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Objective: To assess the differences in scar outcomes between modified rotation-advancement techniques proposed by Drs. Mohler and Noordhoff, designed to address issues such as inadequate vertical lip length and scarring on the upper third of the lip in the original rotation-advancement technique., Design: Retrospective single-surgeon (RD) study., Patients: Consecutive non-syndromic children ( n  = 68) with unilateral complete cleft lip and palate., Interventions: Modified Mohler (columellar backcut reconstructed with C flap; n  = 34) and modified Noordhoff (lower, medially-created backcut reconstructed with laterally-based triangular skin flap; n  = 34) repairs., Mean Outcome Measures: Using 12-month postoperative frontal photographs, scar evaluations (overall and superior, middle, and inferior portions of the lip) were appraised by an assessment panel composed by independent professional and nonprofessional raters employing four validated qualitative scar assessment scales: Manchester Scar Scale, modified Scar-Rating Scale, Stony Brook Scar Evaluation Scale, and Visual Analog Scale. Quantitative computerized photogrammetric scar widths of the superior, middle, and inferior portions of the upper lip were also measured., Results: The modified Noordhoff method showed significantly (all P  < .001) better scar quality for the overall scar and superior portion of the scar in all four scales compared to the modified Mohler method, with no significant (all P  > .05) difference for the middle and lower portions. No significant difference (all P  > .05) was observed for photogrammetric scar width measurements., Conclusion: The modified Noordhoff technique provided better qualitative results for unilateral complete cleft lip-related scars compared to the modified Mohler technique., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To summarize and visualize the status quo, future hotspots and development trend of ED-related researches in China through bibliometric analysis., Methods: We searched the Web of Science Core Collection (WOSCC) and the database of Chinese National Knowledge Infrastructure (CNKI) for ED-related studies published in China from January 1, 2010 to August 14, 2023. Using the CiteSpace and VOSviewer softwares, we bibliometrically analyzed and visualized the related journals, regions, institutions, authors, key words, co-citations and other indexes of the identified studies., Results: A total of 2,465 ED-related studies were retrieved, with an increasing number of publications year by year, relatively more in the southeast region, with Sun Yat-sen University ranking the first in the number of published articles (n = 169), LIU Jihong (n = 73), WANG Tao (n = 71) and JIANG Rui (n = 49) as the top three prolific core authors. The first two Chinese journals with the most ED-related publications were Chinese Journal of Andrology (n = 320) and Journal of Sexual Medicine (n = 128), and the latter was also the mostly cited (n = 5 060). Keyword co-occurrence analysis showed that the highest-frequency Chinese terms included impotence, anxiety, andrology, expert consensus, experience of famous doctors, acupuncture, Earthworm protein (Chinese) and hypertension, and the English terms included erectile dysfunction, apoptosis, inflammation, fibrosis, risk and women., Conclusion: Recent years have wit-nessed a rapid development in ED-related studies in China, with the risk factors and patho-genic mechanisms of ED as hot topics. PDE5 inhibitors and adipose-derived stem cells for the treatment of ED have attracted long and continuous attention and will remain an important target of future research.

In response to environmental issues, upcycling has become a growing trend in the food industry. Aquasoya is a promising method to upcycle by-product from soybean processing due to its high protein contents and excellent emulsifying ability. In the present research, Aquasoya powder was used an emulsifier to incorporate the antioxidant compounds from perilla skin extract (PSE), namely rosmarinic acid, into oil-in-water (O/W) emulsion system and its physochemical stability was assessed. As a result, droplet size of the emulsion was smaller in PSE-incorporated emulsion (PO, 350.57 ± 9.60 b nm) than the emulsion without PSE (PX, 1045.37 ± 142.63 a nm). Centrifugal photosedimentometry analysis also revealed that the physical stability was significantly improved in PO, and the stability was maintained over 30 d of storage. Furthermore, as PO had a higher ABTS radical scavenging ability and showed slower initial lipid oxidation, it was concluded that PO has a higher antioxidant ability than PX. Conclusively, Aquasoya can be considered as an emulsifier in O/W emulsion with PSE because it can effectively integrate and stabilize the antioxidant substance derived from perilla skin.

Background: Oronasal fistula at the anterior hard palate is one of the common sequelae after cleft surgery, and the leakage negatively affects the patient's quality of life. Although several surgical techniques have been proposed for reconstruction, it remains challenging because of the scarred regional tissue with a high rate of fistula recurrence. In this study, we present the anterior oronasal fistula repair using a two-flap technique with an interpositional dermofat graft (DFG)., Methods: A retrospective review of anterior oronasal fistula repair performed by the senior author between April 2018 and August 2022 at the Craniofacial Center was conducted. Patients who underwent a fistula repair using the technique were further identified and investigated., Results: Thirty-four operations were performed using the technique, and 31 fistulas were completely closed, with a success rate of 91.2%. The fistula symptom improved but persisted postoperatively in 3 patients, of whom 2 patients underwent a second fistula repair using the same procedure, resulting in successful closure. Fistula recurrence was significantly correlated with fistula size (p = 0.04). The DFG was simultaneously utilized for nasal dorsum and/or vermillion reconstruction in 28 cases., Conclusion: The two-flap technique enabled tension-free approximation, and the interpositional DFG facilitated watertight closure of the fistula, resulting in a high success rate of anterior oronasal fistula repair. The fistula closure could be combined with other revisional procedures for cleft-related deformities, where the DFG was simultaneously utilized., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Importance: The incidence of brain metastasis is increasing in patients with metastatic breast cancer. Treatments to extend the control of brain metastasis are urgently required., Objective: To investigate whether the addition of an induction treatment of bevacizumab, etoposide, and cisplatin (BEEP) improves brain-specific progression-free survival (PFS) after whole-brain radiotherapy (WBRT)., Design, Setting, and Participants: This open-label, randomized, multicenter clinical trial assessed patients with brain metastases from breast cancer (BMBC) in Taiwan from September 9, 2014, to December 24, 2018, with survival follow-up until December 31, 2021. Key inclusion criteria included metastatic brain tumors not suitable for focal treatment, WBRT naivety, age 20 to 75 years, and at least 1 measurable brain metastatic lesion. The primary end point was brain-specific PFS, with an expected hazard ratio of 0.60, a 2-sided α ≤ .20, and power of 0.8., Interventions: Eligible patients were randomly assigned at a ratio of 2:1 to the experimental arm, which involved 3 cycles of BEEP followed by WBRT, or the control arm, which involved WBRT alone., Main Outcomes and Measures: The primary end point was the determination of brain-specific PFS by local investigators according to the Response Evaluation Criteria in Solid Tumors, version 1.1, the initiation of other brain-directed treatment after WBRT, or death. Other key end points included brain-specific objective response rate after 8 weeks of BEEP treatment or WBRT and 8-month brain-specific PFS rate, PFS, and overall survival., Results: A total of 118 patients with BMBC were randomized, with the intention-to-treat cohort comprising 112 patients. The median age was 56 years (range, 34-71 years), and 61 patients (54.5%) had ERBB2 (formerly HER2 or HER2/neu)-positive disease. The median (range) brain-specific PFS was 8.1 (0.3-29.5) vs 6.5 (0.9-25.5) months in the experimental and control arms, respectively (hazard ratio, 0.71; 95% CI, 0.44-1.13; P = .15; significant at predefined α ≤ .20). The brain-specific objective response rate at 2 months was not significantly different (BEEP treatment vs WBRT, 41.9% vs 52.6%), but the 8-month brain-specific PFS rate was significantly higher in the experimental group (48.7% vs 26.3%; P = .03). Adverse events were generally manageable with prophylactic granulocyte colony-stimulating factor treatment., Conclusions and Relevance: The findings show that induction BEEP before WBRT may improve the control of BMBC compared with using upfront WBRT, which could address an unmet need for an effective systemic treatment for intractable brain and extracranial metastases from metastatic breast cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT02185352.

