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Major advances have been made in our understanding of CNS tumors, especially glioma, however, the survival of patients with malignant glioma remains poor. While radiation and chemotherapy have increased overall survival, glioblastoma multiforme (GBM) still has one of the worst 5-year survival rates of all human cancers. Here, in this chapter, the authors review the abrogation of the immune system in the tumor setting, revealing many plausible targets for therapy and the current immunotherapy treatment strategies employed. Notably, glioma has also been characterized as a subset of primary spinal cord tumor and current treatment recommendations are outlined here., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

This study aimed to identify the possible function and the molecular mechanism of hsa_circ_0007334 in human bone marrow mesenchymal stem cells (hBMSCs) osteogenic differentiation. The level of hsa_circ_0007334 was detected by means of quantitative real-time polymerase chain reaction (RT-qPCR). Alkaline phosphatase (ALP), RUNX2, osterix (OSX), and osteocalcin (OCN) were monitored to analyze the degree of osteogenic differentiation under routine culture or under the control of hsa_circ_0007334. The proliferation of hBMSCs was tested with a cell counting kit-8 (CCK-8) assay. The migration of hBMSCs was tested using the Transwell assay. Bioinformatics analysis was used to predict the possible targets of hsa_circ_0007334 or miR-144-3p. Dual-luciferase reporter assay system was used to analyze the combination between hsa_circ_0007334 and miR-144-3p. Hsa_circ_0007334 was upregulated in osteogenic differentiation of hBMSCs. Osteogenic differentiation increased by hsa_circ_0007334 in vitro was confirmed with levels of ALP and bone markers (RUNX2, OCN, OSX). hsa_circ_0007334 overexpression promoted osteogenic differentiation, proliferation, and migration of hBMSCs, and knockdown of hsa_circ_0007334 has the opposite effects. miR-144-3p was identified as the target of hsa_circ_0007334. The targeting genes of miR-144-3p are involved in osteogenic-differentia-tion-related biological processes (such as bone development, epithelial cell proliferation, and mesenchymal cell apoptotic prosess) and pathways (including FoxO and VEGF signaling pathway). Hsa_circ_0007334, therefore, presents itself as a promising biological for osteogenic differentiation.

Dermabacter vaginalis is a human-derived bacterium isolated from vaginal fluid of a Korean female in 2016. Although several human-related species in Dermabacter genus have been reported there are few studies on their bioactive metabolites. Dermazolium A (1), a rare imidazolium metabolite, was isolated from D. vaginalis along with five known metabolites (2-6) and their chemical structures were determined by NMR, HRMS, and MS/MS data analysis. Feeding experiments using predicted precursors and biomimetic total synthesis of 1 corroborated its structure and led to suggestion of biosynthetic pathway of 1. Antibacterial tests on the isolated compounds showed that 1 is a mild antibacterial agent with MIC values of 41 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA) USA300, Lacticaseibacillus paracasei subsp. paracasei KCTC 3510 and Brevibacterium epidermidis KCTC 3090., (© 2023. The Pharmaceutical Society of Korea.)

Extracellular vesicles (EVs) are valuable sources for the discovery of useful cancer biomarkers. This study explores the potential usefulness of tumor cell-derived EV membrane proteins as plasma biomarkers for early detection of colorectal cancer (CRC). EVs were isolated from the culture supernatants of four CRC cell lines by ultracentrifugation, and their protein profiles were analyzed by LC-MS/MS. Bioinformatics analysis of identified proteins revealed 518 EV membrane proteins in common among at least three CRC cell lines. We next used accurate inclusion mass screening (AIMS) in parallel with iTRAQ-based quantitative proteomic analysis to highlight candidate proteins and validated their presence in pooled plasma-generated EVs from 30 healthy controls and 30 CRC patients. From these, we chose 14 potential EV-derived targets for further quantification by targeted MS assay in a separate individual cohort comprising of 73 CRC and 80 healthy subjects. Quantitative analyses revealed significant increases in ADAM10, CD59 and TSPAN9 levels (2.19- to 5.26-fold, p < 0.0001) in plasma EVs from CRC patients, with AUC values of 0.83, 0.95 and 0.87, respectively. Higher EV CD59 levels were significantly correlated with distant metastasis (p = 0.0475), and higher EV TSPAN9 levels were significantly associated with lymph node metastasis (p = 0.0011), distant metastasis at diagnosis (p = 0.0104) and higher TNM stage (p = 0.0065). A two-marker panel consisting of CD59 and TSPAN9 outperformed the conventional marker CEA in discriminating CRC and stage I/II CRC patients from healthy controls, with AUC values of 0.98 and 0.99, respectively. Our results identify EV membrane proteins in common among CRC cell lines and altered plasma EV protein profiles in CRC patients and suggest plasma EV CD59 and TSPAN9 as a novel biomarker panel for detecting early-stage CRC.

According to a study from World Health Organization's Global Burden of Disease, mental and neurological disorders have accounted for 13% of global diseases in recent years and are on the rise. Neuropsychiatric conditions or neuroinflammatory disorders are linked by the presence of an exaggerated immune response both peripherally and in the central nervous system (CNS). Cognitive dysfunction (CD) encompasses a complex group of diseases and has frequently been described in the field of autoimmune diseases, especially in multiple non-CNS-related autoimmune diseases. Recent studies have provided various hypotheses regarding the occurrence of cognitive impairment in autoimmune diseases, including that abnormally activated immune cells can disrupt the integrity of the blood-brain barrier (BBB) to trigger a central neuroinflammatory response. When the BBB is intact, autoantibodies and pro-inflammatory molecules in peripheral circulation can enter the brain to activate microglia, inducing CNS inflammation and CD. However, the mechanisms explaining the association between the immune system and neural function and their contribution to diseases are uncertain. In this review, we used clinical statistics to illustrate the correlation between CD and autoimmune diseases that do not directly affect the CNS, summarized the clinical features and mechanisms by which autoimmune diseases trigger cognitive impairment, and explored existing knowledge regarding the link between CD and autoimmune diseases from the perspective of the field of neuroimmunology., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 The Authors. Publishing Services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Chronic neuropathic pain (CNP) refers to pain that lasts for more than three months due to a disease or an injury to the somatosensory nervous system. The incidence of CNP has been increasing in the world, causing it to become a global concern and patients often experience spontaneous pain, hyperalgesia, abnormal pain or even abnormal sensation as some of its main symptoms. In addition to serious pain and poor physical health, CNP also negatively affects patients' mental health, thus impacting the overall quality of their lives. The pathogenesis of CNP is not clear, but some studies have proved that central sensitization, peripheral sensitization, neuroinflammation, dysfunction in descending nociceptive modulatory systems, oxidative stress reaction, activation of glial cells and psychological factors play an important role in the occurrence and development of CNP. In this context, this article summarizes the current research progress on the mechanism of CNP to provide a basis for further research in preventing and treating the disease., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, author- ship, and/or publication of this article., (© 2022 Published by Elsevier Ltd on behalf of International Brain Research Organization.)

