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Hsiao-Hui Chen,1 Ja-Liang Lin,1 Wen-Hung Huang,1 Cheng-Hao Weng,1 Shen-Yang Lee,1 Ching-Wei Hsu,1 Kuan-Hsing Chen,1 I-Kuan Wang,2 Chih-Chia Liang,2 Chiz-Tzung Chang,2 Tzung-Hai Yen1 1Department of Nephrology and Division of Clinical Toxicology, Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan; 2Department of Nephrology, China Medical University Hospital and China Medical University, Taichung, Taiwan Background: Data on the spectrum of corrosive injury to the esophagus after paraquat or glyphosate-surfactant ingestion are sparse in the literature and confined to case studies and brief reports. Therefore, this study aimed to examine the clinical features, degrees of esophageal injury, and clinical outcomes after paraquat or glyphosate herbicide ingestion, and sought to determine what association, if any, may exist between these findings. Methods: We performed an observational study on 47 patients with paraquat or glyphosate ingestion who underwent endoscopic evaluation over a period of 11 years (2000–2011). Results: Corrosive esophageal injuries were classified as grade 1 in 14 (glyphosate-surfactant) and three (paraquat), grade 2a in nine (glyphosate-surfactant) and 18 (paraquat), and grade 2b in one (glyphosate-surfactant) and two (paraquat) patients. No patients had grade 0, 3a, or 3b esophageal injuries. Therefore, the severity of corrosive injury was more severe in the paraquat group (P = 0.005). After toxin ingestion, systemic toxicity occurred, with rapid development of systemic complications in many cases. Neurologic complications occurred more frequently in the glyphosate-surfactant group (29.2% versus 0%, P = 0.005), although respiratory failure (4.2% versus 34.8%, P = 0.008), hepatitis (12.5% versus 52.2%, P = 0.004), and renal failure (20.8% versus 52.2%, P = 0.025) developed more frequently in the paraquat group. Patients with glyphosate poisoning had shorter hospital stays than patients with paraquat poisoning (13.3 ± 15.1 days versus 26.8 ± 10.2 days, P = 0.001). Nevertheless, there was no significant difference in mortality rate between the glyphosate-surfactant and paraquat groups (8.3% versus 13.0%, P = 0.601). We ultimately found that patients with grade 2b esophageal injury suffered from a greater incidence of respiratory (100.0% versus 5.9%, P = 0.001) and gastrointestinal (66.7% versus 11.8%, P = 0.034) complications than patients with grade 1 injury, regardless of herbicide type. Conclusion: Paraquat and glyphosate are mild caustic agents that produce esophageal injuries of grades 1, 2a, and 2b only. Our data also suggest a potential relationship between the degree of esophageal injury and systemic complications. Keywords: paraquat, glyphosate-surfactant, poisoning, suicide, esophageal injury

A low-cost highly sensitive optical accelerometer is developed based on the pick-up head of a commercially available DVD. The proposed accelerometer detects the focus error signal (FES) generated by a moving object using a built-in four-quadrant photodiode. The linear range of the FES curve is employed to indicate the displacement of the seismic mass relative to the base of the accelerometer. The acceleration acting on the base is then determined on the basis of the measured displacement. [ABSTRACT FROM AUTHOR]

Terminalia chebula exhibits a high level of antioxidant capacity and is highly valued in medicine and cosmetics. However, its main efficacy and active ingredients related to antioxidant, whitening, and anti-aging are still unclear. In this study, the active site responsible for its cosmetic efficacy was specified by the biological activity-guided method and further characterized by using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS). T. chebula was ultrasonically extracted by five solvents, and 30% ethanol extract was screened out for subsequent purification by 1,1-D-iphenyl-2-picrylhydrazyl radical (DPPH), 2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulphonate) (ABTS), hydroxyl, and superoxide anion free radical scavenging assays. Five elution fractions were obtained by column chromatography on D101 macroporous adsorbent resin eluted by an increased proportion of ethanol. The 30% ethanol elution fraction was specified as the enrichment site of active ingredients showing good antioxidant capacity and potent inhibitory activity against tyrosinase and elastase. A total of 30 compounds were identified by UHPLC-QTOF-MS/MS in the 30% ethanol elution fraction, including 11 gallotannins, 14 ellagitannins, and 5 other compounds, and these compounds may be the key ingredients in cosmetics beneficial for the skin. Such a biological activity-guided method has provided a simple and rapid venue for specifying the components of medicinal herbs responsible for cosmetic efficacy., (© 2024 John Wiley & Sons Ltd.)

Objective: This study provided a quantitative prediction of best-corrected visual acuity (BCVA) for cataract patients using the inverse problem algorithm (IPA) technique earlier proposed by the authors. Methods : To this end, seven risk factors (age, BMI, MAP, IOP, HbA1c, LDL-C, and gender) were linked by a semi-empirical formula by normalizing each factor into a dimensionless range of -1.0 to +1.0. The adopted inverse problem algorithm (IPA) technique was run via a self-developed program in STATISTICA 7.0, featuring a 29-term nonlinear equation considering seven risk factors, cross-interaction between various pairs of factors, and one constant term [7 + (7 × 6)/2 + 1 = 29]. The IPA neglected quadratic, triple, or quadruple factors' cross-interactions. This study used a dataset of 632 cataract patients to attain a reliable BCVA prediction with a variance of 0.929. A verification dataset of 160 patients with similar symptoms was used to verify this approach's feasibility, reaching a good correlation with R 2 = 0.909. Results : The verification group's derived average AT (agreement) (9.12 ± 27.00%) indicated a slight deviation between the theoretical prediction and practical BCVA. The significant factors were age, body mass index (BMI), and intraocular pressure (IOP), whereas mean arterial pressure (MAP), hemoglobin A1c (HbA1c), low-density-lipoprotein cholesterol (LDL-C), and gender insignificantly contributed to BCVA. Conclusions: The proposed approach is instrumental in AI-assisted clinical diagnosis, yielding robust BCVA predictions for individual cataract patients based on their biological indices before the ophthalmological examination procedure.