Heterogeneous photocatalytic degradation of antibiotic involves the activation of antibiotic molecules and the photocatalytic oxidation process. However, the simultaneous improvement of these processes is still a challenge. Herein, S-scheme heterojunctions consisted of Cu 2 O nanocluster with defective WO 3 nanosheets were constructed for efficient photocatalytic degradation of levofloxacin (LVX). The typical CNS-5 composite (5 wt% Cu 2 O/WO 3 ) achieves an optimal LVX degradation efficiency of 97.9% within 80 min. The spatial charge separation and enhancement of redox capacity were realized by the formation of S-scheme heterojunction between Cu 2 O and WO 3 . Moreover, their interfacial interaction would lead to the loss of lattice oxygen and the generation of W 5+ sites. It is witnessed that the C-N of piperazine ring and CO of carboxylic acid in LVX are coordinated with W 5+ sites to build the electronic bridge to activate LVX, greatly promoting the further degradation. This work highlights the important role of selective coordination activation cooperated with S-type heterojunctions for the photocatalytic degradation and offers a new view to understand the degradation of antibiotics at molecular level., 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 © 2024 Elsevier Ltd. All rights reserved.)

Objective: To appraise the degree of intraoperative palatal lengthening with the modified Furlow small double-opposing Z-plasty (sDOZ)., Design: Retrospective single-surgeon (R.D.) study., Patients: Nonsyndromic children (n = 167) with Veau types I to IV cleft palates who underwent primary sDOZ palatoplasty., Interventions: Intraoperative measurements of palatal lengths and widths were collected using calipers, paper rulers, and metal rulers before the administration of local anesthetic solution and before the removal of the mouth gag (initial and final palatal dimensions, respectively)., Main Outcome Measures: Assessment of the intraoperative percentage change (difference between final and initial values) in surface palatal length, straight palatal length, and soft palatal length. Bivariate and multivariate analyses were performed to identify independent predictors (sex, age at surgery, Veau, Kernahan/ Stark, and Randall classifications, widest cleft width, presence of lateral relaxing incision, type of coverage with buccal fat flap, and postoperative complications) of soft palatal lengthening., Results: Surface palatal, straight palatal, and soft palatal lengths had an intraoperative increase of 8%, 14.7%, and 27.7%, respectively. The degree of intraoperative soft palatal lengthening significantly varied among Veau cleft types (I = II < III = IV). Veau type III and cleft lip/palate were independent positive predictors (P < .001) of soft palatal lengthening, while other tested variables were not correlated (P > .05) with this outcome., Conclusions: Overall intraoperative palatal lengthening occurs with the modified sDOZ palatoplasty, with differences within the spectrum of cleft palate deformity., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background Medical trainees must learn how to provide effective feedback as an essential communication skill, yet few models exist for training and assessing these skills. Objective To develop an observed structured feedback examination (OSFE) to provide feedback training to pediatric fellows and assess changes in skills and self-reported confidence. Methods This educational study was conducted from 2019 to 2020 at an academic children's hospital. Our team developed the OSFE and trained standardized feedback recipients and faculty. Fellows completed baseline self-assessments (31 items) on prior exposure to feedback training, application of skills, and confidence. They then participated in the OSFE, giving feedback to a standardized recipient using a standardized scenario, and were scored by faculty and recipients using a 15-item checklist for performance. Next, fellows participated in feedback training and received individualized feedback, after which they repeated the OSFE and confidence self-assessment. Three months later, fellows completed self-assessments on confidence and application of skills and another OSFE to assess retention. Descriptive statistics and signed rank sum test were used for analysis. Results Of 60 eligible fellows, 19 participated (32%), with 100% follow-up. After training and individualized feedback, all fellows improved feedback skills as measured by OSFE performance (mean change +0.89). All items, measured on a 5-point Likert scale, were sustained 3 months later (mean change +0.92). All fellows reported improved confidence in feedback knowledge (mean change +2.07 post, +1.67 3 months post). Conclusions Feedback training using simulation and individualized feedback moderately improved fellows' performance, confidence, and 3-month retention of feedback skills.

Background: Although several studies have shown that primary rhinoplasty in patients with cleft lip provides good outcomes with limited effect on nasal growth, the surgical procedure remains to be standardized. The purpose of this study was to evaluate the long-term outcome of primary semi-open rhinoplasty with Tajima reverse-U incision, compared with that of closed rhinoplasty., Methods: Consecutive nonsyndromic patients with complete bilateral cleft lip and palate (n = 52) who underwent primary semi-open rhinoplasty between 2001 and 2016 were reviewed. Patients who underwent primary closed rhinoplasty (n = 61) and control group individuals were recruited for comparison. Computer-based standardized measurements of 2D photographs and panel assessments by laypersons were collected and statistically analyzed., Results: In the comparative analysis at preschool age, semi-open rhinoplasty significantly improved the typical nasal deformities, including transversely oriented wide nostrils, short columella, and de-projected nasal tip, more effectively than closed rhinoplasty. Without major drawbacks, these parameters in the semi-open group were well maintained closer to those in the control group till skeletal maturity. After primary rhinoplasty, 54% of patients in the closed group and 4% in the semi-open group underwent intermediate rhinoplasty at preschool age., Conclusion: This study showed that the patients who underwent primary semi-open rhinoplasty achieved long-term and persistent outcomes that were closer to the normal nasal morphology compared with the patients treated with closed rhinoplasty, while avoiding intermediate rhinoplasty during the preschool to adolescent periods., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Intrahepatic cholangiocarcinoma (iCCA) is a subtype of CCA and has a high mortality rate and a relatively poor prognosis. However, studies focusing on increased cell motility and loss of epithelial integrity during iCCA progression remain relatively scarce. We collected seven fresh tumor samples from four patients to perform RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) to determine the transcriptome profile and chromatin accessibility of iCCA. The increased expression of cell cycle regulators, including PLK1 and its substrate MISP, was identified. Ninety-one iCCA patients were used to validate the clinical significance of PLK1 and MISP. The upregulation of PLK1 and MISP was determined in iCCA tissues. Increased expression of PLK1 and MISP was significantly correlated with tumor number, N stage, and lymphatic invasion in an iCCA cohort. Knockdown of PLK1 or MISP reduced trans-lymphatic endothelial migration and wound healing and affected focal adhesions in vitro. In cell‒cell junctions, MISP localized to adherens junctions and suppressed E-cadherin dimerization. PLK1 disrupted adherens junctions in a myosin-dependent manner. Furthermore, PLK1 and MISP promoted cell proliferation in vitro and tumorigenesis in vivo. In iCCA, PLK1 and MISP promote aggressiveness by increasing lymphatic invasion, tumor growth, and motility through the repression of E-cadherin adherens junctions., (© 2023. The Author(s).)

Background: C2H2-zinc finger transcription factors comprise one of the largest and most diverse gene superfamilies and are involved in the transcriptional regulation of flowering. Although a large number of C2H2 zinc-finger proteins (C2H2-ZFPs) have been well characterized in a number of model plant species, little is known about their expression and function in Coptis teeta . C. teeta displays two floral phenotypes (herkogamy phenotypes). It has been proposed that the C2H2-zinc finger transcription factor family may play a crucial role in the formation of floral development and herkogamy observed in C. teeta . As such, we performed a genome-wide analysis of the C2H2-ZFP gene family in C. teeta . Results: The complexity and diversity of C. teeta C2H2 zinc finger proteins were established by evaluation of their physicochemical properties, phylogenetic relationships, exon-intron structure, and conserved motifs. Chromosome localization showed that 95 members of the C2H2 zinc-finger genes were unevenly distributed across the nine chromosomes of C. teeta , and that these genes were replicated in tandem and segmentally and had undergone purifying selection. Analysis of cis-acting regulatory elements revealed a possible involvement of C2H2 zinc-finger proteins in the regulation of phytohormones. Transcriptome data was then used to compare the expression levels of these genes during the growth and development of the two floral phenotypes (F-type and M-type). These data demonstrate that in groups A and B, the expression levels of 23 genes were higher in F-type flowers, while 15 genes showed higher expressions in M-type flowers. qRT-PCR analysis further revealed that the relative expression was highly consistent with the transcriptome data. Conclusion: These data provide a solid basis for further in-depth studies of the C2H2 zinc finger transcription factor gene family in this species and provide preliminary information on which to base further research into the role of the C2H2 ZFPs gene family in floral development in C. teeta ., Competing Interests: Author Q-QH was employed by Zhongshan Zhongzhi Pharmaceutical Group Co., Ltd. The remaining 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 © 2024 Duan, Zhao, Yu, Xiang, Xiao, Cui, Hu, Baldwin, Lu and Liang.)

