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Jian-qin Chen,1,&ast; Xue-qing Zhang,1,&ast; Jin-hua Shen,1 Ya-fen Guo,1 Guang-feng Lei,1 Li Tong,1 Hui Wang,1 De-hui Li2 1Department of Nursing, The First People’s Hospital of Changde City, Changde, Hunan Province, People’s Republic of China; 2Department of Infectious Diseases, The First People’s Hospital of Changde City, Changde, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: De-hui Li, Department of Infectious Diseases, The First People’s Hospital of Changde City, 818 Ren min Road, Changde, Hunan Province, People’s Republic of China, Email 161661232@qq.comObjective: Given the immense stress faced by medical staff during the COVID-19 pandemic, this study aimed to evaluate the relationship between mindful attention awareness, fatigue, and perceived symptoms among frontline nurses who performed nucleic acid sample collection during the COVID-19 pandemic, to reduce their fatigue and help them cope with perceived uncomfortable symptoms.Methods: A convenience sampling method was used to survey nurses who travelled to Hainan for nucleic acid sampling in August 2022 using an online (WeChat) questionnaire. A total of 514 frontline nurses who performed nucleic acid tests completed the questionnaire. The questionnaire covered basic demographic information, Mindful Attention Awareness Scale (MAAS) ratings, and Fatigue Severity Scale (FSS) ratings. Spearman correlation analysis was used to separate the relationship between MASS and FSS, and univariate and multivariate factor analyses were used to explore the relevant influences contributing to the occurrence of fatigue.Results: A total of 514 individuals completed the survey,93.97% (n=483) were female, mean age was 31.15 ± 5.7, MASS score was 69.01 ± 13.53, and 296 (57.59%) nurses experienced symptoms of fatigue during the auxiliary period. Spearman correlation analysis showed that FSS was associated with MASS. Multifactorial analysis showed that sex, age, marital status, fertility status, years of work, adaptation to dietary habits, hidrorrhea, and MAAS scores affected the presence of fatigue symptoms among the medical staff in Hainan (P< 0.05).Conclusion: The psychological status of frontline nurses undergoing nucleic acid testing during the pandemic was poor, and the appearance of fatigue symptoms could be effectively reduced by increasing levels of positive thinking among medical staff to help them cope with public health emergencies.Keywords: COVID-19, nucleic acid testing, nurses, mindfulness, fatigue, perceived symptoms

A palladium-catalyzed regioselective [8 + 3] cycloaddition of tropsulfimides and tropones with vinylidenecyclopropane-diesters (VDCP-diesters) has been disclosed in this paper, affording decahydro-1 H -cyclohepta[ b ]pyridine derivatives bearing an allene moiety or decahydro-1 H -cyclohepta[ b ]pyran derivatives having a conjugated diene unit in moderate to good yields. The reactions proceed through a zwitterionic allenyl palladium species derived from VDCP-diesters. The substrate scopes have been investigated and the plausible reaction mechanisms have also been proposed according to the previous work, the first captured zwitterionic Pd-allenyl intermediate, and control experiments.

Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy., (© 2024. The Author(s).)

Mesona chinensis Benth (MCB) is the source of the most commonly consumed herbal beverage in Southeast Asia and China and is thus an economically important agricultural plant. Therefore, optimal extraction and production procedures have significant commercial value. Currently, in terms of green chemistry, researchers are investigating the use of greener solvents and innovative extraction techniques to increase extract yields. This study represents the first investigation of the optimal conditions for ultrasound-assisted deep eutectic solvent (DES) extraction from MCB. The major factors influencing ultrasound-assisted DESs were optimized using the response surface methodcentral-genetic algorithm-back propagation neural networks. This model demonstrated superior predictability and accuracy compared to the RSM model. Various types of DESs were used for the extraction of MCB constituents, with choline chloride-ethylene glycol resulting in the highest yield. The optimal conditions for maximal extraction were the use of choline chloride-ethylene glycol (1:4) as the solvent with a 40% water content, an extraction duration of 60 min at 60°C, and maintaining a leaf-to-solvent ratio of 20 mL/g. Noticeable enhancements in Van der Waals forces and more robust interactions between DESs and the target chemicals were observed relative to those seen with ethanol (70%, v/v) or water. This investigation not only introduced an environmentally friendly approach for highly efficient extraction from MCB but also identified the mechanisms underlying the improved extraction efficacy. These findings have the potential to contribute to the broader utilization of MCB and provide valuable insights into the extraction mechanisms utilizing deep eutectic solvents. PRACTICAL APPLICATION: This work describes an efficient and green ultrasound-assisted deep eutectic solvent (DES) method for Mesona chinensis Benth (MCB) extraction. Molecular dynamics was used to examine the intermolecular interactions between the solvent and the extracted compounds. It is anticipated that green and environmentally friendly solvents, such as DESs, will be used in further research on foods and their bioactive components. With the development of the herbal tea industry, new products made of MCB are becoming increasingly popular, thus gradually making it a research hotspot., (© 2024 Institute of Food Technologists.)

Meningeal lymphatic vessels (MLVs) have crucial roles in removing metabolic waste and toxic proteins from the brain and transporting them to the periphery. Aged mice show impaired meningeal lymphatic function. Nevertheless, as the disease progresses, and significant pathological changes manifest in the brain, treating the condition becomes increasingly challenging. Therefore, investigating the alterations in the structure and function of MLVs in the early stages of aging is critical for preventing age-related central nervous system degenerative diseases. We detected the structure and function of MLVs in young, middle-aged, and aged mice. Middle-aged mice, compared with young and aged mice, showed enhanced meningeal lymphatic function along with MLV expansion and performed better in the Y maze test. Moreover, age-related changes in meningeal lymphatic function were closely associated with vascular endothelial growth factor-C (VEGF-C) expression in the brain cortex. Our data suggested that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction, thus providing a new strategy for preventing age-related central nervous system diseases., 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 B.V. All rights reserved.)