Objective: To assess the effectiveness of alternating hot-cold water immersion (AHCWI) in patients with acute stroke., Design: A single-blind pilot randomized controlled trial., Setting: Department of Rehabilitation Medicine of a medical center., Participants: Early stroke survivors (N=24) with moderate-to-severe arm paresis., Interventions: In addition to conventional rehabilitation, eligible patients were randomly assigned to an AHCWI group (n=12, for AHCWI) or a control group (n=12, for upper limb [UL] cycling exercises) 5 times per week for 6 weeks., Main Outcome Measures: The Fugl-Meyer Assessment motor-UL (FMA-UL) score, Motricity Index-UL (MI-UL) score, modified Motor Assessment Scale (MMAS; including its UL sections, MMAS-UL) score, Berg Balance Scale score, Barthel Index (BI), and modified Ashworth Scale score were assessed by the same uninvolved physical therapist at baseline and after 4 and 6 weeks of intervention., Results: Compared with the control group, the AHCWI group performed better, with significant group effects (P<.05), and exhibited significant improvements in FMA-UL, MI-UL, and MMAS-UL scores at 4 and 6 weeks (P<.05). Although the remaining outcomes were not significantly different, they favored the AHCWI group. Notably, a significant difference was observed in the BI at 4 weeks (P=.032). Significant changes in the muscle tone or adverse effects were not observed in either group after the intervention., Conclusions: AHCWI with stroke rehabilitation is feasible and may facilitate motor function recovery of the paretic UL after a stroke., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study investigates whether hAFSCs can improve bladder function in partial bladder outlet obstruction (pBOO) rats by targeting specific cellular pathways. Thirty-six female rats were divided into sham and pBOO groups with and without hAFSCs single injection into the bladder wall. Cystometry, inflammation/hypoxia, collagen/fibrosis/gap junction proteins, and smooth muscle myosin/muscarinic receptors were examined at 2 and 6 weeks after pBOO or sham operation. In pBOO bladders, significant increases in peak voiding pressure and residual volume stimulated a significant upregulation of inflammatory and hypoxic factors, TGF-β1 and Smad2/3. Collagen deposition proteins, collagen 1 and 3, were significantly increased, but bladder fibrosis markers, caveolin 1 and 3, were significantly decreased. Gap junction intercellular communication protein, connexin 43, was significantly increased, but the number of caveolae was significantly decreased. Markers for the smooth muscle phenotype, myosin heavy chain 11 and guanylate-dependent protein kinase, as well as M2 muscarinic receptors, were significantly increased in cultured detrusor cells. However, hAFSCs treatment could significantly ameliorate bladder dysfunction by inactivating the TGFβ-Smad signaling pathway, reducing collagen deposition, disrupting gap junctional intercellular communication, and modifying the expressions of smooth muscle myosin and caveolae/caveolin proteins. The results support the potential value of hAFSCs-based treatment of bladder dysfunction in BOO patients.

RAD52 is important for the repair of DNA double-stranded breaks 1,2 , mitotic DNA synthesis 3-5 and alternative telomere length maintenance 6,7 . Central to these functions, RAD52 promotes the annealing of complementary single-stranded DNA (ssDNA) 8,9 and provides an alternative to BRCA2/RAD51-dependent homologous recombination repair 10 . Inactivation of RAD52 in homologous-recombination-deficient BRCA1- or BRCA2-defective cells is synthetically lethal 11,12 , and aberrant expression of RAD52 is associated with poor cancer prognosis 13,14 . As a consequence, RAD52 is an attractive therapeutic target against homologous-recombination-deficient breast, ovarian and prostate cancers 15-17 . Here we describe the structure of RAD52 and define the mechanism of annealing. As reported previously 18-20 , RAD52 forms undecameric (11-subunit) ring structures, but these rings do not represent the active form of the enzyme. Instead, cryo-electron microscopy and biochemical analyses revealed that ssDNA annealing is driven by RAD52 open rings in association with replication protein-A (RPA). Atomic models of the RAD52-ssDNA complex show that ssDNA sits in a positively charged channel around the ring. Annealing is driven by the RAD52 N-terminal domains, whereas the C-terminal regions modulate the open-ring conformation and RPA interaction. RPA associates with RAD52 at the site of ring opening with critical interactions occurring between the RPA-interacting domain of RAD52 and the winged helix domain of RPA2. Our studies provide structural snapshots throughout the annealing process and define the molecular mechanism of ssDNA annealing by the RAD52-RPA complex., (© 2024. The Author(s).)

Microfluidics-based organs-on-a-chip offer a promising method for dynamic and 3-dimensional (3D) cell culture to evaluate the cell behaviors within the biomimetic environment. The purpose of this study was to establish neural network connections in a 3D neural stem cell (NSC)-based system with an interstitial level of flow for simulating the brain microenvironment toward a dynamic amyloid-β (Aβ) induced neuronal toxic model on a chip and to compare the biological effects and neurite dysfunction between static and dynamic systems. The brain-on-a-chip system consisted of an impedance analyzing layer, a structured well with a connected channel, and an interface coating with polypeptide films fabricated with modification based on our previous study. The cytotoxicity and percentage of neuron/astrocyte differentiation were all compared in both static and dynamic brain-on-a-chip systems. Reactive oxygen species production, neuron marker expression and neurotransmitter-acetylcholine release were all compared to evaluate functional neurite losses in both static and dynamic systems with/without Aβ addition. Moreover, real-time impedance recording was used to consecutively monitor the neurite connection/disconnection in both static and dynamic brain-on-a-chip systems. The NSC-based dynamic brain-on-a-chip may enable the application of different neurodegenerative disease in vitro models for pathogenesis studies, drug discovery and novel therapeutic method development.