Asymmetric cell division (ACD) is a mechanism used by stem cells to maintain the number of progeny. However, the epigenetic mechanisms regulating ACD remain elusive. Here we show that BRD4, a BET domain protein that binds to acetylated histone, is segregated in daughter cells together with H3K56Ac and regulates ACD. ITGB1 is regulated by BRD4 to regulate ACD. A long noncoding RNA (lncRNA), LIBR (LncRNA Inhibiting BRD4), decreases the percentage of stem cells going through ACD through interacting with the BRD4 mRNAs. LIBR inhibits the translation of BRD4 through recruiting a translation repressor, RCK, and inhibiting the binding of BRD4 mRNAs to polysomes. These results identify the epigenetic regulatory modules (BRD4, lncRNA LIBR) that regulate ACD. The regulation of ACD by BRD4 suggests the therapeutic limitation of using BRD4 inhibitors to treat cancer due to the ability of these inhibitors to promote symmetric cell division that may lead to tumor progression and treatment resistance., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: This multicenter, phase II randomized, non-inferiority study reports from the first prospective two-armed randomized control trial that compared the efficacy, safety, and quality of life (QoL) of pegylated liposomal doxorubicin (PLD)-based and epirubicin-based as adjuvant chemotherapy for stage I-II human epidermal growth factor receptor 2 (HER2)-negative breast cancer., Methods: Patients with stage I/II HER2-negative breast cancer received PLD (37.5 mg/m2, Q3W, 5 cycles, LC arm) plus cyclophosphamide (600 mg/m2) or epirubicin (90 mg/m2, Q3W, 4 cycles, EC arm) plus cyclophosphamide (600 mg/m2). Randomization was stratified by lymph node and ER and PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and QoL. QoL was assessed using the EORTC-QLQ-C30 and QLQ-BR23 questionnaires., Results: A total of 256 patients were assigned to LC (n = 148) and EC (n = 108). There was no difference in 5-year DFS and OS rate between the two groups. LC-based adjuvant regimens had significantly less alopecia and low-grade 3-4 hematologic adverse events (AEs). Significantly improved QoL was observed in the LC arm during and after treatment for symptoms including fatigue, nausea and vomiting, and systemic therapy side effects., Conclusion: Comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II HER2-negative breast cancer was observed. There was no difference in the 5-year DFS and OS rates between the two treatment arms. However, low-grade 3-4 AEs and a trend of favorable QoL symptom scales were observed in the LC arm, suggesting that PLD-containing regimen could become a new standard treatment for early-stage HER2-negative breast cancer patients., (© 2024 S. Karger AG, Basel.)

Introduction: The Chang Gung Forum has been dedicated to the care of craniofacial anomalies since 2000. This annual continuing medical education program focuses on orofacial cleft and surgery-first orthognathic surgery by providing up-to-date information and management guidelines. This study explored how the Chang Gung Forum has influenced medical perspectives, decisions, and practices in a multidisciplinary craniofacial team., Methods: Between 2000 and 2022, 20 Chang Gung Forums have been held. A questionnaire was distributed among 170 attendees who had participated in the forum more than once. The questionnaire collected information on the participants' experiences and levels of satisfaction with the educational program and whether or how it had influenced their clinical practice., Results: Valid responses from 86 attendees (response rate, 50.6%) who had participated more than once were collected and analyzed. The overall satisfaction rate of the Chang Gung Forum based on the respondents' most recent visits was 4.28 ± 0.63 out of 5. Of the respondents, 90.9% acknowledged changes in their clinical practice, with modifications in surgery plans and decisions being the most notable (48.5%). In addition, comprehension increased throughout years of attending the annual forum (P < 0.001)., Conclusion: The Chang Gung Forum has contributed markedly to the community of congenital craniofacial anomalies. The program will continue providing updated information and influencing the clinical decision-making of health care professionals., Competing Interests: Conflicts of interest and sources of funding: This work was supported in part by a grant from the Craniofacial Research Center, Taoyuan Chang Gung Memorial Hospital (CMRPG3J0823, CMRPG3L0361, CORPG3M0211)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study evaluated protective behaviors against coronavirus disease-2019 (COVID-19) and related factors in individuals with depressive symptoms., Methods: This cross-sectional study included data from the 2020 Korean Community Health Survey. Depressive symptoms, COVID- 19 protection behaviors, and related factors were investigated in 228,485 people. Chi-square test and logistic regression analysis were used to analyze categorical variables. Statistical analysis was performed using SPSS software (version 27.0)., Results: In the study, 3.9% (n=8,970) had depressive symptoms. The prevalence of depressive symptoms was higher in individuals in their 19-39 years , and ≥60s than in those in their 40-59 years (p<0.001). Lower education level and household income were associated with a higher prevalence of depression (p<0.001). Among the various occupations, service workers had the highest prevalence of depressive symptoms (p<0.001). Individuals with depressive symptoms were less likely to adopt protective behaviors against COVID-19 (p<0.001) or exhibit concerns regarding death and economic damage (p<0.001) compared to individuals without depressive symptoms. Individuals with depressive symptoms were more likely to have unhealthy behaviors than those without depressive symptoms (p<0.001). Individuals with depressive symptoms considered that the COVID-19 response by the government and other organizations was inadequate (p<0.001)., Conclusion: During the COVID-19 pandemic, individuals with depressive symptoms faced greater challenges in adopting protective behaviors. Therefore, it is crucial to develop strategies to protect people with depressive symptoms during another pandemic in the future.

Objective: To determine the cost-effectiveness of surveillance imaging with PET/CT scan among patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma., Study Design: Cost-effectiveness analysis., Setting: Oncologic care centers in the United States with head and neck oncologic surgeons and physicians., Methods: We compared the cost-effectiveness of 2 posttreatment surveillance strategies: clinical surveillance with the addition of PET/CT scan versus clinical surveillance alone in human papillomavirus-positive oropharyngeal squamous cell carcinoma patients. We constructed a Markov decision model which was analyzed from a third-party payer's perspective using 1-year Markov cycles and a 30-year time horizon. Values for transition probabilities, costs, health care utilities, and their studied ranges were derived from the literature., Results: The incremental cost-effectiveness ratio for PET/CT with clinical surveillance versus clinical surveillance alone was $89,850 per quality-adjusted life year gained. Flexible fiberoptic scope exams during clinical surveillance would have to be over 51% sensitive or PET/CT scan cost would have to exceed $1678 for clinical surveillance alone to be more cost-effective. The willingness-to-pay threshold at which imaging surveillance was equally cost-effective to clinical surveillance was approximately $80,000/QALY., Conclusion: Despite lower recurrence rates of human papillomavirus-positive oropharyngeal cancer, a single PET/CT scan within 6 months after primary treatment remains a cost-effective tool for routine surveillance when its cost does not exceed $1678. The cost-effectiveness of this strategy is also dependent on the clinical surveillance sensitivity (flexible fiberoptic pharyngoscopy), and willingness-to-pay thresholds which vary by country., (© 2023 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Flavonoids, which contain a benzo-γ-pyrone (C6-C3-C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of 7,8-dihydroxyflavone (7,8-DHF) and 7-hydroxyflavone (7-HF) in H 2 O 2 , lipopolysaccharide (LPS), or tert-butyl hydroperoxide (t-BHP)-induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8-DHF and 7-HF were firstly evaluated by 2,2-azinobis-3-ethyl-benzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H 2 O 2 , LPS, or t-BHP-induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7-HF and 7,8-DHF were initially investigated by western blot. Our results showed that 7,8-DHF possessed stronger free-radical scavenging capacity than 7-HF. Both 7,8-DHF and 7-HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H 2 O 2 , LPS, or t-BHP-induced RAW264.7 cells, respectively. And 7,8-DHF exerted a better antioxidant effect than 7-HF, especially in t-BHP-induced oxidative stress. Mechanically, 7,8-DHF prevented the activation of poly ADP-ribosepolymerase and caspase-3, meanwhile markedly upregulated the expression of HO-1 protein in t-BHP-induced oxidative stress. These results suggested that 7,8-DHF might serve as a potential pharmaceutical drug against oxidative stress injury., (© 2023 Wiley Periodicals LLC.)