Currently, the drugs used in clinical to treat psoriasis mainly broadly suppress cellular immunity. However, these drugs can only provide temporary and partial symptom relief, they do not cure the condition and may lead to recurrence or even serious toxic side effects. In this study, we describe the discovery of a novel potent CDK8 inhibitor as a treatment for psoriasis. Through structure-based design, compound 46 was identified as the most promising candidate, exhibiting a strong inhibitory effect on CDK8 (IC 50 value of 57 nM) along with favourable inhibition against NF-κB. Additionally, it demonstrated a positive effect in an in vitro psoriasis model induced by TNF-α. Furthermore, this compound enhanced the thermal stability of CDK8 and exerted evident effects on the biological function of CDK8, and it had favourable selectivity across the CDK family and tyrosine kinase. This compound showed no obvious inhibitory effect on CYP450 enzyme. Further studies confirmed that compound 46 exhibited therapeutic effect on IMQ-induced psoriasis, alleviated the inflammatory response in mice, and enhanced the expression of Foxp3 and IL-10 in the dorsal skin in vivo. This discovery provides a new strategy for developing selective CDK8 inhibitors with anti-inflammatory activity for the treatment of psoriasis., Competing Interests: Declaration of Competing Interest All authors have contributed to the work, have read the manuscript and have agreed to be listed as authors. The submitted manuscript has not been published elsewhere and nor is it currently under review by another publication. No potential conflict of interest relevant to this article., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Surgical scheduling is pivotal in managing daily surgical sequences, impacting patient experience and hospital resources significantly. With operating rooms costing approximately US $36 per minute, efficient scheduling is vital. However, global practices in surgical scheduling vary, largely due to challenges in predicting individual surgeon times for diverse patient conditions. Inspired by the Toyota Production System's efficiency in addressing similar logistical challenges, we applied its principles as detailed in the book "Lean Thinking" by Womack and Jones, which identifies processes that do not meet customer needs as wasteful. This insight is critical in health care, where waste can compromise patient safety and medical quality., Objective: This study aims to use lean thinking and Toyota methods to develop a more efficient surgical scheduling system that better aligns with user needs without additional financial burdens., Methods: We implemented the 5 principles of the Toyota system: specifying value, identifying the value stream, enabling flow, establishing pull, and pursuing perfection. Value was defined in terms of meeting the customer's needs, which in this context involved developing a responsive and efficient scheduling system. Our approach included 2 subsystems: one handling presurgery patient data and another for intraoperative and postoperative data. We identified inefficiencies in the presurgery data subsystem and responded by creating a comprehensive value stream map of the surgical process. We developed 2 Excel (Microsoft Corporation) macros using Visual Basic for Applications. The first calculated average surgery times from intra- or postoperative historic data, while the second estimated surgery durations and generated concise, visually engaging scheduling reports from presurgery data. We assessed the effectiveness of the new system by comparing task completion times and user satisfaction between the old and new systems., Results: The implementation of the revised scheduling system significantly reduced the overall scheduling time from 301 seconds to 261 seconds (P=.02), with significant time reductions in the revised process from 99 seconds to 62 seconds (P<.001). Despite these improvements, approximately 21% of nurses preferred the older system for its familiarity. The new system protects patient data privacy and streamlines schedule dissemination through a secure LINE group (LY Corp), ensuring seamless flow. The design of the system allows for real-time updates and has been effectively monitoring surgical durations daily for over 3 years. The "pull" principle was demonstrated when an unplanned software issue prompted immediate, user-led troubleshooting, enhancing system reliability. Continuous improvement efforts are ongoing, except for the preoperative patient confirmation step, which requires further enhancement to ensure optimal patient safety., Conclusions: Lean principles and Toyota's methods, combined with computer programming, can revitalize surgical scheduling processes. They offer effective solutions for surgical scheduling challenges and enable the creation of a novel surgical scheduling system without incurring additional costs., (©Chien-Chung Lin, Jian-Hong Shen, Shu-Fang Chen, Hung-Ming Chen, Hung-Meng Huang. Originally published in JMIR Formative Research (https://formative.jmir.org), 24.05.2024.)

We investigated the relationship among red cell distribution width (RDW), to total serum calcium (TSC) ratio (RCR), and in-hospital mortality in patients with acute ischemic stroke (AIS). This study was a retrospective analysis. The data of 2700 AIS patients was retrospectively analyzed from the Medical Information Mart for Intensive Care database (version IV). The main outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether RCR was independently associated with in-hospital mortality. The Kaplan-Meier method was used to plot the survival curves for RCR. Subgroup analyses were performed to measure the mortality across various subgroups. The area under curve (AUC) of receiver operating characteristic curve (ROC) was calculated to ascertain the quality of RCR as a predictor of in-hospital mortality in patients with AIS. In the multivariate analysis, statistically significant differences were identified in age, ethnicity, length of ICU stay, mechanical ventilation, sequential organ failure assessment (SOFA) score, RDW, hemoglobin, RCR, whether taking anticoagulants, hyperlipidemia, and atrial fibrillation (P < .05). A threshold inflection point value of 1.83 was obtained through a two-piecewise regression model. There was a non-linear relationship between RCR and hospital mortality in patients with AIS. The hazard ratio (HR) and the 95% confidence intervals (CI) on the right and left of the inflection point were 0.93 (0.57-1.51; P = .7660) and 2.96 (1.37-6.42; P = .0060), respectively. The Kaplan-Meier curve indicated that survival rates were higher when RCR was ≤ 1.83 and lower when RDW was > 1.83 after adjustment for age, gender, BMI, ethnicity. The area under curve (AUC) of RCR was 0.715. A higher RCR was associated with an increased risk of in-hospital mortality in patients with AIS., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Changes in an individual's digestive system, hormones, senses of smell and taste, and energy requirement accompanying aging could lead to impaired appetite, but older adults may not notice their risk of nutrient deficiency. When assessing the dietary intake of older adults, it was found that they had more difficulties with short-term recall and open-ended recall and would experience greater fatigue and frustration when compared to younger individuals when completing a lengthy questionnaire. There is a need to develop a brief dietary assessment tool to examine the nutritional needs of older adults. In this study, we aimed to assess the diet of Hong Kong older adults using the short FFQ and examine its reproducibility and relative validity as a dietary assessment tool. Dietary data of 198 older adults were collected via FFQs and three-day dietary records. Correlation analyses, cross-tabulation, one-sample t -tests, and linear regression analyses were used to evaluate the relative validity of the short FFQ. In general, the short FFQ was accurate in assessing the intake of phosphorus, water, grains, and wine, as shown by a significant correlation (>0.7) between values reported in the FFQs and dietary records; good agreement (more than 50% of observations belonged to the same quartile) and insignificant differences detected with the one-sample t -tests and linear regression analyses were observed for the above four variables. Additionally, the intake of proteins, carbohydrates, total fat, magnesium, and eggs in terms of the values reported in the FFQs and dietary records showed good agreement.