Our study aims to characterize metabolite profiles, varying by major determinants in brewed coffee as follows: three post-harvest processing, three roasting degrees, and two brewing methods for C. arabicacv. Geisha. The major discriminant factor was the roasting degree, explaining 58.84% of the total variance of metabolite profiles. Despite a lesser degree of influence, specific metabolite profiles were retained in temperature-based brewing (Light, 11.11%; Medium, 12.01%; Dark, 22.15%) and post-harvest processing (Light, 35.29%; Medium, 29.64%; Dark, 22.03%), respectively. The effect of pressure application on the coffee metabolome was significant only for the light roasted beans (9.88%). Of note, the post-harvest processing method was featured by norharman (anaerobic), pimelic acid (natural), and xanthine (washed). In addition, our study proposed novel compounds, DiHOMEs, associated with potential health benefits, which will step-up the coffee values and suggest future direction of the development of coffee processing., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: To identify risk factors for hospital-acquired pneumonia (HAP) in patients with aneurysmal subarachnoid hemorrhage (aSAH) and establish a predictive model to aid evaluation., Methods: The cohorts of 253 aSAH patients were divided into the HAP group ( n = 64) and the non-HAP group ( n = 189). Univariate and multivariate logistic regression were performed to identify risk factors. A logistic model (Model-Logit) was established based on the independent risk factors. We used risk factor categories to develop a model (Model-Cat). Receiver operating characteristic curves were generated to determine the cutoff values. Areas under the curves (AUCs) were calculated to assess the accuracy of models and single factors. The Delong test was performed to compare the AUCs., Results: The multivariate logistic analysis showed that the age [ p = 0.012, odds ratio (OR) = 1.059, confidence interval (CI) = 1.013-1.107], blood glucose (BG; >7.22 mmol/L; p = 0.011, OR = 2.781, CI = 1.263-6.119), red blood distribution width standard deviation (RDW-SD; p = 0.024, OR = 1.118, CI = 1.015-1.231), and Glasgow coma scale (GCS; p < 0.001, OR = 0.710, CI = 0.633-0.798) were independent risk factors. The Model-Logit was as follows: Logit( P ) = -5.467 + 0.057 * Age + 1.023 * BG (>7.22 mmol/L, yes = 1, no = 0) + 0.111 * RDW-SD-0.342 * GCS. The AUCs values of the Model-Logit, GCS, age, BG (>7.22 mmol/L), and RDW-SD were 0.865, 0.819, 0.634, 0.698, and 0.625, respectively. For clinical use, the Model-Cat was established. In the Model-Cat, the AUCs for GCS, age, BG, and RDW-SD were 0.850, 0.760, 0.700, 0.641, and 0.564, respectively. The AUCs of the Model-Logit were insignificantly higher than the Model-Cat (Delong test, p = 0.157). The total points from -3 to 4 and 5 to 14 were classified as low- and high-risk levels, respectively., Conclusions: Age, BG (> 7.22 mmol/L), GCS, and RDW-SD were independent risk factors for HAP in aSAH patients. The Model-Cat was convenient for practical evaluation. The aSAH patients with total points from 5 to 14 had a high risk for HAP, suggesting the need for more attention during treatment., 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 Hu, Hu, Chen and Yu.)

Background: Peripheral facial nerve palsy is a general term used to describe diseases that cause lower motor neuron lesions in the facial nerve. The most common cause of peripheral facial nerve palsy is idiopathic Bell's palsy (BP), accounting for 60% to 70% of all peripheral facial nerve palsy cases. Idiopathic BP is found in various medical conditions, such as ischemia, viral infection, and neuroinflammation; however, the specific pathophysiology remains unclear. Neuroimaging techniques help understand the neural mechanisms underlying various neurological disorders. In recent years, several studies have applied functional neuroimaging to investigate alterations of brain function in BP patients. However, the results have been inconsistent due to differences in methodology and quality. Moreover, systematic reviews of studies on functional neuroimaging for BP are insufficient. Therefore, the present study aims to verify the neural mechanisms of brain alterations and draw conclusions about the functional reorganization in patients with BP., Methods: This review includes all suitable studies published on or before October 31, 2022. A thorough search will be conducted using the following databases: MEDLINE, Cochrane Library, Excerpta Medica Database (EMBASE), China Knowledge Resource Integrated Database (CNKI), Korean Medical database (KMBASE), Korean Studies Information Service System (KISS). Clinical studies of BP using functional neuroimaging will be selected. We will apply a coordinate-based meta-analysis because most individual neuroimaging studies provide their results as coordinates in the standard space. The primary outcomes will include the types of functional neuroimaging methods and alterations of brain function in BP patients. The secondary outcomes will include the information about clinical measurement of the disease. Study selection, data extraction, and risk of bias assessment will be conducted. If possible, heterogeneity tests, data synthesis, and subgroup analyses will be conducted., Results: The study will analyze the alterations in brain activity and worsening of clinical symptoms caused by idiopathic BP., Conclusion: The aim of this study is to investigate functional reorganization of brain alterations in patients with BP. This review will improve the understanding of the neural mechanisms of BP based on the most recent publications through extensive data retrieval. If sufficient data are collected, a sensitivity analysis is performed to verify the robustness of the conclusions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To identify the morphologic and hemodynamic risk factor of mirror middle cerebral artery (MCA) aneurysms., Methods: We conducted a retrospective analysis of 40 paired mirror MCA aneurysms. Aneurysms were divided into ruptured and unruptured groups. Seventeen morphological and nine hemodynamic parameters were measured using computer-assisted semiautomated measurement (CASAM) and computer flow dynamic (CFD) simulation. We performed a paired t-test (for normally distributed data) or a paired Wilcoxon rank-sum (for non-normally distributed data) to analyze all parameters between the groups. Multivariate conditional logistic regression analysis identified independent risk factors. The receiver operating characteristic curve was analyzed to acquire the area under the curve (AUC) and the cutoff values of the independent risk factors., Results: There were significant differences in morphological and hemodynamic parameters between the ruptured and unruptured mirror aneurysms. The multivariate logistic analysis showed that the greater size (odds ratio [OR] = 9.807, p = 0.003), smaller neck diameter (OR = 0.285, p = 0.018) and maximum oscillatory shear index (OSI) (OR = 0.000001, p = 0.046) were independently correlated with aneurysm rupture. AUCs for size, N. and maximum OSI were 0.794, 0.695, and 0.701, respectively. The cutoff values of the size, neck diameter, and maximum OSI were 6.30, 5.07, and 0.356437, respectively., Conclusions: Morphology and hemodynamics can help predict aneurysm rupture risks. The more significant size, smaller neck diameter and maximum OSI were independent risk factors for the rupture of MCA aneurysms. The variables could aid practical risk evaluation., Competing Interests: Declaration of Competing Interest 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: A substantial number of randomized controlled trial (RCT) studies in total joint arthroplasty (TJA) are published each year in the United States (US). However, it is unknown how closely the demographic and clinical characteristics of these cohorts resemble that of the US patient population undergoing TJA. Thus, the purpose of this systematic review was to evaluate the patient characteristics of published RCTs in TJA in the US and to compare these characteristics against patient cohorts from national patient databases., Methods: RCT studies regarding primary TJA conducted in the US were selected. Key patient demographics were aggregated and compared against demographics characteristics of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality National Inpatient Sample (NIS) and American College of Surgeons National Surgical Quality Improvement Program patient cohorts., Results: One hundred and fifty-three RCTs fulfilled the inclusion criteria and were included. The total number of patients in the 153 RCTs was 24,135 patients. The average age of patients in the TJA RCT cohort was 65 years (53-80) while the NIS cohort was 67 years (18-90) (d = 0.21, effect size = small). The average body mass index of the TJA RCT cohort was 30.8 (18.2-37.6) while the National Surgical Quality Improvement Program cohort was 31.9 (14.1-59.6) (d = 0.18, effect size = small). For TJA, effect sizes for age, body mass index BMI, sex, ethnicity, smoking, and diabetes were all small or very small., Conclusion: Overall, the US RCT patient cohort for TJA does not differ substantially from the general patient population undergoing TJA in the United States. Differences in demographic and clinical characteristics between the TJA RCT cohort and database cohorts ranged from minimal to small, suggesting that these differences are unlikely to impact clinical outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims/hypothesis: CD40 expressed in Müller cells is a central driver of diabetic retinopathy. CD40 causes phospholipase Cγ1 (PLCγ1)-dependent ATP release in Müller cells followed by purinergic receptor (P2X 7 )-dependent production of proinflammatory cytokines in myeloid cells. In the diabetic retina, CD40 and P2X 7 upregulate a broad range of inflammatory molecules that promote development of diabetic retinopathy. The molecular event downstream of CD40 that activates the PLCγ1-ATP-P2X 7 -proinflammatory cytokine cascade and promotes development of diabetic retinopathy is unknown. We hypothesise that disruption of the CD40-driven molecular events that trigger this cascade prevents/treats diabetic retinopathy in mice., Methods: B6 and transgenic mice with Müller cell-restricted expression of wild-type (WT) CD40 or CD40 with mutations in TNF receptor-associated factor (TRAF) binding sites were made diabetic using streptozotocin. Leucostasis was assessed using FITC-conjugated concanavalin A. Histopathology was examined in the retinal vasculature. Expression of inflammatory molecules and phospho-Tyr783 PLCγ1 (p-PLCγ1) were assessed using real-time PCR, immunoblot and/or immunohistochemistry. Release of ATP and cytokines were measured by ATP bioluminescence and ELISA, respectively., Results: Human Müller cells with CD40 ΔT2,3 (lacks TRAF2,3 binding sites) were unable to phosphorylate PLCγ1 and release ATP in response to CD40 ligation, and could not induce TNF-α/IL-1β secretion in bystander myeloid cells. CD40-TRAF signalling acted via Src to induce PLCγ1 phosphorylation. Diabetic mice in which WT CD40 in Müller cells was replaced by CD40 ΔT2,3 failed to exhibit phosphorylation of PLCγ1 in these cells and upregulate P2X 7 and TNF-α in microglia/macrophages. P2x 7 (also known as P2rx7), Tnf-α (also known as Tnf), Il-1β (also known as Il1b), Nos2, Icam-1 (also known as Icam1) and Ccl2 mRNA were not increased in these mice and the mice did not develop retinal leucostasis and capillary degeneration. Diabetic B6 mice treated intravitreally with a cell-permeable peptide that disrupts CD40-TRAF2,3 signalling did not exhibit either upregulation of P2X 7 and inflammatory molecules in the retina or leucostasis., Conclusions/interpretation: CD40-TRAF2,3 signalling activated the CD40-PLCγ1-ATP-P2X 7 -proinflammatory cytokine pathway. Src functioned as a link between CD40-TRAF2,3 and PLCγ1. Replacing WT CD40 with CD40 ΔT2,3 impaired activation of PLCγ1 in Müller cells, upregulation of P2X 7 in microglia/macrophages, upregulation of a broad range of inflammatory molecules in the diabetic retina and the development of diabetic retinopathy. Administration of a peptide that disrupts CD40-TRAF2,3 signalling reduced retinal expression of inflammatory molecules and reduced leucostasis in diabetic mice, supporting the therapeutic potential of pharmacological inhibition of CD40-TRAF2,3 in diabetic retinopathy., (© 2022. The Author(s).)