Background: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning., Methods: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy., Results: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS)., Conclusions: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients., (© 2024. The Author(s).)

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer., Methods: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence., Results: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups., Conclusion: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Acetylcholinesterase (AChE) is an important therapeutic target for the treatment of Alzheimer's disease (AD), and the development of natural AChE inhibitors as candidates has played a significant role in drug discovery. In this study, the inhibition mechanisms of four ellagitannins, punicalagin, chebulinic acid, geraniin and corilagin, from Terminalia chebula fruits on AChE were investigated systematically by a combination of inhibition kinetics, multi-spectroscopic methods and molecular docking. The kinetic results showed that punicalagin, chebulinic acid and geraniin exhibited strong reversible inhibitory effects on AChE in an uncompetitive manner with the IC 50 values of 0.43, 0.50, and 0.51 mM, respectively, while corilagin inhibited AChE activity in a mixed type with the IC 50 value of 0.72 mM. The results of fluorescence and UV-vis spectra and fluorescence resonance energy transfer (FRET) revealed that four ellagitannins could significantly quenched the intrinsic fluorescence of AChE though a static quenching along with non-radiative energy transfer. Thermodynamic analyses showed that values of ΔG, ΔH and ΔS were negative, indicating that all binding processes were spontaneous, and the hydrogen bonding and Van der Waals forces might make a great contribution to the formation of inhibitor-AChE complexes. The synchronous fluorescence, three-dimensional (3D) fluorescence, UV-vis, and FT-IR spectra studies suggested that four ellagitannins could lead to alterations in the micro-environment and secondary structure of AChE, and thus the conformational change of AChE. Moreover, molecular docking demonstrated that four ellagitannins could interacted with main amino acid residues of AChE with affinity energies ranging from -9.9 to -8.7 kJ/mol, and further confirmed the above experimental results. This study provided valuable findings for the potential application of four ellagitannins as promising candidates in the exploration of natural AChE inhibitors for the treatment of AD., 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 B.V.)

This study was to investigate urinary beta 3-adrenoceptor concentration as a biomarker for overactive bladder (OAB) and predictor of treatment outcomes in women receiving the beta 3-adrenoceptor agonist mirabegron. The study comprised 50 women identified with OAB and 35 women considered as healthy controls. All women with OAB received daily dosage of 50 mg of mirabegron for 12 weeks. Bladder diaries, OAB-related questionnaires, and global response assessment scale (GRAS) data were collected. Urinary beta 3-adrenoceptor concentration was measured through enzyme-linked immunosorbent assay. All OAB-related questionnaires and GRAS indicated improved posttreatment urinary health. After mirabegron treatment, the frequency of micturition and urgency episodes decreased, but the urinary beta 3-adrenoceptor/creatinine (Cr) ratio increased. The urinary beta 3-adrenoceptor/creatinine ratio was identified as a sensitive biomarker for OAB with a confidence interval of 0.656 to 0.856 (p < 0.001). A negative correlation (- 0.431, p = 0.040) between this biomarker and health-related quality of life (HRQL) scores. The Beta 3-adrenoceptor/Cr levels increased significantly in the treatment-responsive group, while they remained unchanged in the unsatisfactory outcome group. This study shows that 12 weeks of mirabegron treatment improves OAB symptoms and HRQL. Furthermore, urinary beta 3-adrenoceptor concentration may be a diagnostic biomarker for OAB., (© 2023. The Author(s).)

Background: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The transfer RNA-derived fragments (tRFs) are a new group of small noncoding RNAs, which are dysregulated in many cancers. Until now, the expression and function of tRFs in glioma remain unknown., Methods: The expression profiles of tRF subtypes were analyzed using the Cancer Genome Atlas (TCGA)-low-grade gliomas (LGG)/GBM dataset. The target genes of tRFs were subjected to Gene Ontology, Kyoto Encyclopedia and Gene set enrichment analysis of Genes and Genomes pathway enrichment analysis. The protein-protein interaction enrichment analysis was performed by STRING. QRT-PCR was performed to detect the expressions of tRFs in human glioma cell lines U87, U373, U251, and human astrocyte cell line SVG p12. Western blot assay was used to detect to the expression of S100A11. The interaction between tRF-19-R118LOJX and S100A11 mRNA 3'UTR was detected by dual-luciferase reporter assay. The effects of tRF-19-R118LOJX, tRF-19-6SM83OJX and S100A11 on the glioma cell proliferation, migration and in vitro vasculogenic mimicry formation ability were examined by CCK-8 proliferation assay, EdU assay, HoloMonitor cell migration assay and tube formation assay, respectively., Results: tRF-19-R118LOJX and tRF-19-6SM83OJX are the most differentially expressed tRFs between LGG and GBM groups. The functional enrichment analysis showed that the target genes of tRF-19-R118LOJX and tRF-19-6SM83OJX are enriched in regulating blood vessel development. The upregulated target genes are linked to adverse survival outcomes in glioma patients. tRF-19-R118LOJX and tRF-19-6SM83OJX were identified to suppress glioma cell proliferation, migration, and in vitro vasculogenic mimicry formation. The mechanism of tRF-19-R118LOJX might be related to its function as an RNA silencer by targeting the S100A11 mRNA 3'UTR., Conclusion: tRFs would become novel diagnostic biomarkers and therapeutic targets of glioma, and the mechanism might be related to its post-transcriptionally regulation of gene expression by targeting mRNA 3'UTR., (© 2023. BioMed Central Ltd., part of Springer Nature.)