The phytochemical study of the fruits of Melia azedarach (Meliaceae) led to the isolation and characterisation of two novel natural limonoids1-deoxy- 3, 20-dicinnamoyl-11-methoxy-meliacarpinin ( 1 ) and 12 β - O- methyl nimbolinin A ( 2 ), along with twelve known limonoids. Its structure was identified by 1D- and 2D-NMR, HR-ESI-MS and comparison with published data. The anti-inflammatory effect of the compounds was measured in vitro in RAW 264.7 cells by evaluating the production of NO stimulated by LPS. Compounds 1, 8 and 14 indicated significant anti-inflammatory effect with inhibition rate of 11.76, 8.45 and 6.59 μM, respectively. Limonoid 1 significantly inhibited the production of NO, TNF- α and IL-1 β in RAW 264.7 cells. Therefore, limonoid derivative may be a promising source of bioactive metabolite for inflammatory diseases.

Handheld optical coherence tomography (HH-OCT) is gaining popularity for diagnosing retinal diseases in neonates (e.g. retinopathy of prematurity). Diagnosis accuracy is degraded by hand tremor and patient motion when using commercially available handheld retinal OCT probes. This work presents a low-cost arm designed to address ergonomic challenges of holding a commercial OCT probe and alleviating hand tremor. Experiments with a phantom eye show enhanced geometric uniformity and volumetric accuracy when obtaining OCT scans with our device compared to handheld imaging approaches. An in-vivo porcine volumetric image was also obtained with the mechanical arm demonstrating clinical deployability., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

Background: To evaluate the possible topographic and surgical risk factors for high postoperative residual astigmatism in patients who undergo small-incision lenticule extraction (SMILE) surgery and have different myopia degrees., Methods: A retrospective cohort study was conducted, and patients who underwent SMILE surgery were enrolled. A total of 80 and 150 eyes from 40 to 75 individuals, respectively, were selected as the low myopia and high myopia groups. The demographic data, visual acuity, refraction, topographic parameters and surgical settings were recorded. Multiple linear regression with interaction tests were performed to survey the risk factors for high postoperative residual astigmatism in each group., Results: Five (6.25%) and 9 (6.00%) eyes presented with high postoperative residual astigmatism in the low myopia and high myopia groups, respectively, but these differences were not significant (P = 0.569). A steep corneal curvature was correlated with a greater risk of high postoperative residual astigmatism in the low myopia group (P = 0.015), while a higher degree of cycloplegic cylinder power, steeper corneal curvature, greater topographic cylinder power, smaller optic zone and longer incision length were associated with a high rate of postoperative residual astigmatism in the high myopia group (all P < 0.05). In addition, the interaction effects of cycloplegic and topographic cylinder power and longer incision length on the incidence of high postoperative residual astigmatism development were more evident in the high myopia group than in the low myopia group (all P < 0.05)., Conclusions: A steep corneal curvature correlates with a high risk of high postoperative residual astigmatism after SMILE surgery, and a higher degree of cycloplegic and topographic cylinder and longer incision are associated with high postoperative residual astigmatism in individuals with high myopia., (© 2024. The Author(s).)

Background: A pay-for-performance plan for rapid antiretroviral therapy (ART) commencement was initiated in 2018, while a modified testing algorithm offers immunochromatographic test (ICT) to replace Western blot (WB), and simultaneous testing with ICT and Nucleic Acid Amplification Test (NAAT) for HIV-positive sera was adopted in 2019 in Taiwan., Methods: Serum specimens collected from 1117 suspected or confirmed HIV infection cases in 2016-2019 were reassessed the performance of WB, ICT, and NAAT. We reviewed the medical records of 10,732 individuals diagnosed with HIV in 2015-2021 to determine the time from screening to confirmatory diagnosis, followed by ART commencement., Results: All 860 WB-positives were also positive by ICT and NAAT. The positive detection percentages were 37.0% by ICT and 51.4% by NAAT for 257 WB-indeterminate and -negative sera. The sensitivity for WB and ICT was 93.8% and 95.5%, respectively. In the people living with HIV (PLHIV) cohort, the median time from initial positive to confirmatory diagnosis decreased from 5 to 6 days before 2019 to 1 day in 2021. The median time from initial positive to ART initiation decreased from 37 days in 2015, 14 days in 2018, to 6 days in 2021. Compared to 2015-2017, the time to ART initiation was 91.48 days lower in 2018 (P < 0.001) and 100.66 days lower in 2019-2021 (P < 0.001) by the adjusted linear regression model., Conclusion: A significant decrease in the time to ART initiation was observed after initiation of the pay-for-performance program and optimized testing algorithm in Taiwan., 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.)