Occupations are typically characterized in nominal form, a format that limits options for hypothesis testing and data analysis. We drew upon ratings of knowledge, skills, and abilities for 966 occupations listed in the US Department of Labor's Occupational Classification Network (O*NET) database to create an accessible, standardized multidimensional space in which occupations can be quantitatively localized and compared. Principal component analysis revealed that the occupation space comprises three main dimensions that correspond to (1) the required amount of education and training, (2) the degree to which an occupation falls within a science, technology, engineering, and mathematics (STEM) discipline versus social sciences and humanities, and (3) whether occupations are more mathematically or health related. Additional occupational spaces reflecting cognitive versus labor-oriented categories were created for finer-grained characterization of dimensions within occupational sets defined by higher or lower required educational preparation. Data-driven groupings of related occupations were obtained with hierarchical cluster analysis (HCA). Proof-of-principle was demonstrated with a real-world dataset (470 participants from the Nathan Kline Institute - Rockland Sample; NKI-RS), whereby verbal and non-verbal abilities-as assessed by standardized testing-were related to the STEM versus social sciences and humanities dimension. Visualization of Latent Components Assessed in O*Net Occupations (VOLCANO) is provided to the research community as a freely accessible tool, along with a Shiny app for users to extract quantitative scores along the relevant dimensions. VOLCANO brings much-needed standardization to unwieldy occupational data. Moreover, it can be used to create new occupational spaces customized to specific research domains., (© 2023. The Psychonomic Society, Inc.)

Differential scanning fluorimetry (DSF) is a widely used technique for determining the apparent melting temperature (Tma) of a purified protein. Here, we present a protocol for performing and optimizing DSF experiments. We describe steps for designing and performing the experiment, analyzing data, and optimization. We provide benchmarks for typical Tmas and ΔTmas, standard assay conditions, and upper and lower limits of commonly altered experimental variables. We also detail common pitfalls of DSF and ways to avoid, identify, and overcome them., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

A series of dehydrated MoS 2 /UiO-66(SH) 2 (MS/UiS) composites has been prepared as photocatalysts for N 2 fixation. Typically, 10% MS/UiS exhibits the best performance with an NH 4 + yield rate of 54.08 μmol∙g -1 ∙h -1 . 15 N isotope test confirmed that the sample 10% MS/UiS was most effective for reducing N 2 to ammonia. Such enhanced activity was due to the presence of abundant unsaturated Zr and Mo sites which would synergistically promote the adsorption and activation of N 2 . The photogenerated electrons would transfer to the unsaturated Zr-O clusters while part of photogenerated electrons at the interface migrate to MS via Mo VI -O interactions between MS and UiS. These two electron transfer pathways effectively promote the separation of photogenerated carriers. The activated N 2 is reduced to ammonia by the synergistic effect of protonated hydrogen and photogenerated electrons. Finally, a possible N 2 fixation mechanism is proposed which emphasizes the significant roles of nitrogen activation and interface interaction in composites photocatalyst for improving photocatalytic performance., 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 © 2023. Published by Elsevier Inc.)

Stretchable interconnects with miniature widths are vital for the high-density integration of deformable electronic components on a single substrate for targeted data logic or storage functions. However, it is still challenging to attain high-resolution patternability of stretchable conductors with robust circuit fabrication capability. Here, we report a self-assembled silver nanofilm firmly interlocked by an elastomeric nanodielectric that can be photolithographically patterned into microscale features while preserving high stretchability and conductivity. Both silver and dielectric nanofilms are fabricated by layer-by-layer assembly, ensuring wafer-scale uniformity and meticulous control of thicknesses. Without any thermal annealing, the as-fabricated nanofilms from silver nanoparticles (AgNPs) exhibit conductivity of 1.54 × 10 6 S m -1 and stretchability of ∼200%, which is due to the impeded crack propagation by the underlying PU nanodielectrics. Furthermore, it is revealed that AgNP microstrips defined by photolithography show higher stretchability when their widths are downscaled to 100 μm owing to confined cracks. However, further scaling restricts the stretchability, following the early development of cracks cutting across the strip. In addition, the resistance change of these silver interconnects can be decreased using serpentine architectures. As a demonstration, these self-assembled interconnects are used as stretchable circuit boards to power LEDs.

Abstract: Musculoskeletal anatomy education is essential to many healthcare providers but has consistently been considered difficult for various reasons. Traditional methods have focused on in-person cadaveric teaching, which became inaccessible during the COVID-19 pandemic; therefore, new teaching methods were developed to address this gap in education. This project implemented novel virtual livestream musculoskeletal anatomy teaching methodology with cadaveric prosections and evaluated the efficacy of this modality compared with traditional in-person cadaveric teaching. A targeted musculoskeletal anatomy curriculum was developed and delivered via livestream to 12 Canadian physiatry residents. Upon completing the virtual curriculum, residents completed an anonymous survey assessing this new virtual livestream cadaveric methodology compared with previous experiences with traditional in-person anatomy teaching. The survey response rate was 92%. Most participants (73%) rated the virtual livestream sessions as better than traditional in-person teaching. Reasons included better visualization of cadaveric anatomy and easy discussion among the group. T test analysis comparing both methods demonstrated the livestream method was equivalent or better across several domains. Virtual livestream teaching is a viable method for teaching the important subject of musculoskeletal anatomy. Educators should consider how to best integrate this approach into future anatomy curricula., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A retrospective case-control study to determine the role of pre-operative systemic and local nutritional factors on patients developing a surgical site infection (SSI) after posterior lumbar interbody fusion (PLIF). Surgical site infection after PLIF remains a substantial cause of morbidity. The literature demonstrates the prognosis of surgical patients is associated with pre-operative nutritional status that not only includes systemic nutritional factors, such as prognostic nutritional index (PNI), body mass index (BMI), and serum albumin, but also local nutritional factors, such as subcutaneous fat thickness at the surgical site, including absolute fat thickness and relative fat thickness. However, the role of pre-operative nutrition status in SSI after PLIF surgery remains unclear. Patients and Method: A retrospective review was performed on a consecutive cohort of 766 consecutive adult patients who underwent PLIF surgery for lumbar degenerative conditions between 2020 and 2021 at Second Xiangya Hospital. Previously identified risk factors as well as systemic and local nutritional factors nutritional factors were collected. Results: Among the 766 patients, 38 had post-operative SSI including 15 superficial SSI and 23 deep SSI. Univariable analysis showed that body weight, BMI, PNI, serum albumin, and relative fat thickness differed between the SSI and non-SSI groups. Multivariable logistic regression analysis showed that pre-operative PNI and relative fat thickness were independently associated with SSI after PLIF surgery. Conclusions: Lower pre-operative PNI and higher relative fat thickness are independent risk factors for developing deep SSI after PLIF.

Gene expression signatures provide valuable information to guide postoperative treatment in breast cancer (BC) patients. However, genetic tests are prohibitively expensive for the majority of BC patients. Immunohistochemical staining (IHC) subtype classification system has been widely used for treatment guideline and is affordable to most BC patients. We aimed to revise immunohistochemical staining (IHC) subtyping to better match gene expression-based Prediction Analysis of Microarray 50 (PAM50) subtyping. Real world data of 372 BC patients were recruited in the Tri-Service General Hospital between Jan 2019 and Dec 2021. Clinical pathological information, blood, twelve pathological tissue slide samples, and fresh surgical tumor specimens were collected to examine IHC and PAM50. Current IHC subtyping (cIHC) tends to misclassify PAM50-based luminal A (lum A) to luminal B (lum B) by 35.81%, PAM50-lum B to PAM50-lum A by 9.09%, PAM50-Her2-enriched to lum B by 61.11%, PAM50-based Her2-enriched to lum B by 61.11%, and PAM50-based basal-like to lum B by 33.33%. We used random forest to identify estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), and Ki-67 status as the best indicators for revised IHC subtyping (rIHC4) and revised the classification rules by stratified analysis and prediction efficacy. rIHC4 increased the concordance rate for PAM50 subtypes from 68.3% to 74.7%. Both sensitivity and precision increased in most rIHC4 subtypes. Sensitivity increased from 33.3% to 87.4% in the Her2-enriched subtype; precision increased more evidently in the basal-like and lum B subtypes, from 71.4% to 83.3% and 57% to 65.1%, respectively. Our rIHC4 subtyping improved consistency with the PAM50 subtype, which could improve clinical management of BC patients without increasing medical expense., Competing Interests: None., (AJCR Copyright © 2023.)

