerative hip and knee arthritis who underwent total hip arthroplasty and total knee arthroplasty. Materials & methods: Anonymous surveys for 109 patients were completed at 6 weeks follow-up after either total hip arthroplasty or total knee arthroplasty at a single tertiary care US orthopedic hospital. Results: Within the perioperative window encompassing both preoperative and postoperative periods, 22% (95% CI: 14-30%) of patients used CBD. Conclusion: There was no difference in pain satisfaction between patients who used CBD and patients who did not. Given high rates of self-directed perioperative CBD use and the mixed body of evidence, further research is needed to better understand whether CBD is safe and effective.

Objectives: This study aimed to elucidate the relationship between gadoxetic acid-enhanced magnetic resonance imaging (MRI) features-enhancing capsule, corona enhancement or hypointense rim-observed in hepatocellular carcinomas (HCCs)., Methods: Of the HCCs surgically confirmed during a 5-year period (2013-2017), ≤ 3-cm lesions (n = 83) in 78 patients were evaluated. Presence of corona enhancement and enhancing capsule on multiphasic dynamic imaging and presence of hypointense rim on hepatobiliary phase imaging were determined retrospectively by two independent observers. The relationship among the three imaging features was statistically analysed and correlated with the presence of histologic fibrous capsules, tumour differentiation and gross morphologic type., Results: There was substantial overall interobserver agreement in determining the presence of the three imaging features. Sixty (72.3%) lesions had histologic fibrous capsule positively correlated with all three imaging features (p < 0.05). Corona enhancement was the most common (66.3%) feature followed by enhancing capsule (61.4%) and hypointense rim (33.7%), and the correspondence rate of enhancing capsule to corona enhancement was 68.6% (p = 0.004). Corona enhancement was more frequently observed in moderately differentiated HCCs than other lesions (p = 0.012) and not dependent (p = 0.465) on the tumour size, while enhancing capsule was significantly dependent on tumour size, as indicated by univariate (p < 0.001) and multivariate analyses (odds ratio, 4.241; p = 0.002)., Conclusions: Among the capsular features, corona enhancement might closely relate to enhancing capsule in HCCs. Corona enhancement was not dependent on tumour size and had the highest incidence of appearance on gadoxetic acid-enhanced multiphasic dynamic MRI., Key Points: • Enhancing capsule has a limited role in the LI-RADS categorisation during gadoxetic acid-enhanced MRI. • Appearance of corona enhancement is closely related to enhancing capsule and is not dependent on size of HCCs. • Corona enhancement can substitute enhancing capsule in the diagnosis of HCCs during multiple arterial and portal venous phase gadoxetic acid-enhanced MRI., (© 2021. European Society of Radiology.)

Using a dataset of 6.32  fb^{-1} of e^{+}e^{-} annihilation data collected with the BESIII detector at center-of-mass energies between 4178 and 4226 MeV, we have measured the absolute branching fraction of the leptonic decay D&#95;{s}^{+}→τ^{+}ν&#95;{τ} via τ^{+}→e^{+}ν&#95;{e}ν[over ¯]&#95;{τ}, and find B&#95;{D&#95;{s}^{+}→τ^{+}ν&#95;{τ}}=(5.27±0.10±0.12)×10^{-2}, where the first uncertainty is statistical and the second is systematic. The precision is improved by a factor of 2 compared to the previous best measurement. Combining with f&#95;{D&#95;{s}^{+}} from lattice quantum chromodynamics calculations or the |V&#95;{cs}| from the CKMfitter group, we extract |V&#95;{cs}|=0.978±0.009±0.012 and f&#95;{D&#95;{s}^{+}}=(251.1±2.4±3.0)  MeV, respectively. Combining our result with the world averages of B&#95;{D&#95;{s}^{+}→τ^{+}ν&#95;{τ}} and B&#95;{D&#95;{s}^{+}→μ^{+}ν&#95;{μ}}, we obtain the ratio of the branching fractions B&#95;{D&#95;{s}^{+}→τ^{+}ν&#95;{τ}}/B&#95;{D&#95;{s}^{+}→μ^{+}ν&#95;{μ}}=9.72±0.37, which is consistent with the standard model prediction of lepton flavor universality.