Heart failure (HF) severely impairs human health because of its high incidence and mortality. Cardiac hypertrophy is the main cause of HF, while its underlying mechanism is not fully clear. As an E3 ubiquitin ligase, Ring finger protein 13 (RNF13) plays a crucial role in many disorders, such as liver immune, neurological disease and tumorigenesis, whereas the function of RNF13 in cardiac hypertrophy remains largely unknown. In the present study, we found that the protein expression of RNF13 is up-regulated in the transverse aortic constriction (TAC)-induced murine hypertrophic hearts and phenylephrine (PE)-induced cardiomyocyte hypertrophy. Functional investigations indicated that RNF13 global knockout mice accelerates the degree of TAC-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis and heart dysfunction. On the contrary, adeno-associated virus 9 (AAV9) mediated-RNF13 overexpression mice alleviated cardiac hypertrophy. Furthermore, we demonstrated that adenoviral RNF13 attenuates the PE-induced cardiomyocyte hypertrophy and down-regulates the expression of cardiac hypertrophic markers, while the opposite results were observed in the RNF13 knockdown group. The RNA-sequence of RNF13 knockout and wild type mice showed that RNF13 deficiency activates oxidative stress after TAC surgery. In terms of the mechanism, we found that RNF13 directly interacted with p62 and promoted the activation of downstream NRF2/HO-1 signaling. Finally, we proved that p62 knockdown can reverse the effect of RNF13 in cardiac hypertrophy. In conclusion, RNF13 protects against the cardiac hypertrophy via p62-NRF2 axis., Competing Interests: Declaration of competing interest The manuscript has not been published or submitted for publication elsewhere. All of the authors participated in the study and have agreed to the content of the manuscript and declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

M7G modification, known as one of the common post-transcriptional modifications of RNA, is present in many different types of RNAs. With the accurate identification of m7G modifications within RNAs, their functional roles in the regulation of gene expression and different physiological functions have been revealed. In addition, there is growing evidence that m7G modifications are crucial in the emergence of cancer. Here, we review the most recent findings regarding the detection techniques, distribution, biological functions and Regulators of m7G. We also summarize the connections between m7G modifications and cancer development, drug resistance, and tumor microenvironment as well as we discuss the research's future directions and trends., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Excessive apoptosis of intestinal epithelial cell (IEC) is a crucial cause of disrupted epithelium homeostasis, leading to the pathogenesis of ulcerative colitis (UC). The regulation of Takeda G protein-coupled receptor-5 (TGR5) in IEC apoptosis and the underlying molecular mechanisms remained unclear, and the direct evidence from selective TGR5 agonists for the treatment of UC is also lacking. Here, we synthesized a potent and selective TGR5 agonist OM8 with high distribution in intestinal tract and investigated its effect on IEC apoptosis and UC treatment. We showed that OM8 potently activated hTGR5 and mTGR5 with EC 50 values of 202 ± 55 nM and 74 ± 17 nM, respectively. After oral administration, a large amount of OM8 was maintained in intestinal tract with very low absorption into the blood. In DSS-induced colitis mice, oral administration of OM8 alleviated colitis symptoms, pathological changes and impaired tight junction proteins expression. In addition to enhancing intestinal stem cell (ISC) proliferation and differentiation, OM8 administration significantly reduced the rate of apoptotic cells in colonic epithelium in colitis mice. The direct inhibition by OM8 on IEC apoptosis was further demonstrated in HT-29 and Caco-2 cells in vitro. In HT-29 cells, we demonstrated that silencing TGR5, inhibition of adenylate cyclase or protein kinase A (PKA) all blocked the suppression of JNK phosphorylation induced by OM8, thus abolished its antagonizing effect against TNF-α induced apoptosis, suggesting that the inhibition by OM8 on IEC apoptosis was mediated via activation of TGR5 and cAMP/PKA signaling pathway. Further studies showed that OM8 upregulated cellular FLICE-inhibitory protein (c-FLIP) expression in a TGR5-dependent manner in HT-29 cells. Knockdown of c-FLIP blocked the inhibition by OM8 on TNF-α induced JNK phosphorylation and apoptosis, suggesting that c-FLIP was indispensable for the suppression of OM8 on IEC apoptosis induced by OM8. In conclusion, our study demonstrated a new mechanism of TGR5 agonist on inhibiting IEC apoptosis via cAMP/PKA/c-FLIP/JNK signaling pathway in vitro, and highlighted the value of TGR5 agonist as a novel therapeutic strategy for the treatment of UC., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

In recent years, the strategy of merging visible light photocatalysis and organocatalysis has been utilized and applied in a wide range of reactions. Taking advantage of synergistic visible light photocatalysis with organocatalysis, remarkable progress has recently been achieved in modern chemical synthesis. In these dual catalytic systems, photocatalysts or photosensitizers absorb visible light to induce their photo-excited states which can activate unreactive substrates via electron or energy transfer mechanisms, and organocatalysts are usually employed to control the chemical reactivities of the other substrates. This review mainly focuses on the recent development of cooperative catalysis by the combination of organocatalysis and photocatalysis in recent organic synthesis., (© 2023 Wiley-VCH GmbH.)