Atomically thin sheets ( e.g. , graphene and monolayer molybdenum disulfide) are ideal optical and reaction platforms. They provide opportunities for deciphering some important and often elusive photocatalytic phenomena related to electronic band structures and photo-charges. In parallel, in such thin sheets, fine tuning of photocatalytic properties can be achieved. These include atomic-level regulation of electronic band structures and atomic-level steering of charge separation and transfer. Herein, we review the physics and chemistry of electronic band structures and photo-charges, as well as their state-of-the-art characterization techniques, before delving into their atomic-level deciphering and mastery on the platform of atomically thin sheets.

Background: The hypoxia-responsive long non-coding RNA, RP11-367G18.1, has recently been reported to induce histone 4 lysine 16 acetylation (H4K16Ac) through its variant 2; however, the underlying molecular mechanism remains poorly understood., Methods: RNA pull-down assay and liquid chromatography-tandem mass spectrometry were performed to identify RP11-367G18.1 variant 2-binding partner. The molecular events were examined utilizing western blot analysis, real-time PCR, luciferase reporter assay, chromatin immunoprecipitation, and chromatin isolation by RNA purification assays. The migration, invasion, soft agar colony formation, and in vivo xenograft experiments were conducted to evaluate the impact of RP11-367G18.1 variant 2-YY1 complex on tumor progression., Results: In this study, RNA sequencing data revealed that hypoxia and RP11-367G18.1 variant 2 co-regulated genes were enriched in tumor-related pathways. YY1 was identified as an RP11-367G18.1 variant 2-binding partner that activates the H4K16Ac mark. YY1 was upregulated under hypoxic conditions and served as a target gene for hypoxia-inducible factor-1α. RP11-367G18.1 variant 2 colocalized with YY1 and H4K16Ac in the nucleus under hypoxic conditions. Head and neck cancer tissues had higher levels of RP11-367G18.1 and YY1 which were associated with poor patient outcomes. RP11-367G18.1 variant 2-YY1 complex contributes to hypoxia-induced epithelial-mesenchymal transition, cell migration, invasion, and tumorigenicity. YY1 regulated hypoxia-induced genes dependent on RP11-367G18.1 variant 2., Conclusions: RP11-367G18.1 variant 2-YY1 complex mediates the tumor-promoting effects of hypoxia, suggesting that this complex can be targeted as a novel therapeutic strategy for cancer treatment., (© 2023. The Author(s).)

Background: The post-palatoplasty velopharyngeal function needs to be evaluated through long-term follow-up, but such reports are limited in the literature and there has been no consensus as to which surgical technique yields optimal velopharyngeal function with minimum complication rate. This study aimed to evaluate the long-term outcome of the modified Furlow palatoplasty using small double-opposing Z-plasty (small-DOZ)., Methods: A retrospective review of consecutive patients who received palatoplasty performed by the senior author between January 2000 and March 2014 was conducted. Non-syndromic patients who underwent palatoplasty before the age of 18 months and followed-up until at least 9 years of age were included. Comparisons between the small-DOZ and two-flap methods for soft palate repair were made., Results: A total of 196 small-DOZ and 167 two-flap palatoplasty patients were eligible in the study. Among the small-DOZ palatoplasty patients, 1 patient (0.5%) developed oronasal fistula, and 18 patients (9.2%) received velopharyngeal insufficiency (VPI) surgery (10 patients at preschool age and 8 at nine years of age). Compared with the small-DOZ palatoplasty, the oronasal fistula rate, VPI surgery rate, and the need for myringotomy tube insertion were significantly higher in the two-flap group (p =0.01, <0.01, <0.01, respectively). Patients who developed oronasal fistula had significantly higher likelihood of having velopharyngeal insufficiency (p < 0.01)., Conclusion: The small-DOZ provided successful palatal repair with low rates of oronasal fistula and VPI in the long-term. Wound closure under minimal tension facilitated to avoid oronasal fistula. Reconstruction of the functional muscle sling enabled to achieve normal velopharyngeal function with favorable speech outcome and middle ear function., Competing Interests: Conflicts of interest statement: No conflicting relationship exists for all authors., (Copyright © 2023 by the American Society of Plastic Surgeons.)

With potent herbicidal activity, biocatalysis synthesis of L-glufosinate has drawn attention. In present research, NAP-Das2.3, a deacetylase capable of stereoselectively resolving N-acetyl-L-glufosinate to L-glufosinate mined from Arenimonas malthae, was heterologously expressed and characterized. In Escherichia coli, NAP-Das2.3 activity only reached 0.25 U/L due to the formation of inclusive bodies. Efficient soluble expression of NAP-Das2.3 was achieved in Pichia pastoris. In shake flask and 5 L bioreactor fermentation, NAP-Das2.3 activity by recombinant P. pastoris reached 107.39 U/L and 1287.52 U/L, respectively. The optimum temperature and pH for N-acetyl-glufosinate hydrolysis by NAP-Das2.3 were 45 °C and pH 8.0, respectively. The K m and V max of NAP-Das2.3 towards N-acetyl-glufosinate were 25.32 mM and 19.23 μmol mg -1  min -1 , respectively. Within 90 min, 92.71% of L-enantiomer in 100 mM racemic N-acetyl-glufosinate was converted by NAP-Das2.3. L-glufosinate with high optical purity (e.e. P above 99.9%) was obtained. Therefore, the recombinant NAP-Das2.3 might be an alternative for L-glufosinate biosynthesis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: International travel had been radically disrupted by coronavirus disease 2019 (COVID-19), leaving traditional medical conferences on a 2-year hiatus. The International Craniofacial Chang Gung Group (ICC) was thus created to disseminate knowledge related to craniofacial surgery. This study aimed to reveal how webinars fundamentally transformed the traditional format of medical conferences., Materials and Method: In total, 64 ICC webinars held between December 13, 2020, and May 21, 2023, were documented and reviewed. A questionnaire was designed and sent to ICC members. The questionnaire collected information on attitudes and habits relating to videoconferencing in general before and after the start of COVID-19 and on the ICC webinars specifically. Responses were analyzed to inform our understanding of respondents' experience and satisfaction with the webinars., Results: The webinars covered a variety of topics related to craniofacial surgery. In total, 64 webinars were included for analysis. The mean number of attendees at each webinar was 86.7. In total, 111 respondents were more satisfied (4.25 ± 0.72 out of 5) with ICC webinars than with other media of online meetings ( P < 0.001). In total, 89.2% of respondents were willing to continue attending ICC webinars after COVID-19 restrictions have been lifted., Conclusions: Webinars are an effective format for imparting knowledge, especially in the ICC, and will become key in continuing medical education., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: BAT1706 is a proposed biosimilar of bevacizumab (Avastin®). We aimed to compare the efficacy and safety of BAT1706 with that of EU-sourced reference bevacizumab (EU-bevacizumab) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC)., Methods: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (BAT1706 arm) or EU-bevacizumab plus paclitaxel and carboplatin (EU-bevacizumab arm) given every 3 weeks for six cycles, followed by maintenance therapy with BAT1706 or EU-bevacizumab. The primary endpoint was overall response rate at week 18 (ORR 18 ). Clinical equivalence was demonstrated if the 90% confidence interval (CI) of the BAT1706:EU-bevacizumab ORR 18 risk ratio was contained within the predefined equivalence margins of 0.75-1.33 (China National Medical Products Administration requirements), or 0.73-1.36 (US Food and Drug Administration), or if the 95% CI of the ORR 18 risk difference between treatments was contained within the predefined equivalence margin of -0.12 to 0.15 (EMA requirements)., Results: In total, 649 randomized patients (BAT1706, n = 325; EU-bevacizumab, n = 324) received at least one cycle of combination treatment. The ORR 18 was comparable between the BAT1706 and EU-bevacizumab arms (48.0% and 44.5%, respectively). The ORR 18 risk ratio of 1.08 (90% CI: 0.94-1.24) and the ORR 18 risk difference of 0.03 (95% CI: -0.04 to 0.11) were within the predefined equivalence margins, demonstrating the biosimilarity of BAT1706 and EU-bevacizumab. The safety profile of BAT1706 was consistent with that of EU-bevacizumab and no new safety signals were observed., Conclusion: In patients with advanced nonsquamous NSCLC, BAT1706 demonstrated clinical equivalence to EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Natural history of hepatitis B or C is comprised of multiple milestones such as liver cirrhosis and liver cancer. To fully characterize its natural course, semicompeting risks represent a common problem where liver cirrhosis and liver cancer are both of interest, but only the former may be censored by the latter. Copula, frailty and multistate models serve as well-established analytics for semicompeting risks. Here, we cast the semicompeting risks in a mediation framework, with liver cirrhosis as a mediator and liver cancer as an outcome. We define the indirect and direct effects as the effects of an exposure on the liver cancer incidence mediated and not mediated through liver cirrhosis, respectively. With the estimands derived as conditional probabilities, we derive respective expressions under the copula, frailty, and multistate models. Next, we propose estimators based on nonparametric maximum likelihood or U-statistics and establish their asymptotic results. Numerical studies demonstrate that the efficiency of copula models leads to potential bias due to model misspecification. Moreover, the robustness of frailty models is accompanied by a loss in efficiency, and multistate models balance the efficiency and robustness. We demonstrate the utility of the proposed methods by a hepatitis study, showing that hepatitis B and C lead to a higher incidence of liver cancer by increasing liver cirrhosis incidence. Thus, mediation modeling provides a unified framework that accommodates various semicompeting risks models., (© 2023 John Wiley & Sons Ltd.)

Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest.

Importance: An intensive lifestyle intervention (ILI) has been shown to improve diabetes management and physical function. These benefits could lead to better labor market outcomes, but this has not been previously studied., Objective: To estimate the association of an ILI for weight loss in type 2 diabetes with employment, earnings, and disability benefit receipt during and after the intervention., Design, Setting, and Participants: This cohort study included participants with type 2 diabetes and overweight or obesity and compared an ILI with a control condition of diabetes support and education. Data for the original trial were accrued from August 22, 2001, to September 14, 2012. Trial data were linked with Social Security Administration records to investigate whether, relative to the control group, the ILI was associated with improvements in labor market outcomes during and after the intervention period. Difference-in-differences models estimating relative changes in employment, earnings, and disability benefit receipt between the ILI and control groups were used, accounting for prerandomization differences in outcomes for linked participants. Outcome data were analyzed from July 13, 2020, to May 17, 2023., Exposure: The ILI consisted of sessions with lifestyle counselors, dieticians, exercise specialists, and behavioral therapists on a weekly basis in the first 6 months, decreasing to a monthly basis by the fourth year, designed to achieve and maintain at least 7% weight loss. The control group received group-based diabetes education sessions 3 times annually during the first 4 years, with 1 annual session thereafter., Main Outcomes and Measures: Employment and receipt of federal disability benefits (Supplemental Security Income and Social Security Disability Insurance), earnings, and disability benefit payments from 1994 through 2018., Results: A total of 3091 trial participants were linked with Social Security Administration data (60.1% of 5145 participants initially randomized and 97.0% of 3188 of participants consenting to linkage). Among the 3091 with fully linked data, 1836 (59.4%) were women, and mean (SD) age was 58.4 (6.5) years. Baseline clinical and demographic characteristics were similar between linked participants in the ILI and control groups. Employment increased by 2.9 (95% CI, 0.3-5.5) percentage points for the ILI group relative to controls (P = .03) with no significant relative change in disability benefit receipt (-0.9 [95% CI, -2.1 to 0.3] percentage points; P = .13)., Conclusions and Relevance: The findings of this cohort study suggest that an ILI to prevent the progression and complications of type 2 diabetes was associated with higher levels of employment. Labor market productivity should be considered when evaluating interventions to manage chronic diseases.

Introduction: Glioblastoma (GBM) is the most common invasive brain tumor composed of diverse cell types with poor prognosis. The highly complex tumor microenvironment (TME) and its interaction with tumor cells play important roles in the development, progression, and durability of GBM. Angiogenic and immune factors are two major components of TME of GBM; their interplay is a major determinant of tumor vascularization, immune profile, as well as immune unresponsiveness of GBM. Given the ineffectiveness of current standard therapies (surgery, radiotherapy, and concomitant chemotherapy) in managing patients with GBM, it is necessary to develop new ways of treating these lethal brain tumors. Targeting TME, altering tumor ecosystem may be a viable therapeutic strategy with beneficial effects for patients in their fight against GBM. Materials and Methods: Given the potential therapeutic effects of cannabidiol (CBD) in a wide spectrum of diseases, including malignancies, we tested, for the first time, whether inhalant CBD can inhibit GBM tumor growth using a well-established orthotopic murine model. Optical imaging, histology, immunohistochemistry, and flow cytometry were employed to describe the outcomes such as tumor progression, cancer cell signaling pathways, and the TME. Results: Our findings showed that inhalation of CBD was able to not only limit the tumor growth but also to alter the dynamics of TME by repressing P-selectin, apelin, and interleukin (IL)-8, as well as blocking a key immune checkpoint-indoleamine 2,3-dioxygenase (IDO). In addition, CBD enhanced the cluster of differentiation (CD) 103 expression, indicating improved antigen presentation, promoted CD8 immune responses, and reduced innate Lymphoid Cells within the tumor. Conclusion: Overall, our novel findings support the possible therapeutic role of inhaled CBD as an effective, relatively safe, and easy to administer treatment adjunct for GBM with significant impacts on the cellular and molecular signaling of TME, warranting further research.

The transformation of astrocytes into reactive states constitutes a biological response of the central nervous system under a variety of pathological insults. Astrocytes display diverse homeostatic identities that are developmentally predetermined and regionally specified. Upon transformation into reactive states associated with neurodegenerative diseases and other neurological disorders, astrocytes acquire diverse reactive phenotypes. However, it is not clear whether their reactive phenotypes are dictated by region-specific homeostatic identity or by the nature of an insult. To address this question, region-specific gene expression profiling was performed for four brain regions (cortex, hippocampus, thalamus, and hypothalamus) in mice using a custom NanoString panel consisting of selected sets of genes associated with astrocyte functions and their reactivity for five conditions: prion disease, traumatic brain injury, brain ischemia, 5XFAD Alzheimer's disease model and normal aging. Upon transformation into reactive states, genes that are predominantly associated with astrocytes were found to respond to insults in a region-specific manner. Regardless of the nature of the insult or the insult-specificity of astrocyte response, strong correlations between undirected GSA (gene set analysis) scores reporting on astrocyte reactivity and on their homeostatic functions were observed within each individual brain region. The insult-specific gene expression signatures did not separate well from each other and instead partially overlapped, forming continuums. The current study demonstrates that region-specific homeostatic identities of astrocytes are important for defining their response to pathological insults. Within region-specific populations, reactive astrocytes show continuums of gene expression signatures, partially overlapping between individual insults.

Earth's primordial atmosphere was rich in ammonia and methane. To understand the evolution of the atmosphere, these two gases were used to make photoredox-active nitrogen-doped carbon (NDC). Photocatalysts such as NDC might play an important role in the development of geological and atmospheric chemistry during the Archean era. This study describes the synthesis of NDC directly from NH 3 and CH 4 gases. The photocatalyst product can be used to selectively synthesize imines by photo-oxidization of amines, producing H 2 O 2 simultaneously in the photoreduction reaction. Our findings shed light on the chemical evolution of the Earth., (© 2023 Wiley-VCH GmbH.)