A [3 + 3] annulation of 3-aryl-3-hydroxyisoindolinones for the efficient synthesis of isoindolinone-derived spiroisochromenes is reported. In this Rh(III)-catalyzed spirocyclization reaction, vinylene carbonate is used as the coupling partner and acts as a three-atom synthon (C-C-O) through the decarboxylation process. This atom-economic reaction worked efficiently under mild conditions via a C-H activation pathway. It is the first example where 3-aryl-3-hydroxyisoindolinones are used as the building blocks to construct spiroheterocycles.

Homologous recombination is a fundamental process of life. It is required for the protection and restart of broken replication forks, the repair of chromosome breaks and the exchange of genetic material during meiosis. Individuals with mutations in key recombination genes, such as BRCA2 (also known as FANCD1), or the RAD51 paralogues RAD51B, RAD51C (also known as FANCO), RAD51D, XRCC2 (also known as FANCU) and XRCC3, are predisposed to breast, ovarian and prostate cancers 1-10 and the cancer-prone syndrome Fanconi anaemia 11-13 . The BRCA2 tumour suppressor protein-the product of BRCA2-is well characterized, but the cellular functions of the RAD51 paralogues remain unclear. Genetic knockouts display growth defects, reduced RAD51 focus formation, spontaneous chromosome abnormalities, sensitivity to PARP inhibitors and replication fork defects 14,15 , but the precise molecular roles of RAD51 paralogues in fork stability, DNA repair and cancer avoidance remain unknown. Here we used cryo-electron microscopy, AlphaFold2 modelling and structural proteomics to determine the structure of the RAD51B-RAD51C-RAD51D-XRCC2 complex (BCDX2), revealing that RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament, whereas RAD51B is highly dynamic. Biochemical and single-molecule analyses showed that BCDX2 stimulates the nucleation and extension of RAD51 filaments-which are essential for recombinational DNA repair-in reactions that depend on the coupled ATPase activities of RAD51B and RAD51C. Our studies demonstrate that BCDX2 orchestrates RAD51 assembly on single stranded DNA for replication fork protection and double strand break repair, in reactions that are critical for tumour avoidance., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

This study investigated the association of de Quervain tenosynovitis (DQT) with subsequent adhesive capsulitis (AC) development. Patients with DQT between 2001 and 2017 from the Taiwan National Health Insurance Research Database were the DQT cohort. The 1:1 propensity score matching method was applied for creating control cohort. The primary outcome was defined as new-onset of AC at least 1 year after the date of confirmed diagnosis of DQT. In total, 32,048 patients with mean age 45.3 years were included. DQT was significantly positively associated with risk of new-onset AC after adjustment for baseline characteristics. Furthermore, severe DQT requiring rehabilitation was positively associated with risk of new-onset AC. In addition, male gender and age under 40 may be additional risk factors for new-onset AC, compared to female gender and age over 40. Cumulative incidence of AC after 17 years was 24.1% among patients with severe DQT requiring rehabilitation and was 20.8% among patients with DQT without rehabilitation. This is the first population-based study to demonstrate an association between DQT and new-onset AC. The findings recommend that preventive occupational therapy, including active modification for the shoulder joint and adjustments to daily activities, may be necessary for patients with DQT to reduce their risk of developing AC.

Introduction: The primary objective of this study is to determine the prevalence of overactive bladder (OAB) and detrusor overactivity (DO) in female patients who were referred for urodynamic study (UDS) because of lower urinary tract symptoms (LUTS). The secondary objective is to determine the subjective and objective differences between female OAB patients with and without DO., Materials and Methods: All female patients who underwent UDS for LUTS between June 2016 and September 2019 were retrospectively reviewed. Personal history, medical history, physical examination, and validated questionnaires were collected. One-hour pad test and multichannel urodynamic study was performed. All statistical analyses were conducted by SAS 9.4. P-value < 0.05 was considered statistically significant., Results: A total of 4184 female patients underwent UDS because of LUTS between June 2016 and September 2019; 1524 patients were analyzed for OAB or DO. The occurrence of OAB was 36.4%. The overall incidence of DO in OAB patients was 15.5%; 9.5% of all patients had DO findings on UDS, and 4.6% were incidental findings. There were significant differences among mean age, parity, ICIQ-UI SF, OABSS, POPDI-6, and all UDS parameters (except for maximal urethral pressure and pressure transmission ratio) between patients with and without DO. In patients with DO, there were no significant differences among age, parity, and BMI with or without OAB symptoms. However, there were significant differences among mean OABSS, ICIQ-UI SF, UDI-6, POPDI-6, IIQ-7, and pad test., Conclusions: Patients with DO are associated with older age, increased parity, greater urine leakage, and worse storage and micturition functions on UDS. Combinations of subjective and objective measurements are better predictive models for OAB patients., (© 2022. The International Urogynecological Association.)

Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody. In human induced pluripotent stem cell (iPSC)-derived microglia, ATV:TREM2 induced proliferation and improved mitochondrial metabolism. Single-cell RNA sequencing and morphometry revealed that ATV:TREM2 shifted microglia to metabolically responsive states, which were distinct from those induced by amyloid pathology. In an AD mouse model, ATV:TREM2 boosted brain microglial activity and glucose metabolism. Thus, ATV:TREM2 represents a promising approach to improve microglial function and treat brain hypometabolism found in patients with AD., (© 2023. The Author(s).)