Promotion of hepatic glycogen synthesis and inhibition of hepatic glucose production are effective strategies for controlling hyperglycemia in type 2 diabetes mellitus (T2DM), but agents with both properties were limited. Herein we report coronarin A, a natural compound isolated from rhizomes of Hedychium gardnerianum, which simultaneously stimulates glycogen synthesis and suppresses gluconeogenesis in rat primary hepatocytes. We showed that coronarin A (3, 10 μM) dose-dependently stimulated glycogen synthesis accompanied by increased Akt and GSK3β phosphorylation in rat primary hepatocytes. Pretreatment with Akt inhibitor MK-2206 (2 μM) or PI3K inhibitor LY294002 (10 μM) blocked coronarin A-induced glycogen synthesis. Meanwhile, coronarin A (10 μM) significantly suppressed gluconeogenesis accompanied by increased phosphorylation of MEK, ERK1/2, β-catenin and increased the gene expression of TCF7L2 in rat primary hepatocytes. Pretreatment with β-catenin inhibitor IWR-1-endo (10 μM) or ERK inhibitor SCH772984 (1 μM) abolished the coronarin A-suppressed gluconeogenesis. More importantly, we revealed that coronarin A activated PI3K/Akt/GSK3β and ERK/Wnt/β-catenin signaling via regulation of a key upstream molecule IRS1. Coronarin A (10, 30 μM) decreased the phosphorylation of mTOR and S6K1, the downstream target of mTORC1, which further inhibited the serine phosphorylation of IRS1, and subsequently increased the tyrosine phosphorylation of IRS1. In type 2 diabetic ob/ob mice, chronic administration of coronarin A significantly reduced the non-fasting and fasting blood glucose levels and improved glucose tolerance, accompanied by the inhibited hepatic mTOR/S6K1 signaling and activated IRS1 along with enhanced PI3K/Akt/GSK3β and ERK/Wnt/β-catenin pathways. These results demonstrate the anti-hyperglycemic effect of coronarin A with a novel mechanism by inhibiting mTORC1/S6K1 to increase IRS1 activity, and highlighted coronarin A as a valuable lead compound for the treatment of T2DM., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Frailty can change the prognosis and treatment approach of chronic diseases. We, therefore, conducted this study to explore the relationship between frailty syndrome and blood pressure variability in the elderly. The clinical data of 150 elderly patients with debilitating syndrome admitted to the neurology department of our hospital from May 2021 to May 2022 were selected, and they were grouped according to Fried debilitation scale and divided into 50 cases each in the debilitation group, pre-debilitation group, and no-debilitation group. The general data, co-morbidities, medications, and biochemical indexes were collected. The 24-hour ambulatory blood pressure monitoring was performed in each group, and the mean systolic blood pressure, diastolic blood pressure, nocturnal systolic load value, and diastolic load value were analyzed to determine the relationship between blood pressure variability and senile frailty. Serum albumin (ALB) and high-density lipoprotein were significantly lower in the debilitated and pre-debilitated groups than in the non-debilitated group (P < .05). Multivariate logistic regression analysis revealed that age (odds ratio [OR]: 3.910, 95% confidence intervals [CI]: 2.021-5.402) was a risk factor for frailty in the elderly, and serum ALB (OR: 0.656, 95% CI: 0.110-0.960) and HDL (OR: 0.581, 95% CI: 0.237-0.944) were protective factors for frailty in the elderly. Age, type of medication taken, co-morbidities, serum ALB, and HDL are influencing factors of debilitating syndrome. Serum ALB and HDL are protective factors against debilitating syndrome in the elderly. Age is an independent risk factor of debilitation in the elderly and increased fluctuation of blood pressure in the elderly can increase their risk of developing debilitating syndrome., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

An asymmetric linear selective allylic alkylation of vinylaziridines with 3-aryl oxindoles has been developed by using a chiral oxamide-phosphine (COAP-Bn-OMe- p )/palladium complex in methanol, which furnished a wide variety of 3,3-disubstituted oxindole derivatives in good yields with excellent regio- and enantioselectivities.

Background: Radiation resistance is a challenge that limits the therapeutic benefit of colorectal cancer (CRC) treatment, but the mechanism underlying CRC radiation resistance remains unclear. Andrographolide shows a broad-spectrum anti-tumor effect in various malignancies, including CRC, its effect and how it functions in CRC initiation, and radiation have not been established. This study aimed to explore the mechanism of CRC radiation resistance and the potential mechanisms of andrographolide on CRC radiation., Methods: Two acquired radioresistant cell lines were established and high throughput sequencing was employed to screen out the differentially expressed genes. The expression of AZGP1, which was upregulated in the acquired radioresistant tissues, was verified by microarray data recomputing. The common targets of andrographolide, CRC initiation, and radiation resistance were obtained, and the corresponding functional enrichment and pathway analysis were performed. The interaction between AZGP1 and andrographolide was investigated using molecular docking., Results: AZGP1 was upregulated in both the radioresistant cell model and microarray data. Moreover, AZGP1 was upregulated in cancerous colorectal tissue and displayed a tendency toward elevated expression in patients with an unfavorable prognosis. AZGP1 was identified as the common target of andrographolide, colorectal cancer initiation, and radiotherapy resistance. Ultimately, the protein structure of AZGP1 proved to be closely intertwined with the crystal texture of andrographolide., Conclusion: AZGP1 is recognized as a crucial factor for both CRC initiation and radioresistance. Andrographolide may affect the radioresistance of CRC via the targeting of AZGP1. Thus, the combination of andrographolide and AZGP1 intervention might be a promising strategy for improving the treatment benefit of CRC radiotherapy., Competing Interests: The authors declare that they have no conflicts of interest., (© 2022 Fang et al.)