OX40 (CD134), a member of the TNF receptor superfamily, is a widely studied costimulatory immune checkpoint. Several OX40 agonistic antibodies are in the clinical stage for cancer treatment, among which PF-04518600 is the leader and currently in phase II trial. It has been recognized that one potential mode of action for anti-OX40 antibodies is the deletion of intratumoral Tregs. Thus, a novel human anti-OX40 antibody, BAT6026, was generated with enhanced antibody dependent cellular cytotoxicity (ADCC) via fucose deletion to strengthen its Treg depletion activity. This characteristic of BAT6026 differentiates it from other previously reported anti-OX40 antibodies in the field of tumor therapy. The affinity of BT6026 to OX40 was 0.28nM, approximately 8 times stronger than that of PF-04518600. BAT6026 effectively competed for the binding of ligand OX40L to OX40, whereas PF-04518600 only partially competed. Moreover, compared to PF-04518600, BAT6026 activated T cells more effectively when clustered by FcγRs engagement and stimulated SEB-pretreated PBMCs to secrete IL-2 cytokines in vitro . In addition, BAT6026 demonstrated stronger anti-tumor activity than PF-04518600 in an OX40-humanized mouse MC38 tumor model. BAT6026 also showed a significantly synergistic effect on tumor inhibition when combined treatment with PD-1 antibody. Analysis of tumor-infiltrating T cells revealed that BAT6026 treatment significantly reduced Treg cells and increased CD8+ T cells in tumor. Preclinical safety assessment in non-human primates demonstrated a good safety profile for BAT6026. Together these data warrant further development of BAT6026 into clinical trials for patients with cancer., Competing Interests: All authors are employees of Bio-Thera Solutions Guangzhou, China. The authors declare that this study received funding from Bio-Thera Solutions. The funder had the following involvement in the study: study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication., (Copyright © 2023 Liang, Zheng, Liu, Mei, Zhou, Xiao, Qin, Yue, Lin, Liu, Li and Yu.)

The antibacterial secondary metabolites of the fungus Penicillium chrysogenum associated with the beetle Aspongopus chinensis were investigated through chromatographic fractionation methods of ethyl acetate extracts of the fungal cultures. Five compounds were isolated, and their structures were determined as emodin, 4-(methoxymethyl)benzoic acid, isoochracinic acid, secalonic acid D, and dicerandrol A using mass spectroscopy and nuclear magnetic resonance spectroscopic analyses. Emodin exhibited strong antimicrobial activity, especially against Staphylococcus aureus even when growing on cooked pork, with a minimal inhibitory concentration (MIC) of 6.3 μg/mL. Dimeric tetrahydroxanthones, such as secalonic acid D and dicerandrol A, also exhibited potent activity, with MIC values ranging from 9.5 to 28.5 μg/mL. In summary, P. chrysogenum was isolated as a symbiotic fungus of the beetle A. chinensis for the first time and this strain could generate antibacterial secondary metabolites, which could potently inhibit gram-positive bacteria growth in vitro.

Background: Microglia are an integral part of central nervous system, but our understanding of microglial biology is limited due to the challenges in obtaining and culturing primary human microglia. HMC3 is an important cell line for studying human microglia because it is readily accessible and straightforward to maintain in standard laboratories. Although HMC3 is widely used for microglial research, a robust genetic method has not been described. Here, we report a CRISPR genome editing platform, by the electroporation of Cas9 ribonucleoproteins (Cas9 RNP) and synthetic DNA repair templates, to enable rapid and precise genetic modifications of HMC3. For proof-of-concept demonstrations, we targeted the genes implicated in the regulation of amyloid beta (Aβ) and glioblastoma phagocytosis in microglia. We showed that CRISPR genome editing could enhance the phagocytic activities of HMC3., Methods: We performed CRISPR gene knockout (KO) in HMC3 by the electroporation of pre-assembled Cas9 RNP. Co-introduction of DNA repair templates allowed site-specific knock-in (KI) of an epitope tag, a synthetic promoter and a fluorescent reporter gene. The editing efficiencies were determined genotypically by DNA sequencing and phenotypically by immunofluorescent staining and flow cytometry. The gene-edited HMC3 cells were examined in vitro by fluorescent Aβ and glioblastoma phagocytosis assays., Results: Our platform enabled robust single (>90%) and double (>70%) KO without detectable off-target editing by high throughput DNA sequencing. We also inserted a synthetic SFFV promoter to efficiently upregulate the expression of endogenous CD14 and TREM2 genes associated with microglial phagocytosis. The CRISPR-edited HMC3 showed stable phenotypes and enhanced phagocytosis of fluorescence-labeled Aβ1-42 peptides. Confocal microscopy further confirmed the localization of Aβ 1-42 aggregates in the acidified lysosomes. HMC3 mutants also changed the phagocytic characteristic toward apoptotic glioblastoma cells., Conclusion: CRISPR genome editing by Cas9 RNP electroporation is a robust approach to genetically modify HMC3 for functional studies such as the interrogation of Aβ and tumor phagocytosis, and is readily adoptable to investigate other aspects of microglial biology., 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 © 2023 Chang, Wang and Lin.)

Electrocatalytic reduction of carbon dioxide into value-added chemical fuels is a promising way to achieve carbon neutrality. Bismuth-based materials have been considered as favorable electrocatalysts for converting carbon dioxide to formic acid. Moreover, size-dependent catalysis offers significant advantages in catalyzed heterogeneous chemical processes. However, the size effects of bismuth nanoparticles on formic acid production have not been fully explored. Here, we prepared Bi nanoparticles uniformly supported on porous TiO 2 substrate electrocatalytic materials by in situ segregation of the Bi element from Bi 4 Ti 3 O 12 . The Bi-TiO 2 electrocatalyst with Bi nanoparticles of 2.83 nm displays a Faradaic efficiency of greater than 90% over a wide potential range of 400 mV. Theoretical calculations have also demonstrated subtle electronic structural evolutions induced by the size variations of Bi nanoparticles, where the 2.83 nm Bi nanoparticles display the most active p-band and d-band centers to guarantee high electroactivity toward CO 2 RR.

HLA-A*24:561:02 differs from HLA-A*24:02:01:01 by one nucleotide in exon 3., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lung cancer remains the most chronic form of cancer and the leading cause of cancer mortality in the world. Despite significant improvements in the treatment of lung cancer, the current therapeutic interventions are only partially effective, necessitating the continued search for better, novel alternative treatments. Angiogenesis and cancer stem cells play a central role in the initiation and propagation of cancers. Tumor angiogenesis is triggered by an angiogenic switch when pro-angiogenic factors exceed anti-angiogenic components. Although many anti-angiogenic agents are used in cancer treatment, there are therapeutic limitations with significant side effects. In recent years, cannabinoids have been investigated extensively for their potential anti-neoplastic effects. Our previous findings showed that cannabidiol (CBD) could impede tumor growth in mouse models of melanoma and glioblastoma. Importantly, CBD has been suggested to possess anti-angiogenic activity. In this study, we tested, for the first time, inhalant CBD in the treatment of heterotopic lung cancer and whether such potential effects could reduce cancer stem cell numbers and inhibit tumor angiogenesis. We implanted NCI H1437 human lung cancer cells in nude mice and treated the mice with inhalant CBD or placebo. The outcomes were measured by tumor size and imaging, as well as by immunohistochemistry and flow cytometric analysis for CD44, VEGF, and P-selectin. Our findings showed that CBD decreased tumor growth rate and suppressed expression of CD44 and the angiogenic factors VEGF and P-selectin. These results suggest, for the first time, that inhalant CBD can impede lung cancer growth by suppressing CD44 and angiogenesis., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment. In our study, a novel recombinant human microplasminogen (rhμPlg) was expressed by Pichia pastoris. Molecular docking showed that the binding of rhμPlg with tissue plasminogen activator (t-PA) was similar to plasminogen, suggesting rh μPlg could be activated by t-PA to generate microplasmin (μPlm). Moreover, rhμPlg had higher catalytic activity than plasminogen in amidolytic assays. Complete PVD was found at vitreous posterior pole of 125 μg rhμPlg-treated eyes without morphological change of retina in juvenile rabbits via intraocular injection. Our results demonstrate that rhμPlg has a potential value in the treatment of vitreoretinopathy., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Breast cancer is a significant public health problem globally and prevention strategies have become of great interest as its incidence rises. Exploring the connection between dietary patterns and the reduction of breast cancer risk is considered a promising approach. High levels of fiber, phytochemicals, a good antioxidant profile, and a composition of advantageous fatty acids are characteristics of healthy dietary programs such as the Mediterranean diet. This review summarized and discussed the active compounds that are considered important in preventing breast cancer, including dietary components from recent related reports. These include polyunsaturated fatty acids, fiber, phytochemicals, and alcohol. Although the exact mechanism for preventing breast cancer using these dietary factors is not well understood, the combination of all the elements in a healthy diet plays a role in reducing breast cancer risk. Considering the elevated probability of breast cancer relapse and mortality, it is crucial to investigate the correlation between a nutritious dietary pattern and breast cancer, while identifying bioactive components that have the potential to mitigate the risk of breast cancer incidence.