An unprecedented tandem trifluoromethylsilylation/intramolecular S N 2 substitution sequence was realized by using bifunctional reagent Me 2 (CH 2 Cl)SiCF 3 , allowing efficient construction of valuable trifluoromethylated oxasilacyclohexanes that are difficult to access by known methods. Initial attempts into developing asymmetric variant reveal that using cinchonine-derived dimeric PTC catalyst could afford chiral oxasilacyclohexanes in up to 92% enantiomeric excess.

Snakebites from Protobothrops mucrosquamatus (Taiwan habus) and Viridovipera stejnegeri (green bamboo vipers) account for the most venomous snakebites in Taiwan. The bivalent freeze-dried hemorrhagic (FH) antivenom is employed to treat these two snakebite patients without a strict clinical trial. We evaluated the clinical usefulness of Taiwan bivalent freeze-dried hemorrhagic (FH) antivenom in Taiwan habu- and green bamboo viper-envenomed patients. We checked ELISA- based serum venom antigen levels before and after FH antivenom to evaluate FH's ability to neutralize patients' serum snake venom and its usefulness in reducing limb swelling after snakebites. Patients who had higher serum venom antigen levels had more severe limb swelling. Of the 33 enrolled patients, most of their snake venom antigen levels were undetected after the appliance of antivenom. Most enrolled patients (25/33) had their limb swelling subside within 12 h after antivenom treatment. The failure to reduce limb swelling was probably due to an inadequate antivenom dose applied in more severely envenomated patients. Our data indicate the feasibility of the FH antivenom in effectively eliminating venom and resolving the affected limb swelling caused by Taiwan habu and green bamboo viper bites.

Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children in the USA. Sixteen percent of hemispheric pediatric and young adult HGGs encode Gly34Arg/Val substitutions in the histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy and therapeutic resistance in pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) and human pHGG cells encoding H3.3-G34R, we demonstrate that this mutation led to the downregulation of DNA repair pathways. This resulted in enhanced susceptibility to DNA damage and inhibition of the DNA damage response (DDR). We demonstrate that genetic instability resulting from improper DNA repair in G34R-mutant pHGG led to the accumulation of extrachromosomal DNA, which activated the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway, inducing the release of immune-stimulatory cytokines. We treated H3.3-G34R pHGG-bearing mice with a combination of radiotherapy (RT) and DNA damage response inhibitors (DDRi) (i.e., the blood-brain barrier-permeable PARP inhibitor pamiparib and the cell-cycle checkpoint CHK1/2 inhibitor AZD7762), and these combinations resulted in long-term survival for approximately 50% of the mice. Moreover, the addition of a STING agonist (diABZl) enhanced the therapeutic efficacy of these treatments. Long-term survivors developed immunological memory, preventing pHGG growth upon rechallenge. These results demonstrate that DDRi and STING agonists in combination with RT induced immune-mediated therapeutic efficacy in G34-mutant pHGG.

Using a sample of (10.09±0.04)×10^{9}  J/ψ events collected with the BESIII detector operating at the BEPCII storage ring, a partial wave analysis of the decay J/ψ→γηη^{'} is performed. The first observation of an isoscalar state with exotic quantum numbers J^{PC}=1^{-+}, denoted as η&#95;{1}(1855), is reported in the process J/ψ→γη&#95;{1}(1855) with η&#95;{1}(1855)→ηη^{'}. Its mass and width are measured to be (1855±9&#95;{-1}^{+6})  MeV/c^{2} and (188±18&#95;{-8}^{+3})  MeV, respectively, where the first uncertainties are statistical and the second are systematic, and its statistical significance is estimated to be larger than 19σ.

Osteoporosis constitutes a significant public health risk. An estimated 10.2 million adults in the United States >50 years of age have osteoporosis, a systemic condition that weakens the bones increasing the susceptibility for fractures. Approximately one-half of women and nearly one-third of men >50 years of age will sustain an osteoporotic fracture. These fractures are associated with a decrease in quality of life, diminished physical function, and reduced independence. Dual-energy X-ray absorptiometry (DXA) is the primary imaging modality used to screen for osteoporosis in women >65 years of age and men >70 years of age. DXA may be used in patients <65 years of age to evaluate bone mass density if there are additional risk factors. In certain situations, vertebral fracture assessment and trabecular bone score may further predict fracture risk, particularly in patients who are not yet osteoporotic but are in the range of osteopenia. Quantitative CT is useful in patients with advanced degenerative changes in the spine. Given the proven efficacy of pharmacologic therapy, the role of imaging to appropriately identify and monitor high-risk individuals is critical in substantially reducing osteoporosis-associated morbidity and mortality, and reducing the considerable cost to the health care system. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