Background: Disordered lipid metabolism plays an essential role in both the initiation and progression of alcoholic fatty liver disease (AFLD), and fatty acid β-oxidation is increasingly considered as a crucial factor for controlling lipid metabolism. Hif-2α is a member of the Hif family of nuclear receptors, which take part in regulating hepatic fatty acid β-oxidation. However, its functional role in AFLD and the underlying mechanisms remain unclear., Results: Hif-2α was upregulated in EtOH-fed mice and EtOH-treated AML-12 cells. Inhibition or silencing of Hif-2α led to increased fatty acid β-oxidation and BNIP3-dependent mitophagy. Downregulation of Hif-2α activates the PPAR-α/PGC-1α signaling pathway, which is involved in hepatic fatty acid β-oxidation, by mediating BNIP3-dependent mitophagy, ultimately delaying the progression of AFLD., Conclusions: Hif-2α induces liver steatosis, which promotes the progression of AFLD. Here, we have described a novel Hif-2α-BNIP3-dependent mitophagy regulatory pathway interconnected with EtOH-induced lipid accumulation, which could be a potential therapeutic target for the prevention and treatment of AFLD., (© 2022. The Author(s).)

Background: Very few studies have been published on the causes of death of upper tract urothelial carcinoma (UTUC). We sought to explore the mortality patterns of contemporary UTUC survivors., Methods: We performed a retrospective cohort study involving patients with upper urinary tract carcinoma from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database (2000 and 2015). We used standardized mortality ratios (SMRs) to compare death rates among patients with UTUC in the general population and excess absolute risks (EARs) to quantify the disease-specific death burden., Results: A total of 10,179 patients with UTUC, including 7,133 who died, were included in our study. In total, 302 (17.17%) patients with the localized disease died of UTUC; however, patients who died from other causes were 4.8 times more likely to die from UTUC (n = 1,457 [82.83%]). Cardiovascular disease was the most common non-cancer cause of death (n = 393 [22.34% of all deaths]); SMR, 1.22; 95% confidence intervals [CI], 1.1-1.35; EAR, 35.96). A total of 4,046 (69.99%) patients with regional stage died within their follow-up, 1,413 (34.92%) of whom died from UTUC and 1,082 (26.74%) of whom died from non-cancer causes. UTUC was the main cause of death (SMR, 242.48; 95% CI, 230-255.47; EAR, 542.47), followed by non-tumor causes (SMR, 1.18; 95% CI, 1.11-1.25; EAR, 63.74). Most patients (94.94%) with distant stage died within 3 years of initial diagnosis. Although UTUC was the leading cause of death (n = 721 [54.29%]), these patients also had a higher risk of death from non-cancer than the general population (SMR, 2.08; 95% CI, 1.67-2.56; EAR, 288.26)., Conclusions: Non-UTUC deaths accounted for 82.48% of UTUC survivors among those with localized disease. Patients with regional/distant stages were most likely to die of UTUC; however, there is an increased risk of dying from non-cancer causes that cannot be ignored. These data provide the latest and most comprehensive assessment of the causes of death in patients with UTUC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peng, Wu, Zhang, Shen, Yu and Mao.)

Measurement error is non-negligible and crucial in SHM data analysis. In many applications of SHM, measurement errors are statistically correlated in space and/or in time for data from sensor networks. Existing works solely consider spatial correlation for measurement error. When both spatial and temporal correlation are considered simultaneously, the existing works collapse, as they do not possess a suitable form describing spatially and temporally correlated measurement error. In order to tackle this burden, this paper generalizes the form of correlated measurement error from spatial correlation only or temporal correlation only to spatial-temporal correlation. A new form of spatial-temporal correlation and the corresponding likelihood function are proposed, and multiple candidate model classes for the measurement error are constructed, including no correlation, spatial correlation, temporal correlation, and the proposed spatial-temporal correlation. Bayesian system identification is conducted to achieve not only the posterior probability density function (PDF) for the model parameters, but also the posterior probability of each candidate model class for selecting the most suitable/plausible model class for the measurement error. Examples are presented with applications to model updating and modal frequency prediction under varying environmental conditions, ensuring the necessity of considering correlated measurement error and the capability of the proposed Bayesian system identification in the uncertainty quantification at the parameter and model levels.