Background: Both IGF-1R/PI3K/AKT/mTOR and Hippo pathways are crucial for breast cancer stem cells (BCSCs). However, their interplay remains unclear., Methods: Four triple negative breast cancer cell lines derived from CSC of two patient-derived xenografts (PDXs), AS-B145, AS-B145-1R, AS-B244, and AS-B244-1R, were used to elucidate the role of YAP in BCSCs. YAP silenced BCSCs were analyzed by cell proliferation, aldehyde dehydrogenase (ALDH) activity, mammosphere formation, and tumorigenesis. The effects of modulating IGF-1R and IGF-1 on YAP expression and localization were evaluated. The clinical correlation of YAP and IGF-1R signaling with the overall survival (OS) of 7830 breast cancer patients was analyzed by KM plotter., Results: Knockdown of YAP abates the viability and stemness of BCSCs in vitro and tumorigenicity in vivo. Depletion of IGF-1R by shRNA or specific inhibitor decreases YAP expression. In contrast, IGF-1 addition upregulates YAP and enhances its nuclear localization. YAP overexpression increased the mRNA level of IGF-1, but not IGF-1R. Data mining of clinical breast cancer specimens revealed that basal-like breast cancer patients with higher level of IGF-1 and YAP exhibit significantly shorter OS., Conclusions: YAP contributes to stemness features of breast cancer in vitro and in vivo. The expression and localization of YAP was regulated by IGF-1R and YAP expression in turns upregulates IGF-1, but not IGF-1R. Clinically, higher level of YAP and IGF-1 significantly correlated with shorter OS in basal-like breast cancer. Taken together, these findings suggest the clinical relevance of interplay between YAP and IGF-1/IGF-1R pathway in sustaining the properties of BCSCs. Video Abstract., (© 2023. The Author(s).)

Objective: Immune correlate analyses for vaccine trials have been applied to investigate associations of vaccine efficacy and surrogate markers such as vaccine-induced antibodies. However, the role of antibody as a surrogate marker in predicting the outcome can vary by time, and surrogate-outcome confounding may have resulted in bias even in randomized trials. We provide a framework for surrogate marker assessment to address the aforementioned issues., Study Design and Setting: We reanalyzed the vaccine randomized trial for influenza B. We conducted a mediation analysis that enables estimation of vaccine efficacy, mediation effects and proportion of mediation on disease probabilities at various follow-up times. We proposed instrumental variable (IV) analyses with randomized vaccination as an IV accounting for potential unmeasured confounding., Results: The mediation effect of vaccine efficacy by hemagglutination inhibition (HAI) titer was significantly protective at 181 days after vaccination: 63.2% [95% confidence interval, (CI) = (39.9%, 82.0%)], and HAI titer explained 61.1% [95% CI = (36.7%, 96.2%)] of the protective effect of vaccination., Conclusions: Most of vaccine efficacy is mediated by HAI titer, particularly in children 10 years and older. Our contribution is to provide causal analytics for the role of surrogate marker with weaker assumptions regarding surrogate-disease causation., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Electrochemical water oxidation enables the conversion of H 2 O to H 2 O 2 . It holds distinct advantages to the O 2 reduction reaction, which is restricted by the inefficient mass transfer and limited solubility of O 2 in aqueous media. Nonetheless, most reported anodes suffer from high overpotentials (usually >1000 mV) and low selectivity. Electrolysis at high overpotentials often causes serious decomposition of peroxides and leads to declined selectivity. Herein, we report a ZnGa 2 O 4 anode with dual active sites to improve the selectivity and resist the decomposition of peroxides. Its faradaic efficiency reaches 82% at 2.3 V versus RHE for H 2 O 2 generation through both direct (via OH - ) and indirect (via HCO 3 - ) pathways. The percarbonate is the critical species generated through the conversion of bicarbonate at Ga-Ga dual sites. The peroxy bond is stable on the surface of the ZnGa 2 O 4 anode, significantly improving faradaic efficiency., (© 2023. The Author(s).)

Purpose: Metastasis is the end stage of renal cell carcinoma (RCC), and clear cell renal cell carcinoma (ccRCC) is the most common malignant subtype. The hypoxic microenvironment is a common feature in ccRCC and plays an essential role in the regulation of epithelial-mesenchymal transition (EMT). Accumulating evidence manifests that long non-coding RNAs (lncRNAs) participate in RCC tumorigenesis and regulate hypoxia-induced EMT. Here, we identified a lncRNA RP11-367G18.1 induced by hypoxia, that was overexpressed in ccRCC tissues., Methods: A total of 216 specimens, including 149 ccRCC tumor samples and 67 related normal kidney parenchyma tissue samples, were collected. To investigate the biological fucntions of RP11.367G18.1 in ccRCC, migration, invasion, soft agar colony formation, xenograft tumorigenicity assays, and tail vein and orthotopic metastatic mouse models were performed. The relationship between RP11-367G18.1 and downstream signaling was analyzed utilizing reporter assay, RNA pull-down, chromatin immunopreciptation, and chromatin isolation by RNA purification assays., Results: Hypoxic conditions and overexpression of HIF-1α increased the level of RP11-367G18.1. RP11-367G18.1 induced EMT and enhanced cell migration and invasion through variant 2. Inhibition of RP11-367G18.1 variant 2 reversed hypoxia-induced EMT phenotypes. An in vivo study revealed that RP11-367G18.1 variant 2 was required for hypoxia-induced tumor growth and metastasis in ccRCC. Mechanistically, RP11-367G18.1 variant 2 interacted with p300 histone acetyltransferase to regulate lysine 16 acetylation on histone 4 (H4K16Ac), thus contributing to hypoxia-regulated gene expression. Clinically, RP11-367G18.1 variant 2 was upregulated in ccRCC tissues, particularly metastatic ccRCC tissues, and it is linked to poor overall survival., Conclusion: These findings demonstrate the prognostic value and EMT-promoting role of RP11-367G18.1 and indicate that this lncRNA may provide a therapeutic target for ccRCC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Efficient spontaneous molecular oxygen (O 2 ) activation is an important technology in advanced oxidation processes. Its activation under ambient conditions without using solar energy or electricity is a very interesting topic. Low valence copper (LVC) exhibits theoretical ultrahigh activity toward O 2 . However, LVC is difficult to prepare and suffers from poor stability. Here, we first report a novel method for the fabrication of LVC material (P-Cu) via the spontaneous reaction of red phosphorus (P) and Cu 2+ . Red P, a material with excellent electron donating ability and can directly reduce Cu 2+ in solution to LVC via forming Cu-P bonds. With the aid of the Cu-P bond, LVC maintains an electron-rich state and can rapidly activate O 2 to produce ·OH. By using air, the ·OH yield reaches a high value of 423 μmol g -1 h -1 , which is higher than traditional photocatalytic and Fenton-like systems. Moreover, the property of P-Cu is superior to that of classical nano-zero-valent copper. This work first reports the concept of spontaneous formation of LVC and develops a novel avenue for efficient O 2 activation under ambient conditions.

Two-dimensional (2D) transition metal dichalcogenides (TMDs), a rising star in the post-graphene era, are fundamentally and technologically intriguing for photocatalysis. Their extraordinary electronic, optical, and chemical properties endow them as promising materials for effectively harvesting light and catalyzing the redox reaction in photocatalysis. Here, we present a tutorial-style review of the field of 2D TMDs for photocatalysis to educate researchers (especially the new-comers), which begins with a brief introduction of the fundamentals of 2D TMDs and photocatalysis along with the synthesis of this type of material, then look deeply into the merits of 2D TMDs as co-catalysts and active photocatalysts, followed by an overview of the challenges and corresponding strategies of 2D TMDs for photocatalysis, and finally look ahead this topic., (© 2023 Wiley-VCH GmbH.)