A highly enantio- and regio-selective Markovnikov hydromonofluoro(methyl)alkylation of 1,3-dienes was developed using redox-neutral nickel catalysis. It provided a facile strategy to construct diverse monofluoromethyl- or monofluoroalkyl-containing chiral allylic molecules. Notably, this represents the first catalytic asymmetric Markovnikov hydrofluoroalkylation of olefins. The practicability of this methodology is further highlighted by its broad substrate scope, mild base-free conditions, excellent enantio- and regio-selectivity, and diversified product elaborations to access useful fluorinated building blocks., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: In addition to established prognostic factors in low-grade glioma (LGG), studies suggest a sexual dimorphism with male sex portending worse prognosis. Our objective was to identify the effect of sex on presentation and outcomes in LGG., Methods and Materials: We conducted a retrospective cohort study of adults (aged ≥18 years) diagnosed with LGG (World Health Organization 2016 grade 2 glioma). Patients with IDH wild-type tumors were excluded. Patients were matched between male and female sex by age, treatment, and surgery via propensity score matching. Patient, tumor, and treatment characteristics were analyzed by sex. Endpoints included overall survival (OS), next intervention-free survival (NIFS), progression-free survival, and malignant transformation-free survival. Kaplan-Meier analyses and Cox proportional hazards regression multivariable analysis with backward elimination were completed., Results: Of the 532 patients identified, 258 (48%) were men. Men were more likely to present with seizure (69.38% vs 56.57%, P = .002), but no other statistically significant differences between sexes at presentation were identified. Five-year OS was higher in women at 87% (95% confidence interval [CI], 83%-91%) versus 78% (95% CI, 73%-84%) in men (P = .0045). NIFS was significantly higher in female patients at 68% (95% CI, 62%-74%) versus 57% (95% CI, 51%-64%) in men (P = .009). On multivariable analysis, female sex was independently associated with improved OS (hazard ratio [HR], 1.54; 95% CI, 1.16-2.05; P = .002), NIFS (HR, 1.42; 95% CI, 1.42; P = .004), and malignant transformation-free survival (HR, 1.62; 95% CI, 1.24-2.12; P = .0004). In patients with molecularly defined LGG (IDH and 1p19q status; n = 291), female sex remained independently associated with improved OS (HR, 1.79; 95% CI, 1.16-2.77; P = .008) and NIFS (HR, 1.45; 95% CI, 1.07-1.96; P = .016)., Conclusions: In this study, female sex was independently associated with improved outcomes. These findings support intrinsic sex-specific differences in LGG behavior, justifying further studies to optimize management and therapeutics based on sex., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this article is to evaluate effects of self-determination theory-based on-campus and off-campus prevention programs on smartphone overdependence among university students., Methods: This was a pre-posttest quasi-experimental study with a nonequivalent control group (CG). Seventy-eight students were recruited as participants. They were allowed to choose either an experiment group (EG) or a CG. On-campus smartphone overdependence prevention program was provided to participants in experimental group 1 (EG1), while on-campus program combined with off-campus prevention camp was provided to those in experimental group 2 (EG2). Instruments used in this study included a smartphone overdependence self-diagnosis scale, a basic psychological needs scale, and a self-regulation ability scale. Data collection was performed at baseline, immediately after intervention, at 1 month and 3 months after intervention. Data were analyzed using mixed analysis of covariance. Focus group interview was performed for qualitative evaluation., Results: After the intervention, smartphone overdependence and basic psychological needs exhibited significant interactions between group and time. Smartphone overdependence scores decreased in EG1 and EG2 but increased in CG (F = 4.56, p = .001). Basic psychological needs improved in EG1 and EG2 but deteriorated in CG (F = 5.04, p = .009). Focus group interviews revealed that participants strived to control their smartphone usage through individual efforts and by interacting with new friends in college even after completing the program., Conclusion: In this study, on-campus only program and combined intervention of on- and off-campus programs were both effective in maintaining and managing smartphone use. However, participants perceived that the off-campus program provided an opportunity to apply the theory learned in on-campus to the real world., (Copyright © 2022. Published by Elsevier B.V.)

Deciphering the crosstalk between RNA-binding proteins and corresponding RNAs will provide a better understanding of gastric cancer (GC) progression. The comprehensive bioinformatics study identified cytoplasmic polyadenylation element-binding protein 3 (CPEB3) might play a vital role in GC progression. Then we found CPEB3 was downregulated in GC and correlated with prognosis. In addition, CPEB3 suppressed GC cell proliferation, invasion and migration in vitro, as well as tumor growth and metastasis in vivo. Mechanistic study demonstrated CPEB3 interacted with 3'-UTR of ADAR1 mRNA through binding to CPEC nucleotide element, and then inhibited its translation by localizing it to processing bodies (P bodies), eventually leading to the suppression of ADAR1-mediated RNA editing. Microscale thermophoresis assay further revealed that the direct interaction between CPEB3 and GW182, the P-body's major component, was through the 440-698AA region of CPEB3 binding to the 403-860AA region of GW182. Finally, AAV9-CPEB3 was developed and administrated in mouse models to assess its potential value in gene therapy. We found AAV9-CPEB3 inhibited GC growth and metastasis. Besides, AAV9-CPEB3 induced hydropic degeneration in mouse liver, but did not cause kidney damage. These findings concluded that CPEB3 suppresses GC progression by inhibiting ADAR1-mediated RNA editing via localizing ADAR1 mRNA to P bodies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Metastasis is a leading cause of cancer-related deaths. Hence, the discovery of more reliable metastasis-related biomarkers is crucial to improve the survival rate of cancer patients. W3 is an aptamer previously produced by the subtractive cell-SELEX using metastatic colorectal cancer cells as target cells and non-metastatic cells as negative cells. In this study, we aimed to evaluate whether the target molecule of W3 can potentially act as a metastatic biomarker. First, we obtained two cell subpopulations with different expression levels of the target molecule by W3-based cell sorting. Subsequently, we demonstrated that W3 high cells have a higher metastatic potential than W3 low cells both in vitro and in vivo. Further, immunohistochemical analysis revealed that W3 target expression is positively associated with metastasis and poor prognosis of CRC patients. Using mass spectrometry (MS) combined with pull-down, we identified that Ephrin type-A receptor 2 (EphA2) is the target of W3. EphA2's potential as a metastatic predictor was demonstrated by capturing W3-positive circulating tumor cells from CRC patients using a W3 probe. Based on these results, we put forward a stratagem for cell-SELEX-based biomarker discovery: selecting an aptamer through subtractive cell-SELEX towards the phenotype of interest; evaluating the functional phenotype of the target molecule by aptamer-based target cell sorting and analysis of clinical samples; and identifying the aptamer's target molecule using MS and aptamer-based target enrichment. This stratagem not only shortens the time for the clinical application of aptamers but also enables a more targeted and efficient discovery of biomarkers., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The molecular pathogenesis of malignant gliomas, characterized by diverse tumor histology with differential prognosis, remains largely unelucidated. An APOBEC3 deletion polymorphism, with a deletion in APOBEC3B, has been correlated to risk and prognosis in several cancers, but its role in glioma is unclear. The authors aimed to examine the clinical relevance of the APOBEC3 deletion polymorphism to glioma risk and survival in a glioma patient cohort in Taiwan., Methods: The authors detected deletion genotypes in 403 glioma patients and 1365 healthy individuals in Taiwan and correlated the genotypes with glioma risk, clinicopathological factors, patient survival, and patient sex. APOBEC3 gene family expression was measured and correlated to the germline deletion. A nomogram model was constructed to predict patient survival in glioma., Results: The proportion of APOBEC3B-/- and APOBEC3B+/- genotypes was higher in glioblastoma (GBM) patients than healthy individuals and correlated with higher GBM risk in males. A higher percentage of cases with APOBEC3B- was observed in male than female glioma patients. The presence of APOBEC3B-/- was correlated with better overall survival (OS) in male astrocytic glioma patients. No significant correlation of the genotypes to glioma risk and survival was observed in the female patient cohort. Lower APOBEC3B expression was observed in astrocytic glioma patients with APOBEC3B-/- and was positively correlated with better OS. A 5-factor nomogram model was constructed based on male patients with astrocytic gliomas in the study cohort and worked efficiently for predicting patient OS., Conclusions: The germline APOBEC3 deletion was associated with increased GBM risk and better OS in astrocytic glioma patients in the Taiwan male population. The APOBEC3B deletion homozygote was a potential independent prognostic factor predicting better survival in male astrocytic glioma patients.

Inspired by the desire to solve the energy-related issues in remote sensing applications, internet of things, wireless autonomous devices, and self-powered portable electronic devices, triboelectric nanogenerators (TENGs) have been highly promoted. However, for use in the specified applications, especially in wearable and biomedical devices, environmental-friendly materials are required. Herein, an eco-friendly pectin polymer is used as a positive triboelectric material to fabricate a TENG with excellent output performance. Working in conjunction with a polyimide, the polyimide and microarchitected pectin (MA@pectin) polymer film-based TENG (PP-TENG) generated open circuit voltage ( V OC ), short circuit current ( I SC ), and charge density ( Q SC ) of ∼300 V, 14 μA, and 70 μC cm -2 , respectively, exhibiting remarkable enhancement compared to the TENG based on polyimide/pristine pectin polymer ( V OC , I SC , and Q SC of 170 V, 7.6 μA, and 47 μC cm -2 , respectively) under similar operating conditions. The output performance of the PP-TENG is particularly reliant on the pectin concentration, indicating an optimum concentration of 9 wt%. The improved performance of the PP-TENG was systematically analyzed and explained in terms of pectin concentration, dielectric constant, and surface roughness. Furthermore, the PP-TENG can power portable electronic devices and light-emitting diodes to prove the capability of the TENG in practical applications. The fabricated PP-TENG is anticipated to be a sustainable energy harvester via a low-cost and facile approach.