Objectives: We aimed to investigate the association between red cell distribution width-to-platelet ratio (RPR), and in-hospital mortality in critically ill patients with acute myocardial infarction (AMI)., Design: A retrospective cohort study., Setting: Data were collected from the Medical Information Mart for Intensive Care database (MIMIC-IV) consisting of critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Centre in Boston., Participants: A total of 5067 patients with AMI were enrolled from the MIMIC-IV database., Primary and Secondary Outcome: In-hospital mortality., Results: A total of 4034 patients survived, while 1033 died. In a multiple regression analysis adjusted for age, weight and ethnicity, RPR also showed a positive correlation with in-hospital mortality (HR 1.91, 95% CI 1.42 to 2.56, p<0.0001). Moreover, after adjusting for additional confounding factors, obvious changes were observed (HR 1.63, 95% CI 1.03 to 2.57, p=0.0357). In model 2, the high ratio quartile remained positively associated with hospital mortality compared with the low ratio quartile (HR 1.20, 95% CI 1.01 to 1. 43), with a p-value trend of 0.0177. Subgroup analyses showed no significant effect modifications on the association between RPR and in-hospital mortality in the different AMI groups (p>0.05)., Conclusion: RPR is an independent predictor of in-hospital mortality in critically ill patients with AMI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chukrasia tabularis is an economically important tree and widely cultured in the southeast of China. Its barks, leaves, and fruits are consumed as a traditional medicine and perceived as a valuable source for bioactive limonin compounds. The extracts from root barks of C. tabularis showed significant anti-inflammatory effect. The aim of this research was to explore the material basis of C. tabularis anti-inflammatory activity, and to purify and identify anti-inflammatory active ingredients. By a bioassay-guided isolation of dichloromethane fraction obtained two novel phragmalin limonins, Chukrasitin D and E ( 1 and 2 ), together with 12 known limonins ( 3 - 14 ). The chemical structure of these compounds is determined on the basis of extensive spectral analysis and chemical reactivity. In addition, the activities of these isolated limonins on the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa B (NF- κ B) in RAW264.7 cells induced by lipopolysaccharide (LPS) were evaluated. Limonins 1 and 2 indicated significant anti-inflammatory activity with IC 50 values of 6.24 and 6.13  μ M. Compound 1 notably inhibited the production of NF- κ B, TNF- α and interleukin 6 (IL-6) in macrophages . The present results suggest that the root barks of C. tabularis exhibited anti-inflammatory effect and the limonins may be responsible for this activity., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Objective: To construct the geometric model of the pelvic floor by a two-dimensional equivalent mechanics method, and to explore the effect of the shape and position of pelvic floor organs and tissues on the biomechanical properties of the pelvic floor under different abdominal pressure. Methods: A 28-year-old healthy and symmetrical married infertile female volunteer was included. The pelvic floor tissue was scanned in the supine position using a 3.0T magnetic resonance scanner (Philips Company, Holland). Based on the method of magnetic resonance imaging (MRI) two-dimensional parameter measurement and computer aided design, the geometric model and finite element model of the female pelvic floor were established, and the biomechanical characteristics of the pelvic floor support system under different abdominal pressure were analyzed. Results: In this study, four different working conditions of the pelvic floor force were simulated under 60, 99, 168, and 208 cmH 2 O (1 cmH 2 O=0.098 kPa) abdominal pressure loads. The trend was as follows: under the abdominal pressure load, the retrograde flexion of the uterus occurred, the cervical, the middle and upper vaginal segment and the levator anus muscle had the characteristic change of mechanical axial direction pointing to the sacrum and coccyx, and the deformation of the levator anus muscle in the horizontal direction was greater than that in the vertical direction. With the increase of the abdominal pressure, the maximum stress values of the pelvic floor whole system of healthy subjects under four different working conditions were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, respectively, and the maximum displacement values were 10, 14, 21 and 25 mm, respectively. The maximum stress values of the cervical and vaginal middle and upper segment were 0.111 7, 0.161 8, 0.250 6, and 0.304 1 MPa, respectively, and the maximum displacement values were 3, 6, 9, and 11 mm, respectively. The maximum stress of the perineal body was 0.063 4, 0.119 6, 0.235 2, and 0.288 0 MPa, and the maximum displacement was 1, 2, 4, and 5 mm. The maximum stress values of the levator anus muscle were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, and the maximum displacement values were 2, 4, 7, and 8 mm, respectively. The maximum stress and maximum displacement of pelvic organs increased with the increase of the abdominal pressure under different working conditions. The stress axial relationship of normal female pelvic floor was that the middle and upper segment of uterus and vagina mainly acted on the sacrococcyx and the levator anus muscle, and the lower vaginal segment acts on the perineal body. Conclusions: The two-dimensional equivalent mechanical modeling and finite element analysis of the female pelvic floor system can accurately reflect the biomechanical characteristics of the female pelvic floor, and the resultant stress direction of the pelvic organs points to the sacrum and coccyx. The sacrum and coccyx, levator anus and perineal body play important stress supporting roles in the pelvic floor system.

Photodetectors based on reduced graphene oxide (rGO) have attracted much attention owing to their simple and low-cost fabrication process. However, the aggregation and defects of rGO flakes still limit the performance of rGO photodetectors. Controlling the composition of rGO has become a vital factor for its prospective applications. For example, the interconnection between rGO and polymers for modified morphologies of rGO films leads to an enhanced performance of devices. In this work, a practical approach to engineer surface uniformity and enhance the performance of a photodetector by modifying the rGO film with hydrophilic polymers poly(vinyl alcohol) (PVA) is reported. Compared with the rGO photodetector, the on/off ratio for the PVA/rGO photodetector shows 3.5 times improvement, and the detectivity shows 53% enhancement even when the photodetector is operated at a low bias of 0.3 V. This study provides an effective route to realize PVA/rGO photodetectors with a low-power operation which shows promising opportunities for the future development of green systems., (© 2022 Wiley-VCH GmbH.)

In this study, 50 surface water and sediment samples were collected from 25 sampling points in Qingpu District (including Taipu River basin, Jinze Reservoir, and Qingxi country park) in the Yangtze River Delta integration demonstration area, and 22 pharmaceuticals and personal care products (PPCPs) in the samples were analyzed using high-performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS). The distribution characteristics, sources, and influencing factors of targeted PPCPs in the study area were studied in detail. The ecological and health risks of the target PPCPs were evaluated using the quotients method. The results showed that a total of 19 PPCPs were detected in the surface water and sediment samples from 25 sampling points in Qingpu District, with total concentrations ranging from 0.06 to 178.67 ng·L -1 and 0.07 to 37.68 ng·g -1 , respectively. The average value of sulfachloropyridazine (SCP) in the surface water was the highest with a concentration of 129.54 ng·L -1 , whereas the average value of sulfamethoxazole (SMX) in the sediment was the highest with a concentration of 70.62 ng·g -1 . The spatial distribution of the total amount of PPCPs showed a trend of Qingxi country park > Jinze Reservoir > Taipu River basin. Principal component analysis showed that the main sources of pollution were animal antibiotics used in aquaculture and the discharge of domestic sewage. There was a significant correlation between lg K oc and lg K d ( P <0.05), indicating that the organic carbon plays an important role in the distribution of the target PPCPs in water and sediments. The ecological risk assessment results revealed that the fungicides (TCC and TCS) in the surface waters showed a moderate risk to aquatic organisms of different trophic levels. The Qingxi country park and Jinze Reservoir were the regions with the highest ecological risks of PPCPs in surface water and sediment. The health risk entropy (HQ) of people of all age groups exposed through drinking was less than 1; however, with the continuous emission and accumulation of PPCPs, the pollution control of PPCPs in the environment still requires further attention.