Our genomes harbor conserved DNA sequences, known as common fragile sites (CFSs), that are difficult to replicate and correspond to regions of genome instability. Following replication stress, CFS loci give rise to breaks or gaps (termed CFS expression) where under-replicated DNA subsequently undergoes mitotic DNA synthesis (MiDAS). We show that loss of the structure-selective endonuclease GEN1 reduces CFS expression, leading to defects in MiDAS, ultrafine anaphase bridge formation, and DNA damage in the ensuing cell cycle due to aberrant chromosome segregation. GEN1 knockout cells also exhibit an elevated frequency of bichromatid constrictions consistent with the presence of unresolved regions of under-replicated DNA. Previously, the role of GEN1 was thought to be restricted to the nucleolytic resolution of recombination intermediates. However, its ability to cleave under-replicated DNA at CFS loci indicates that GEN1 plays a dual role resolving both DNA replication and recombination intermediates before chromosome segregation., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigated the effects of outpatient rehabilitation therapy (RT) on the functional performance of children from Eastern Taiwan with rare or genetic diseases., Materials and Methods: This retrospective observational cohort study included 73 children from Eastern Taiwan who were affected with rare or genetic diseases, with an average age of 8.57 ± 5.33 years (47 boys and 26 girls). Each child received the goal-directed therapy known as outpatient RT, which was delivered by a multidisciplinary team of specialists. To assess the effectiveness of RT, the WeeFIM-C questionnaire data were collected and analyzed., Results: After receiving outpatient RT, most of the children only required low-to-moderate assistance with self-care tasks (4.36 ± 2.38), and they could perform mobility-related activities under supervision or independently (5.70 ± 2.29). Moreover, most only required minimal assistance with tasks related to cognitive functioning and tended to complete such tasks under supervision (4.97 ± 2.05). The functional performance was significantly different among three studied groups, in terms of self-care ( F [2, 68] = 5.42, P < 0.007), mobility ( F [2, 68] = 8.17, P < 0.001), cognitive functioning ( F [2, 68] = 3.31, P < 0.042), and overall ( F [2, 68] = 6.44, P < 0.003) functional performance., Conclusion: The results of this study demonstrated that the functional status was different among three studied groups in terms of self-care, mobility, and cognitive functioning after receiving outpatient RT., Competing Interests: Dr. Shao-Yin Chu, an editorial board members at Tzu Chi Medical Journal, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper., (Copyright: © 2023 Tzu Chi Medical Journal.)

The root lesion nematode, Pratylenchus spp., has a wide host range affecting many economically important crops (Castillo and Vovlas 2007). Cassava (Manihot esculenta Crantz) is an important food crop in several countries, commonly used for the material of bioethanol, animal feed, and starch extraction (Howeler 2014). Soil samples were collected from a mono-cropping cassava farm located in the Houbi district, Tainan city, in Southern Taiwan in October 2021 in a routine soil survey, and there is no obvious above ground symptoms. The cassava is a local cultivar, the sampled tuber did not have lesions, but small brown lesions were present on the roots. Nematodes were extracted using the modified Baermann funnel method (Tsay et al. 2004) for 24 h. Root lesion nematodes were the dominant genera in this sample, containing over 20 individuals per 100 cm3 of soil. Females of the root lesion nematodes were picked, and surface-sterilized with 2000 ppm malachite green for 30 sec and streptomycin for 30 mins. After sterilization, a single female was transferred onto the carrot discs to establish a pure line (Coyne et al. 2014). After 2 months, nematodes were extracted from that pure culture for morphometric, molecular identification, and pathogenicity tests. The female has a moderately slender body, a low and flat lip region, a sclerotized head frame, and a short ventral overlap of the esophagus, monovarial, prodelphic, and post-uterine sac. The tail is conical and the tip is rounded or flattened. The body measures of 20 females were: body length 564.43 μm (511 to 619 μm), stylet length 18.64 μm (18.1 to 19.5 μm), tail length 32.43 μm (27.1 to 38.5 μm), post uterine sac length 12.79 μm (9.41 to 16.9 μm), and V value 85.16% (84.1 to 86.6%). Values of a, b, c, and c' ratios were 22.32 (18.9 to 26.1), 6.11 (5.36 to 6.73), 17.55 (13.8 to 20.5), and 1.18 (0.92 to 1.5), respectively. All morphometric data were similar to the previous description of P. brachyurus (Castillo and Volvlas 2007). DNA was extracted from three nematodes of the pure cultures using Viagen DirectPCR lysis buffer, and used for PCR amplification of the 18S rRNA fragment and the D2-D3 expansion segment of 28S rRNA using primer sets D2A/D3B and 988F/2646R, respectively (Holterman et al. 2006; Subbotin et al. 2006). The sequence of 18S ribosomal RNA (OP020594) shared 99% similarity with the P. brachyurus sequence deposited in the GenBank database (KY424148), and the sequence of 28S rRNA (OP020593) also shared 99% similarity with several P. brachyurus sequences (e.g. KF712473, MG745329). Bayesian consensus trees, constructed from both 18S and 28S sequences revealed that the nematodes collected in this study are clustered together with P. brachyurus sequences from other countries(Subbotin, et al. 2008). Therefore, the nematodes collected from cassava were identified as P. brachyurus based on morphology, molecular data, and phylogenetic relationship. To determine the pathogenicity, three eight-week-old cassava plants (cv. TMS 60444) were planted in 12-cm-diameter pots filled with 600 cm3 of sterile peat moss: sand (1:1, W: W) and inoculated with 50 nematodes containing different stages. Two plants treated with water were used as the mock control. Seventy-five days after inoculation, nematodes in the soil were recovered using the modified Baermann funnel method for 24 h, and the nematodes inside the root were stained with acid fuchsin. The average reproduction factor (final population/initial population) was 3.93, thus confirming cassava as a host of P. brachyurus. P. brachyurus was previously reported on peanuts and bananas in Taiwan, and wasn't a dominant species in the field. Finding this nematode on this cassava farm suggests this nematode might have a wider distribution than expected.