Objectives: This study aims to identify the effectiveness of the clip-reinforced wrapping using the Y-shaped temporalis fascia (CRYST) technique for treating intracranial aneurysms (IAs)., Methods: We retrospectively reviewed five patients with ruptured IAs treated using the CRYST technique from July 2016 to May 2021. Three patients had blood blister-like aneurysms (BBAs) (one with intraoperative rupture), and two had anterior communicating artery (AcoA) aneurysms (one with intraoperative rupture). All patients had intraoperative indocyanine green angiography, and digital subtraction angiography (DSA) was reviewed 10-14 days after surgery. At 1 year postoperatively, three patients (two BBAs and one AcoA aneurysm) underwent DSA and two patients (one BBA and one AcoA aneurysm) underwent computed tomographic angiography (CTA)., Results: Two aneurysms ruptured intraoperatively during the clipping, and no severe complications occurred. No patients had neurological deficits after surgery, and they had good outcomes. Four DSAs showed no aneurysms and no significant stenosis of the parent artery 10-14 days after surgery. One patient had mild stenosis of the parent artery on DSA 10 days after surgery; the stenosis improved on DSA 1 year after surgery. No other aneurysms recurred, and parent arteries were clear on CTA or DSA 1 year after surgery., Conclusions: Combining our accumulated experience in the work and literature, we described the CRYST technique to treat intractable IAs with specific morphologies and irregular wall structures in our patients. All outcomes and follow-up results were favorable., 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., (© 2022 Hu, Chen, Xu and Yu.)

We report the development of bifunctional trifluoromethylsilyl reagents for selective trifluoromethylation. The newly developed reagent, Me 2 (CH 2 Cl)SiCF 3 , allows highly enantioselective trifluoromethylations of ketones with broad scope. Notably, by taking advantage of the chloromethyl group, a tandem synthesis of chiral trifluoromethylated oxasilacyclopentanes is developed, paving way to α-CF 3 tertiary alcohols with vicinal tertiary or quaternary stereocenters. Theoretical studies revealed the important role of nonclassical C-H⋅⋅⋅F-C interactions in stabilizing the transition state, and that the presence of the chlorine atom enhances such interactions for better enantiofacial control., (© 2022 Wiley-VCH GmbH.)

Objective: Glioblastoma has been known to be resistant to chemotherapy and radiation, whereas the underlying mechanisms of resistance have not been fully elucidated. The authors studied the role of the transcription factor ZEB1 (zinc finger E-box-binding homeobox 1 protein), which is associated with epithelial-mesenchymal transition (EMT) and is central to the stemness of glioblastoma, to determine its role in therapeutic resistance to radiation and chemotherapy. The authors previously demonstrated that ZEB1 is deleted in a majority of glioblastomas., Methods: The authors explored resistance to therapy in the context of ZEB1 loss and overexpression in glioma stem cells (GSCs) and in patient data., Results: Patients with ZEB1 loss had a shorter survival time than patients with wild-type ZEB1 in both the high- and low-MGMT groups. Consistent with the clinical data, mice implanted with ZEB1 knockdown GSCs showed shortened survival compared with mice inoculated with nonsilencing control (NS) short-hairpin RNA (shRNA) GSC glioblastoma. ZEB1-deleted GSCs demonstrated increased tumorigenicity with regard to proliferation and invasion. Importantly, GSCs that lose ZEB1 expression develop enhanced resistance to chemotherapy, radiotherapy, and combined chemoradiation. ZEB1 loss may lead to increased HER3 expression through the HER3/Akt pathway associated with this chemoresistance. Conversely, overexpression of ZEB1 in GSCs that are ZEB1 null leads to increased sensitivity to chemoradiation., Conclusions: The study results indicate that ZEB1 loss in cancer stem cells confers resistance to chemoradiation and uncovers a potentially targetable cell surface receptor in these resistant cells.

We study the direct production of the J^{PC}=1^{++} charmonium state χ&#95;{c1}(1P) in electron-positron annihilation by carrying out an energy scan around the mass of the χ&#95;{c1}(1P). The data were collected with the BESIII detector at the BEPCII collider. An interference pattern between the signal process e^{+}e^{-}→χ&#95;{c1}(1P)→γJ/ψ→γμ^{+}μ^{-} and the background processes e^{+}e^{-}→γ&#95;{ISR}J/ψ→γ&#95;{ISR}μ^{+}μ^{-} and e^{+}e^{-}→γ&#95;{ISR}μ^{+}μ^{-} is observed by combining all the data samples. The χ&#95;{c1}(1P) signal is observed with a significance of 5.1σ. This is the first observation of a C-even state directly produced in e^{+}e^{-} annihilation. The electronic width of the χ&#95;{c1}(1P) resonance is determined to be Γ&#95;{ee}=(0.12&#95;{-0.08}^{+0.13})  eV, which is of the same order of magnitude as theoretical calculations.

Despite therapeutic interventions for glioblastoma (GBM), cancer stem cells (CSCs) drive recurrence. The precise mechanisms underlying CSC resistance, namely inhibition of cell death, are unclear. We built on previous observations that the high cell surface expression of junctional adhesion molecule-A drives CSC maintenance and identified downstream signaling networks, including the cysteine protease inhibitor SerpinB3. Using genetic depletion approaches, we found that SerpinB3 is necessary for CSC maintenance, survival, and tumor growth, as well as CSC pathway activation. Knockdown of SerpinB3 also increased apoptosis and susceptibility to radiation therapy. SerpinB3 was essential to buffer cathepsin L-mediated cell death, which was enhanced with radiation. Finally, we found that SerpinB3 knockdown increased the efficacy of radiation in pre-clinical models. Taken together, our findings identify a GBM CSC-specific survival mechanism involving a cysteine protease inhibitor, SerpinB3, and provide a potential target to improve the efficacy of GBM therapies against therapeutically resistant CSCs., Competing Interests: Declaration of interests M.S.A. is the recipient of grants/research support from AstraZeneca, Abbvie, Bristol Myers Squibb, Bayer, Incyte, Pharmacyclics, Novocure, and Merck; is a shareholder in Doctible and Mimivax; and has received honoraria or consultation fees from Wiley, Abvvie, Bayer, Elsevier, Forma Therapeutics, Karyopharm Therapeutics, Tocagen, and VBI Vaccines. The remaining authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To identify hemodynamic risk factors for intracranial aneurysm rupture and establish a predictive model to aid evaluation., Methods: We analyzed the hemodynamic parameters of 91 pairs of ruptured mirror aneurysms. A conditional univariate analysis was used for the continuous variables. A conditional multivariate logistic regression analysis was performed to identify the independent risk factors. Differences where p < 0.05 were statistically significant. A predictive model was established based on independent risk factors. Odds ratios (ORs) were used to score points. The validation cohort consisted of 189 aneurysms. Receiver operating characteristic curves were generated to determine the cutoff values and area under the curves (AUCs) of the predictive model and independent risk factors., Results: The conditional multivariate logistic analysis showed that the low shear area (LSA) (OR = 70.322, p = 0.044, CI = 1.112-4,445.256), mean combined hemodynamic parameter (CHP) (>0.087) (OR = 3.171, p = 0.034, CI = 1.089-9.236), and wall shear stress gradient (WSSG) ratio (>893.180) (OR = 5.740, p = 0.003, CI = 1.950-16.898) were independent risk factors. A prediction model was established: 23 * LSA + 1 * CHP mean (>0.087: yes = 1, no = 0) + 2 * WSSG ratio (>893.180: yes = 1, no = 0). The AUC values of the predictive model, LSA, mean CHP (>0.087), and WSSG ratio (>893.180) were 0.748, 0.700, 0.654, and 0.703, respectively. The predictive model and LSA cutoff values were 1.283 and 0.016, respectively. In the validation cohort, the predictive model, LSA, CHP (>0.087), and WSSG ratio (>893.180) were 0.736, 0.702, 0.689, and 0.706, respectively., Conclusions: LSA, CHP (>0.087), and WSSG ratio (>893.180) were independent risk factors for aneurysm rupture. Our predictive model could aid practical evaluation., 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 Hu, Chen, Xu, Li and Yu.)

Hepatocellular carcinoma (HCC) is the fastest-growing tumor capable of spreading to other organs via blood vessels formed by endothelial cells. Apoptosis and angiogenesis-targeting therapies are attractive for cancer treatment. In this study, we aimed to study the in vitro cytotoxicity of Withania somnifera against human HCC (HepG2) cells, identify potential antitumoral withanolide glycosides from the active fraction, and elucidate cytotoxic molecular mechanisms of identified bioactive compounds. W. somnifera (Solanaceae), well-known as 'ashwagandha', is an Ayurvedic medicinal plant used to promote health and longevity, and the MeOH extract of W. somnifera root exhibited cytotoxicity against HepG2 cells during initial screening. Bioactivity-guided fractionation of the MeOH extract and subsequent phytochemical investigation of the active n -BuOH-soluble fraction resulted in the isolation of five withanolide glycosides ( 1 - 5 ), including one new metabolite, withanoside XIII ( 1 ), aided by liquid chromatography-mass spectrometry-based analysis. The new compound structure was determined by 1D and 2D nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectroscopy, electronic circular dichroism, and enzymatic hydrolysis. In addition, withanoside XIIIa ( 1a ) was identified as the new aglycone ( 1a ) of 1 . Isolated withanolide glycosides 1-5 and 1a were cytotoxic toward HepG2 cells; withagenin A diglucoside (WAD) ( 3 ) exhibited the most potent cytotoxicity against HepG2 cells, with cell viability less than 50% at 100 μM. WAD cytotoxicity was mediated by both extrinsic and intrinsic apoptosis pathways. Treatment with WAD increased protein expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, Bcl-2-associated X protein (Bax), and cleaved poly(ADP-ribose) polymerase (cleaved PARP) but decreased expression levels of B-cell lymphoma 2 (Bcl-2). Moreover, WAD inhibited tubular structure formation in human umbilical vein endothelial cells (HUVECs) by inhibiting the protein expression of vascular endothelial growth factor receptor 2 and its downstream pathways, including extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR). These effects were also enhanced by co-treatment with ERK and PI3K inhibitors. Overall, these results indicate that WAD ( 3 ) induced HepG2 apoptosis and inhibited HUVEC tube formation, suggesting its potential application in treating liver cancers., Competing Interests: The authors declare that they have no conflict of interest.

Monochamus alternatus is a major forest pest that spreads pine wilt disease in pine trees as a vector of pine wilt nematodes. Chemical insecticides used as fumigants to control overwintering M. alternatus in forests are highly toxic to the environment, so we investigated entomopathogenic fungus Beauveria bassiana ERL836 as an eco-friendly and alternative material to control overwintering M. alternatus. In this work, we evaluated the insecticidal activity of B. bassiana ERL836 against M. alternatus adults, the possibility of fungal colonization on pine tree bark, and finally the control efficacy of fungal pre-treatment on pine tree logs against emerging M. alternatus adults in semi-field and field conditions. M. alternatus adults were killed on the pine tree logs pre-treated with the B. bassiana ERL836. White conidia were observed not only on the surface of the dead adults but also on the pine tree logs, suggesting that the adults were killed by the fungus on the pine. A formulated ERL836 powder treatment on larvae-infested pine logs showed high insecticidal activity against adults, similar to that with the fungal powder suspension treatment, but we demonstrated that using the fungal powder was simpler than using the suspension in field conditions. Even in the field condition, the fungal powder treatment showed high insecticidal activity against M. alternatus adults, which we attribute to its ability to maintain fungal activity for a long time in field conditions by covering the pine tree logs with a film during overwintering. We confirmed that the risk that fungus-infected M. alternatus adults would spread the fungus to other non-target forest insects was low. Thus, even a high-concentration treatment in a specific area is unlikely to transmit the fungus outside that area, so it can be safely used to control this pine wilt nematode vector in forest ecosystems., Competing Interests: The authors have declared that no competing interests exist.

Using a data sample corresponding to an integrated luminosity of 11.3  fb^{-1} collected at center-of-mass energies from 4.23 to 4.70 GeV with the BESIII detector, we measure the product of the e^{+}e^{-}→π^{+}π^{-}ψ&#95;{2}(3823) cross section and the branching fraction B[ψ&#95;{2}(3823)→γχ&#95;{c1}]. For the first time, resonance structure is observed in the cross section line shape of e^{+}e^{-}→π^{+}π^{-}ψ&#95;{2}(3823) with significances exceeding 5σ. A fit to data with two coherent Breit-Wigner resonances modeling the sqrt[s]-dependent cross section yields M(R&#95;{1})=4406.9±17.2±4.5  MeV/c^{2}, Γ(R&#95;{1})=128.1±37.2±2.3  MeV, and M(R&#95;{2})=4647.9±8.6±0.8  MeV/c^{2}, Γ(R&#95;{2})=33.1±18.6±4.1  MeV. Though weakly disfavored by the data, a single resonance with M(R)=4417.5±26.2±3.5  MeV/c^{2}, Γ(R)=245±48±13  MeV is also possible to interpret data. This observation deepens our understanding of the nature of the vector charmoniumlike states. The mass of the ψ&#95;{2}(3823) state is measured as (3823.12±0.43±0.13)  MeV/c^{2}, which is the most precise measurement to date.

Phosphatidylinositol (PI) 4,5-bisphosphate (PIP2) is involved in many biological functions. However, the mechanisms of PIP2 in collective cell migration remain elusive. This study highlights the regulatory role of cytidine triphosphate synthase (CTPsyn) in collective border cell migration through regulating the asymmetrical distribution of PIP2. We demonstrated that border cell clusters containing mutant CTPsyn cells suppressed migration. CTPsyn was co-enriched with Actin at the leading edge of the Drosophila border cell cluster where PIP2 was enriched, and this enrichment depended on the CTPsyn activity. Genetic interactions of border cell migration were found between CTPsyn mutant and genes in PI biosynthesis. The CTPsyn reduction resulted in loss of the asymmetric activity of endocytosis recycling. Also, genetic interactions were revealed between components of the exocyst complex and CTPsyn mutant, indicating that CTPsyn activity regulates the PIP2-related asymmetrical exocytosis activity. Furthermore, CTPsyn activity is essential for RTK-polarized distribution in the border cell cluster. We propose a model in which CTPsyn activity is required for the asymmetrical generation of PIP2 to enrich RTK signaling through endocytic recycling in collective cell migration., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Lithium-sulfur batteries have theoretical specific energy higher than state-of-the-art lithium-ion batteries. However, from a practical perspective, these batteries exhibit poor cycle life and low energy content owing to the polysulfides shuttling during cycling. To tackle these issues, researchers proposed the use of redox-inactive protective layers between the sulfur-containing cathode and lithium metal anode. However, these interlayers provide additional weight to the cell, thus, decreasing the practical specific energy. Here, we report the development and testing of redox-active interlayers consisting of sulfur-impregnated polar ordered mesoporous silica. Differently from redox-inactive interlayers, these redox-active interlayers enable the electrochemical reactivation of the soluble polysulfides, protect the lithium metal electrode from detrimental reactions via silica-polysulfide polar-polar interactions and increase the cell capacity. Indeed, when tested in a non-aqueous Li-S coin cell configuration, the use of the interlayer enables an initial discharge capacity of about 8.5 mAh cm -2 (for a total sulfur mass loading of 10 mg cm -2 ) and a discharge capacity retention of about 64 % after 700 cycles at 335 mA g -1 and 25 °C., (© 2022. UChicago Argonne, LLC, Operator of Argonne National Laboratory.)