Introduction: Low-energy extracorporeal shock wave therapy (LiESWT) is a new potential treatment for intractable interstitial cystitis/bladder pain syndrome (IC/BPS), and this paper will evaluate its therapeutic effects on IC/BPS., Materials and Methods: This prospective clinical trial enrolled 30 women who have been diagnosed with IC/PBS to receive LiESWT treatment at an intensity of 0.25 mJ/mm 2 and a frequency of 3 pulses/second, for a total of 3000 pulses within 8 weeks. And we assessed questionnaires (including O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI)), 3-day voiding diary, and urodynamic study at the following intervals: 4 weeks of LiESWT (W4), 8 weeks of LiESWT (W8), 1-month follow-up (F1), 3-month follow-up (F3) after LiESWT, and 1 year follow-up (F12)., Results: The primary outcome of questionnaires showed significant improvement of symptoms compared to baseline (W0), especially on ICSI(12.87 ± 3.44 before treatment and 7.87 ± 5.27 at F12, p < 0.05). 3-day voiding diary also revealed significant decrease in daytime voiding frequency (15.57 ± 5.22 times before treatment and 10.70 ± 4.21 times at F1, p < 0.05) and significant increase on average voiding volume (95.85 ± 35.30 mL before treatment and 161.27 ± 74.21 mL at F1, p < 0.05). However, there were no significant differences in all parameters of the urodynamic study., Conclusion: LiESWT can mitigate pain and lower urinary tract symptoms and improve the quality of life in IC/PBS patients, but does not increase the maximal cystometric capacity., (© 2022 Wiley Periodicals LLC.)

Objective: Whilst many studies have explored the mechanisms of stress urinary incontinence (SUI) following various modes of delivery, few have examined outcomes of postpartum SUI in women who experienced new-onset SUI during their pregnancy. Our primary objective was to investigate the risk factors for persistent postpartum SUI in women with new-onset SUI during pregnancy at 1-year follow-up following vaginal delivery., Materials and Methods: 303 women with new-onset SUI during pregnancy who underwent vaginal delivery in a university hospital between 2014 and 2015 were included. In-person interviews were conducted for all participants on the second postpartum day, followed by phone interviews at 12 months postpartum, with completion of structured questionnaires, including Urogenital Distress Inventory Short Form (UDI-6) and Incontinence Impact Questionnaire Short Form (IIQ-7). Demographic, obstetrics and questionnaire scores were analyzed and compared between the group of women who experienced persistent postpartum SUI and the group who did not., Results: At 12 months postpartum, 16.5% (n = 50) of women had persistent postpartum SUI, with 83.5% (n = 253) experiencing resolution of SUI symptoms. Maternal age ≥35 years (aOR = 2.62; 95% CI, 1.40-4.87, P = 0.002), gestational age at birth ≥40 weeks (aOR = 2.21; 95% CI, 1.12-4.37, P = 0.022), and severe perineal lacerations (aOR = 2.32; 95% CI, 1.27-4.45, P = 0.013) were independent risk factors for persistent postpartum SUI for women following vaginal delivery at 1-year follow-up., Conclusion: The prevalence of persistent postpartum SUI at 1-year following vaginal delivery is 16.5%, with advanced maternal age, gestational age at birth ≥40 weeks and severe perineal lacerations being independent risk factors., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Objective: A large-scale multicenter retrospective cohort study was conducted to compare the short- and long-term outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer., Summary of Background Data: RG is being increasingly used worldwide, but data from large-scale multicenter studies on the short- and long-term oncologic outcomes of RG versus LG are limited. The potential benefits of RG compared with LG for gastric cancer remain controversial., Methods: Data from eligible patients who underwent RG or LG for gastric cancer of 11 experienced surgeons from 7 centers in China between March 2010 and October 2019 were collected. The RG group was matched 1:1 with the LG group by using propensity score matching. The primary outcome was postoperative complications., Results: After propensity score matching, a well-balanced cohort of 3552 patients was included for further analysis. The occurrence of overall complications (12.6% vs 15.2%, P = 0.023) was lower in the RG group than in the LG group. RG was associated with less blood loss (126.8 vs 142.5 mL, P < 0.001) and more retrieved lymph nodes in total (32.5 vs 30.7, P < 0.001) and in suprapancreatic areas (13.3 vs 11.6, P < 0.001).The long-term oncological outcomes were comparable between the two groups., Conclusions: The results of this multicenter study demonstrate that RG is a safe and effective treatment for gastric cancer when performed by experienced surgeons, although longer operation time and higher costs are still concerns about RG. This study provides evidence suggesting that RG may represent an alternative surgical treatment to LG., Competing Interests: Conflict of interest Disclosures: The authors declare that they have no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this project was to promote for the family caregivers of stroke patients the resilience evidence translation care model in the community., Introduction: Stroke is the main cause of disability among many patients with chronic diseases. Resilience helps family caregivers facing the consequences of adversity and stress to have a positive outcome., Methods: The study utilized clinical audit strategies under the JBI Practical Application of Clinical Evidence System module. Three audit criteria for the caregivers of stroke patients were considered. A preimplementation audit was conducted with eight nurses and 30 caregivers to measure compliance between current practice and best practice. From that audit we identified barriers and facilitators to practice change by undertaking a Getting Research into Practice analysis. A postimplementation audit was conducted using the same number of samples at 8 weeks for the caregivers to evaluation, and the outcomes using follow-up audit., Results: The three criteria showed an improvement: nurses who received education about resilience care protocols, criterion 1 from 0 to 100%, criterion 2 from 0 to 100%, criterion 3 from 0 to 90%. The results showed that the average resilience of caregivers increased from 17.47 (SD ± 1.94) to 18.33 (SD ± 1.54). The resilience scale of pretest and posttest scores were significantly improved ( P  ≤ 0.001)., Conclusion: The implementation of best practice for enhancing resilience of the family caregivers of stroke patients on the resilience evidence translation care model: a best practice implementation project in community settings is possible. The results indicate that evidence-based practice is an effective method for enhancing the resilience of family caregivers. The strategies contributed to the success of this project, such as scenario simulation education, Objective Structured Clinical Examination, regular weekly audits, and collaboration with project leaders when carrying out caregiver case discussion during clinical practice., (Copyright © 2022 JBI. Unauthorized reproduction of this article is prohibited.)