Objective: The aim of this study was to explore the correlation between the mean of 24-h venous blood glucose (BG) and in-hospital mortality and all-cause mortality (ACM) in patients with subarachnoid hemorrhage (SAH)., Methods: Detailed clinical information was acquired from the Medical Information Mart for Intensive IV (MIMIC-IV) database. The best cutoff value of mean BG was calculated using the X-tile program. Univariate and multivariate logistic regressive analyses were utilized to analyze the prognosis significance of mean BG, and survival curves were drawn using the Kaplan-Meier (K-M) approach. To improve the reliability of results and balance the impact of underlying confounders, the 1:1 propensity score matching (PSM) approach was utilized., Results: An overall of 1,230 subjects were selected herein. The optimal cutoff value of the mean BG for in-hospital mortality was 152.25. In addition, 367 pairs of score-matched subjects were acquired after PSM analysis, and nearly all variables' differences were balanced. K-M analysis showed that patients with mean BG ≥ 152.25 mg/dl had significantly higher in-hospital, 3-month, and 6-month mortalities compared with patients with mean BG < 152.25 mg/dl ( p < 0.001). The multivariable logistic regressive analyses revealed that patients with mean BG ≥ 152.25 mg/dl had significantly increased in-hospital mortality compared with patients with mean BG < 152.25 mg/dl after the adjustment for possible confounders (OR = 1.994, 95% CI: 1.321-3.012, p = 0.001). Similar outcomes were discovered in the PSM cohort., Conclusion: Our data suggested that mean BG was related to ACM of patients with SAH. More studies are needed to further analyze the role of the mean of 24-h venous BG in patients with SAH., (Copyright © 2022 Wang, Li, Yang, Chen and Yu.)

Purpose: Molecular composition of circulating small extracellular vesicles (EVs) does not merely reflect the cells of origin, but also is enriched in specific biomolecules directly associated with the cellular transformation. However, while most of the currently identified EV-miRs are only geared towards one-dimensional disease detection, their application for long-term tracking and treatment response monitoring has been largely elusive., Methods: We established and optimized a rapid, sensitive and robust liquid biopsy sampling method, and further used small RNA sequencing to comprehensively catalogue EV-miRomes in association with the progression and outcome of metastatic colorectal cancer (mCRC)., Results: By cross-comparison of EV-miRomes (n = 290) from multi-stage and longitudinal cohorts, we uncovered a 15-EV-miR signature with dual detection and long-term monitoring of tumor size progression for mCRC. From this panel, EV-miR-320c was uncovered as a strong clinical marker - aside from its diagnostic power and a therapeutic monitoring performance superior to carcinoembryonic antigen (CEA), its high expression has also been linked to lower overall survival and a greater likelihood of disease recurrence. Further, integrative analyses of tissue transcriptomic and liquid biopsy implicated this 15-EV-miR signature in programming the mesenchymal-epithelial transition (MET) for distant localization of the metastasized cells and also in creating a tumor-favoring metastatic niche., Conclusion: Our clinically-oriented delineation of the mCRC-associated circulating EV-miRomes systematically revealed the functional significance of these liquid biopsy markers and further strengthen their translational potential in mCRC therapeutic monitoring., (© 2022. The Author(s).)

Early diagnosis of metastatic colorectal cancer (mCRC) is extremely critical to improve treatment and extend survival. W3 is an aptamer that can specifically bind to mCRC cells with high affinity. Graphene oxide (GO) is a two-dimensional graphitic carbon nanomaterial, which has widely used in constructing biosensors. In this study, we have developed a no-wash fluorescent aptasensor for one-step and sensitive detection of mCRC LoVo cells. It is based on fluorescence resonance energy transfer (FRET) between GO and the W3 aptamer labeled with 5-carboxyfluorescein (FAM). GO can quench the green fluorescence of the FAM-labeled W3 (FAM-W3). In the presence of the target cells, FAM-W3 preferentially binds the target cells and detaches from the surface of GO, leading to the fluorescence of FAM recovery. It was demonstrated that the fluorescence recovery increases linearly in a wide range of 0~10 7 cells/mL (R 2 = 0.99). The GO-based FAM-labeled W3 aptasensor (denoted as FAM-W3-GO) not only specifically recognizes mCRC cell lines (LoVo and HCT116), but also sensitively differentiates the target cells from mixed cells, even in the presence of only 5% of the target cells. Furthermore, FAM-W3-GO was applied to detect LoVo cells in human whole blood, which showed good reproducibility with an RSD range of 1.49% to 1.80%. Therefore, FAM-W3-GO may have great potential for early diagnosis of mCRC. This strategy of GO-based fluorescent aptasensor provides a simple, one-step, and highly sensitive approach for the detection of mCRC cells.

Based on (10087±44)×10^{6}  J/ψ events collected with the BESIII detector, the process J/ψ→γπ^{+}π^{-}η^{'} is studied using two largest decay channels of the η^{'} meson, η^{'}→γπ^{+}π^{-} and η^{'}→ηπ^{+}π^{-}, η→γγ. A new resonance, which we denote as the X(2600), is observed with a statistical significance larger than 20σ in the π^{+}π^{-}η^{'} invariant mass spectrum, and it has a connection to a structure around 1.5  GeV/c^{2} in the π^{+}π^{-} invariant mass spectrum. A simultaneous fit on the π^{+}π^{-}η^{'} and π^{+}π^{-} invariant mass spectra with the two η^{'} decay modes indicates that the mass and width of the X(2600) state are 2618.3±2.0&#95;{-1.4}^{+16.3}  MeV/c^{2} and 195±5&#95;{-17}^{+26}  MeV, where the first uncertainties are statistical, and the second systematic.

Recent findings have implicated long noncoding RNAs (lncRNAs) as pivotal gene regulators for diverse biological processes, despite their lack of protein-coding capabilities. Accumulating evidence suggests the significance of lncRNAs in mediating cell signaling pathways, especially those associated with tumorigenesis. Consequently, lncRNAs have emerged as novel functional regulators and indicators of cancer development and malignancy. Recent transcriptomic profiling has recognized a tumor-biased expressed lncRNA, the HOXA10-AS transcript, whose expression is associated with patient survival. Functional cell-based assays show that the HOXA10-AS transcript is essential in the regulation of oral cancer growth and metastasis. LncRNA expression is also associated with drug sensitivity. In this study, we identify that HOXA10-AS serves as a modular scaffold for TP63 mRNA processing and that such involvement regulates cancer growth. These findings provide a functional interpretation of lncRNA-mediated molecular regulation, highlighting the significance of the lncRNA transcriptome in cancer biology., (© 2022. The Author(s).)

Chimeric antigen receptor (CAR) T-cell therapy shows promise for treating liquid cancers and increasingly for solid tumors as well. While potential design strategies exist to address translational challenges, including the lack of unique tumor antigens and the presence of an immunosuppressive tumor microenvironment, testing all possible design choices in vitro and in vivo is prohibitively expensive, time consuming, and laborious. To address this gap, we extended the modeling framework ARCADE (Agent-based Representation of Cells And Dynamic Environments) to include CAR T-cell agents (CAR T-cell ARCADE, or CARCADE). We conducted in silico experiments to investigate how clinically relevant design choices and inherent tumor features-CAR T-cell dose, CD4 + :CD8 + CAR T-cell ratio, CAR-antigen affinity, cancer and healthy cell antigen expression-individually and collectively impact treatment outcomes. Our analysis revealed that tuning CAR affinity modulates IL-2 production by balancing CAR T-cell proliferation and effector function. It also identified a novel multi-feature tuned treatment strategy for balancing selectivity and efficacy and provided insights into how spatial effects can impact relative treatment performance in different contexts. CARCADE facilitates deeper biological understanding of treatment design and could ultimately enable identification of promising treatment strategies to accelerate solid tumor CAR T-cell design-build-test cycles., 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 Prybutok, Yu, Leonard and Bagheri.)

Using a sample of about 10^{10}  J/ψ events collected at a center-of-mass energy sqrt[s]=3.097  GeV with the BESIII detector, the electromagnetic Dalitz decays J/ψ→e^{+}e^{-}π^{+}π^{-}η^{'}, with η^{'}→γπ^{+}π^{-} and η^{'}→π^{+}π^{-}η, have been studied. The decay J/ψ→e^{+}e^{-}X(1835) is observed with a significance of 15σ, and also an e^{+}e^{-} invariant-mass dependent transition form factor of J/ψ→e^{+}e^{-}X(1835) is presented for the first time. The intermediate states X(2120) and X(2370) are also observed in the π^{+}π^{-}η^{'} invariant-mass spectrum with significances of 5.3σ and 7.3σ. The corresponding product branching fractions for J/ψ→e^{+}e^{-}X, X→π^{+}π^{-}η^{'} [X=X(1835), X(2120), and X(2370)] are reported.

Background: Mutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion., Methods: Various mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration., Results: Piezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development., Conclusions: Piezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.

The Taiwanese cobra, Naja atra , is a clinically significant species of snake observed in the wild in Taiwan. Victims bitten by N. atra usually experience severe pain and local tissue necrosis. Although antivenom is available for treatment of cobra envenomation, its neutralization potency against cobra-induced necrosis is weak, with more than 60% of cobra envenoming patients developing tissue necrosis after antivenom administration. The present study found that cytotoxin (CTX) is a key component of N. atra venom responsible for cytotoxicity against myoblast cells. Anti-CTX IgY was generated in hens, and the spleens of these hens were used to construct libraries for the development of single chain variable fragments (scFv). Two anti-CTX scFv, S1 and 2S7, were selected using phage display technology and biopanning. Both polyclonal IgY and monoclonal scFv S1 reacted specifically with CTX in cobra venom. In a cell model assay, the CTX-induced cytolytic effect was inhibited only by monoclonal scFv S1, not by polyclonal IgY. Moreover, the neutralization potency of scFv S1 was about 3.8 mg/mg, approximately three times higher than that of conventional freeze-dried neurotoxic antivenom (FNAV). Collectively, these results suggest that scFv S1 can effectively neutralize CTX-induced cytotoxicity and, when combined with currently available antivenom, can improve the potency of the latter, thereby preventing tissue damage induced by cobra envenoming.

Tertiary lymphoid structures (TLS) are lymphoid aggregates in tumor tissues and their potential significance in clinical applications has not been fully elucidated in gastric cancer. We evaluated TLS and tumor-infiltrating immune cells using H&E and immunohistochemistry staining in the recruited patients with gastric cancer. The prognostic value of TLS was evaluated by Kaplan-Meier analysis and further validated using gene expression profiling. The alterations in gene mutation, copy number variance, and DNA methylation across the TLS signature subtypes were analyzed based on the Cancer Genome Atlas cohort. High TLS density was associated with improved overall survival and disease-free survival. A combination of TLS density and TNM stage obtained higher prognostic accuracy than the TNM stage alone. Tumors with high TLS density showed significantly higher infiltration of CD3+, CD8+, and CD20+ cells but lower infiltration of CD68+ cells. Transcriptomics analysis demonstrated that high TLS signature status was positively associated with the activation of inflammation-related and immune-related pathways. Multi-omics data showed a distinct landscape of somatic mutations, copy number variants, and DNA methylation across TLS signature subtypes. Our results indicated that TLS might link with enhanced immune responses, and represent an independent and beneficial predictor of resected gastric cancer. Multi-omics analysis further revealed key tumor-associated molecular alterations across TLS signature subtypes, which might help explore the potential mechanism of the interaction between TLS formation and cancer cells.

Purpose: We sought to evaluate the effects of concurrent temozolomide-based chemoradiation therapy on neurocognitive function in patients with low-grade glioma (LGG)., Materials/methods: We included adult patients with LGG who were treated postoperatively with radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). Patients were evaluated with comprehensive psychometric tests at baseline (prior to RT + TMZ) and at various time intervals following RT + TMZ. Baseline cognitive performance was analyzed by sex, age, education history, history of seizures, IDH mutation status, and 1p/19q codeletion status. Changes in neurocognitive performance were evaluated over time., Results: Thirty-seven LGG patients (mean age 43.6, 59.5% male) had baseline neurocognitive evaluation. Patients with an age > 40 years old at diagnosis and those with an education > 16 years demonstrated superior baseline verbal memory as assessed by HVLT. No other cognitive domains showed differences when stratified by the variables mentioned above. A total of 22 LGG patients had baseline and post RT + TMZ neurocognitive evaluation. Overall, patients showed no statistical difference between group mean test scores prior to and following RT + TMZ on all psychometric measures (with the exception of HVLT Discrimination)., Conclusion: Cognitive function remained stable following RT + TMZ in LGG patients evaluated prospectively up to 2 years. The anticipated analysis of RTOG 0424 will provide valuable neurocognitive outcomes specifically for high risk LGG patients treated with RT + TMZ., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this study, we analyzed if Actinomadura sp. RB99 produces siderophores that that could be responsible for the antimicrobial activity observed in co-cultivation studies. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and global natural product social molecular networking platform (GNPS) analysis of fungus-bacterium co-cultures resulted in the identification of five madurastatin derivatives (A1, A2, E1, F, and G1), of which were four new derivatives. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, as well as MS/MS data and their absolute structures were elucidated based on Marfey's analysis, DP4+ probability calculation and total synthesis. Structure analysis revealed that madurastatin E1 (2) contained a rare 4-imidazolidinone cyclic moiety and madurastatin A1 (5) was characterized as a Ga 3+ -complex. The function of madurastatins as siderophores was evaluated using the fungal pathogen Cryptococcus neoformans as model organism. Based on homology models, we identified the putative NRPS-based gene cluster region of the siderophores in Actinomadura sp. RB99., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Over the last years, the development of highly active and durable Pt-based electrocatalysts has been identified as the main target for a large-scale industrial application of fuel cells. In this work, we make a significant step ahead in this direction by preparing a high-performance electrocatalyst and suggesting new structure-activity design concepts which could shape the future of oxygen reduction reaction (ORR) catalyst design. For this, we present a new one-dimensional nanowire catalyst consisting of a L1 0 ordered intermetallic PtCo alloy core and compressively strained high-index facets in the Pt-rich shell. We find the nanoscale PtCo catalyst to provide an excellent turnover for the ORR and hydrogen evolution reaction (HER), which we explain from high-resolution transmission electron microscopy and density functional theory calculations to be due to the high ratio of Pt(221) facets. These facets include highly active ORR and HER sites surprisingly on the terraces which are activated by a combination of sub-surface Co-induced high Miller index-related strain and oxygen coverage on the step sites. The low dimensionality of the catalyst provides a cost-efficient use of Pt. In addition, the high catalytic activity and durability are found during both half-cell and proton exchange membrane fuel cell (PEMFC) operations for both ORR and HER. We believe the revealed design concepts for generating active sites on the Pt-based catalyst can open up a new pathway toward the development of high-performance cathode catalysts for PEMFCs and other catalytic systems.

Objective: The aim of this study was to use morphological parameters of mirror posterior communicating artery (PCoA) aneurysms to evaluate aneurysm rupture risk., Methods: The morphological parameters of 45 pairs of ruptured mirror PCoA aneurysms were analyzed. Conditional univariate and multivariate logistic regression of the following paired morphological parameters was performed: aneurysm with a daughter sac, aneurysm height, aneurysm width, neck width, internal carotid artery diameter, PCoA diameter, flow angle, PCoA angle, aspect ratio, bottleneck factor, size ratio, height/width ratio, fetal posterior cerebral artery, and aneurysm with height > width. A scoring system was established according to the odds ratios (ORs). The receiver operating characteristic was used to test the prediction accuracy of this scoring system in the authors' database of 523 PCoA aneurysms and the threshold value was used to define higher risk., Results: Aneurysm width (OR 1.676, p = 0.014), aneurysm with daughter sac (OR 7.775, p = 0.016), and aneurysm with height > width (OR 9.067, p = 0.012) were independent risk factors for rupture. The scoring system consisted of aneurysm width (1 point per mm), aneurysm with a daughter sac (5 points), and aneurysm with height > width (5 points). The area under the curve (AUC) of the scoring system was 0.842, and its threshold value was 7.97. A score ≥ 8 points was defined as higher risk. The AUC using this definition was 0.802., Conclusions: Aneurysm width, aneurysms with height > width, and aneurysms with a daughter sac were independent risk factors for PCoA aneurysm rupture. The scoring system devised in this study accurately predicts rupture risk.