Developing porous materials to overcome the trade-off between adsorption capacity and selectivity for C 2 H 2 /CO 2 separation remains a challenge. Herein, we report a stable HKUST-1-like MOF (ZJU-50a), featuring large cages decorated with high density of supramolecular binding sites to achieve both high C 2 H 2 storage and selectivity. ZJU-50a exhibits one of the highest C 2 H 2 storage capacity (192 cm 3  g -1 ) and concurrently high C 2 H 2 /CO 2 selectivity (12) at 298 K and 1 bar. Single-crystal X-ray diffraction studies on gas-loaded ZJU-50a crystal unveil that the incorporated supramolecular binding sites can selectively take up C 2 H 2 molecule but not CO 2 to result in both high C 2 H 2 storage and selectivity. Breakthrough experiments validated its separation performance for C 2 H 2 /CO 2 mixtures, providing a high C 2 H 2 recovery capacity of 84.2 L kg -1 with 99.5 % purity. This study suggests a novel strategy of engineering supramolecular binding sites into MOFs to overcome the trade-off for this separation., (© 2022 Wiley-VCH GmbH.)

Three-membered rings (3-rings) are an important structural motif in zeolite chemistry, but their formation remains serendipitous in reticular chemistry when designing zeolitic imidazolate frameworks (ZIFs). Herein, we report a design principle for constructing four new ZIFs, termed ZIF-1001 to -1004, from tetrahedral Zn II centers (T), benzotriazolate (bTZ), and different functionalized benzimidazolates (RbIM) that adopt a new zeolite NPO-type topology built from 3-rings. Two factors were critical for this discovery: i) incorporating the bTZ linker within the structures formed 3-rings due to a ∠(T-bTZ-T) angle of 120-130° reminiscent of the ∠(Ge-O-Ge) angle (130°) observed in germanate zeolite-type structures having 3-rings; and ii) RbIM guided the coordination chemistry of bTZ to bind preferentially in an imidazolate-type mode. This series' ability to selectively capture CO 2 from high-humidity flue gas and trap ethane from tail gas during shale gas extraction was demonstrated., (© 2022 Wiley-VCH GmbH.)

Objective: Due to the COVID-19 pandemic, there is a dramatic drop in in-person residency training due to the implementation of isolation and triage measurements. Here, we propose a new flipped classroom clinical skill training model utilizing a combination of pre-workshop, web-based learning and hands-on workshop that shortens in-person contact time to maintain residency training during the pandemic. Effectiveness of this training model was evaluated with a pre-test and post-test skills competency assessment, two-way feedback, and a five-point Likert scale structured survey questionnaire., Materials and Methods: The workshop was conducted in a flipped classroom fashion by the obstetrics and gynecology (OBGYN) department of a single tertiary teaching medical center covering topics from five OBGYN subspecialities. Every topic consisted of a pre-workshop, web-based, mini lecture (PWML) followed by a hands-on workshop (HW). All first to fourth year OBGYN residents were invited to attend the workshop. All the trainees were required to complete the PWML prior to the day of HW. The workshop consisted of rotational station for each topic and was conducted within one afternoon. A 0-100-point scale pre-test and post-test skills competency evaluation were performed for each station and was assessed by the attending doctor or fellow doctor of each subspeciality. Two-way feedback was done after the post-test evaluation. A five-point Likert scale structured survey instrument consisting of participant's perceptions of the workshop design, relevance to clinical practice, and quality of instructors and materials was created during the curriculum development process and sent to each participant one month after the workshop., Results: A total of 19 residents including five first-year, six second-year, three third-year, and five fourth-year residents completed the entire pre-workshop lecture, workshop, pre-test, and post-test. For all residents, the average post-test score of 5 stations was 95 and was significantly higher than the pre-test score of 60 (p < 0.001). For both junior residents and senior residents, the average post-test scores of 5 stations were also significantly higher than pre-test scores (p < 0.001). Survey generated one month after the workshop showed a high overall satisfaction with the workshop instructors on their professional knowledge, communication skills, and interactions between the instructors and trainees. The average satisfaction scores for manipulation of vaginal breech delivery (VBD), semen analysis (SA), cervical conization (CC), obstetrics anal sphincter injury (OASIS), and laparoscopic suture techniques (LST) were 4.84, 4.96, 4.92, 4.88, and 4.92, respectively The average score for practical application of the training materials, class design and teaching method, overall satisfaction of the session, and time scheduling was 4.84, 4.96, 4.96, and 4.48, respectively. The entire HW was completed within 180 min and was carried out within half a day., Conclusion: With the implementation of isolation and triage measures in the COVID-19 pandemic, there is a dramatic drop in in-person exposure to all aspects of the residency training, in particular, non-emergent surgeries. Utilization of PWML saved 1/3 of in-person time and the entire workshop was completed within 180 min that could be carried out within half a day. The decrease of person-to-person contact time during the COVID-19 pandemic is necessary while still providing curriculum-based residency training in spite of decreased hands-on experience., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Several single-incision mini-slings (SIMSs) have been developed to minimize the potential complications associated with retropubic or transobturator mid-urethral slings. However, few studies compared the efficacy of different types of SIMS. This study compared the outcomes of an adjustable SIMS (Ajust) with a nonadjustable SIMS (Solyx) in the treatment of urodynamic stress incontinence (USI) over postoperative follow-up of 12 months., Materials and Methods: In this study, the surgical outcomes of the first 30 patients receiving Ajust and the first 30 patients undergoing Solyx at a university hospital were reviewed retrospectively, all of whom were diagnosed with USI without coexistent pelvic organ prolapse. Preoperative and postoperative examinations included structured urogynecological questionnaires, 1-hour pad tests, and complete urodynamic testing. Patient demographics, urodynamic parameters, and 12-months surgical outcomes were compared between the Ajust and Solyx groups., Results: There were no significant differences between the Ajust and Solyx groups in terms of subjective cure rate (93.3% vs 90.0%), objective cure rate (89.3% vs 89.3%), and de novo urgency or urge urinary incontinence (13.3% vs 16.7%) 12 months after surgery. Postoperatively, both Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7 scores were significantly improved in the Ajust and Solyx groups. In comparison with preoperative data, postoperative urodynamic results revealed a significant decrease in maximal urethral closure pressure in the Ajust group (n = 28) and a significant increase in residual urine in the Solyx group (n = 28). However, significant differences were not observed in the postoperative pad test and urodynamic data between the Ajust and Solyx groups, and no major complications occurred in either group., Conclusions: In this paper describing the preliminary experience of 30 patients, both adjustable and nonadjustable SIMS performed by an experienced surgeon were safe and effective in correcting USI at 12-month postoperative follow-up., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier B.V.)

The cAMP response element binding protein 1 (CREB1) is an important nuclear transcription factor in eukaryotes. To explore the potential role of CREB1 on Qinchuan bovine skeletal myoblasts, we investigated the function of CREB1 on proliferation and differentiation. In this study, we found that CREB1 promoted cell proliferation by promoting DNA synthesis in S phase and cell division in G2 phase and promoted myogenic differentiation process in bovine myoblasts. Through dual luciferase experiments, we found that CREB1 can bind to the proximal promoter regions of CCNA2 and MyoG, indicating that CREB1 can play a positive regulatory role in the proliferation and differentiation of myoblasts by mediating the transcription of CCNA2 and MyoG. In addition, through downstream target gene analysis and transcriptome sequencing, we found that CREB1 plays a role in cell proliferation, myogenic differentiation, skeletal muscle repair and other related pathways., (Copyright © 2022. Published by Elsevier B.V.)

Topo II and Hsp90 are promising targets. In this study, we first verified the structural similarities between Topo IIα ATPase and Hsp90α N-ATPase. Subsequently, 720 compounds from the Food and Drug Administration (FDA) drug library and kinase library were screened using the malachite green phosphate combination with the Topo II-mediated DNA relaxation and MTT assays. Subsequently, the antimalarial drug quinacrine was found to be a potential dual-target inhibitor of Topo II and Hsp90. Mechanistic studies showed that quinacrine could specifically bind to the Topo IIα ATPase domain and inhibit the activity of Topo IIα ATPase without impacting DNA cleavage. Furthermore, our study revealed that quinacrine could bind Hsp90 N-ATPase and inhibit Hsp90 activity. Significantly, quinacrine has broad antiproliferation activity and remains sensitive to the multidrug-resistant cell line MCF-7/ADR and the atypical drug-resistant tumor cell line HL-60/MX2. Our study identified quinacrine as a potential dual-target inhibitor of Topo II and Hsp90, depending on the ATP-binding domain, positioning it as a hit compound for further structural modification.

Hydrogen-bonded organic frameworks (HOFs) have received tremendous attention in recent years due to the good designability. However, the pure organic nature of HOFs sometimes limits the application development and performance improvement. Functionalizing is an effective strategy to control and modulate material properties, which can achieve properties that cannot be achieved by a pristine material. Herein, a series of HOF-76⊃DSMI were synthesized through functionalizing the stable AIE-based HOF-76 by incorporating a red dye which complements the deficiency of the red component of HOF-76. Then, a single matrix white light-emitting diode (WLED) was fabricated by coating the HOF-76⊃DSMI material on a 460 nm blue LED with CIE chromaticity coordinates of (0.333, 0.329), a correlated colour temperature (CCT) of 5490 K and a colour rendering index (CRI) of 80., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The Community Care Station (CCS) service was initiated by the Taiwanese government as a part of its elderly social services programs. This study aimed to investigate the effects of using an inexpensive exercise toolkit, containing a stick, theraband, sandbag and a small ball, led by a physical therapist among community-dwelling older adults participating in CCS. A total of 90 participants (aged 77.0 ± 6.8 years) were recruited and divided into an intervention group (n = 45) and a comparison group (n = 45). The intervention group regularly participated in a health promotion program with the exercise toolkit for approximately 90 min per twice-weekly session for 3 months, and the comparison group maintained their usual CCS activity program. Both groups were assessed before and after the 3-month intervention period. Outcome measures included the Short Physical Performance Battery (SPPB), one-leg stance, functional reach (FR), Timed Up and Go (TUG), and 10 m walk tests; 83 participants completed the study. No significant between-group differences were found at baseline in general characteristics or outcome variables. After 3 months, the intervention group showed the significant group x time interaction effects in SPPB, one-leg stance, FR, TUG and 10 m walk tests compared to the comparison group (p < 0.05).; A structured group-based health promotion program using a low-cost exercise toolkit could be effective in improving the physical performances, balance, and walking ability of community-dwelling older adults receiving CCS program services. Furthermore, the comparison group maintained most of their physical performances, even showing significant progress on FR.