The taste buds and associated glands, known as von Ebner's glands (VEGs), are involved in and augment gustatory function. The obese diabetic db/db mouse, which has defects in the leptin receptor, displays enhanced neural responses to, and an elevated behavioral preference for, sweet stimuli. However, the effect of diabetes on the morphology of circumvallate papilla (CVP) taste buds and the role of VEGs have not been investigated. The present study aimed to compare the CVP taste buds and VEGs in wildtype (Wt) and type 2 diabetic (db/db) mice. These mice were divided into control and isoproterenol-treated (at 1 h, 2 h, and 4 h after one day of fasting) groups, and were sacrificed for morphometric, immunohistochemical, and ultrastructural analyses. Morphometry revealed no significant difference in papilla size and the number of taste buds in the control and diabetic groups. Detection of PGP 9.5-immunoreactivity revealed nerve fibers in the trench wall of vallate papillae, but no significant differences were detected between groups. α-Amylase immunoreactivity levels in Wt and db/db mice were also similar. However, 1 h after isoproterenol injection, the majority of the VEG secretion of db/db mice was discharged, while the level of α-amylase was restored by 2 h after injection. The effect on α-amylase was in line with the quantitative ultrastructural analysis of the secretory granules. Our findings suggest diabetic metabolic disturbances in db/db mice do not alter the structure or innervation of CVP taste buds. However, the VEG secretory pattern was altered in db/db mice and might disrupt taste sensation.

In this study, we aim to identify the clinical significance of basonuclin 1 ( BNC1 ) expression in ovarian carcinoma (OV) and to explore its latent mechanisms. Via integrating in-house tissue microarrays, gene chips, and RNA-sequencing data, we explored the expression and clinical value of BNC1 in OV. Immunohistochemical staining was utilized to confirm the protein expression status of BNC1. A combined SMD of -2.339 (95% CI : -3.649 to -1.028, P  <   0.001) identified that BNC1 was downregulated based on 1346 samples, and the sROC (AUC = 0.93) showed a favorable discriminatory ability of BNC1 in OV patients. We used univariate and multivariate Cox regulation to evaluate the prognostic role of BNC1 for OV patients, and a combined hazard ratio of 0.717 (95% CI : 0.445-0.989, P  <   0.001) revealed that BNC1 was a protective factor for OV. Furthermore, the fraction of infiltrating naive B cells, memory B cells, and other immune cells showed statistical differences between the high- and low- BNC1 expression groups through cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Enrichment analysis showed that BNC1 may have a relationship with immune-related items in OV. By predicting the potential regulatory transcription factors (TFs) of BNC1 , friend leukemia virus integration 1 ( FLI1 ) may be a potential upstream TF of BNC1 . Corporately, a decreasing trend of BNC1 may serve as a tumor suppressor and prognostic biomarker in OV patients. Moreover, BNC1 may take part in immune-related pathways and influence the fraction of tumor-infiltrating immune cells.

Hepatocellular carcinoma (HCC) is a leading cause of mortality in cancer patients, but the association between miR-125b-2-3p and the onset and prognosis of HCC has not been reported in previous studies; thus, the clinicopathological implications of miR-125b-2-3p in HCC require elaboration. To examine the expression of miR-125b-2-3p in HCC, both in-house RT-qPCR and public datasets were used to calculate the standard mean difference (SMD) and the summary receiver operating characteristic (sROC). MiR-125b-2-3p was markedly lower in HCC than in non-tumor tissue as assessed by the in-house RT-qPCR which was confirmed by the integrative analysis showing the SMD being -0.69 and the area under the curve (AUC) being 0.84 based on 1,233 cases of HCC and 630 cases of non-HCC controls. To gain a overview of the clinical value of miR-125b-2-3p in HCC, all possible datasets were integrated, and lower miR-125b-2-3p levels could lead to poorer differentiation and a more advanced clinical stage of HCC. The hazard ratio (HR) of miR-125b-2-3p was also calculated using a Cox proportional hazards model, and the miR-125b-2-3p level could act as an protective indication for the survival with the HR being 0.74 based on 586 cases of HCC. Furthermore, the effect of nitidine chloride (NC), a natural bioactive phytochemical alkaloid, on the regulation of miR-125b-2-3p and its potential targets was also investigated. The miR-125b-2-3p level was increased after NC treatment, while the expression of its potential target PRKCA was reduced. Above all, a low-expressed level of miR-125b-2-3p plays a tumor suppressive role in HCC.

Clematis florida is widely used in She Ethnopharmacy in China owing to its significant anti-inflammatory activities. This study aimed to investigate the anti-inflammatory effect of the active fraction of C. florida (CFAF) in an arthritis animal model and its possible mechanism. Pre-inflammatory cytokine levels were examined by ELISA. CFAF can significantly improve the symptoms of arthritis such as paw swelling, arthritic index, and histological condition in AA rat. CFAF can also reduce levels of IL-1β, TNF-α and IL-6. Further studies showed that triterpene saponins from CFAF induced anti-inflammatory activity inhibited inflammatory mediators by blocking JAK/STAT signalling pathways in the LPS-treated macrophages.

Suppression of excessive hepatic gluconeogenesis is an effective strategy for controlling hyperglycemia in type 2 diabetes (T2D). In the present study, we screened our compounds library to discover the active molecules inhibiting gluconeogenesis in primary mouse hepatocytes. We found that SL010110 (5-((4-allyl-2-methoxyphenoxy) methyl) furan-2-carboxylic acid) potently inhibited gluconeogenesis with 3 μM and 10 μM leading to a reduction of 45.5% and 67.5%, respectively. Moreover, SL010110 caused suppression of gluconeogenesis resulted from downregulating the protein level of phosphoenolpyruvate carboxykinase 1 (PEPCK1), but not from affecting the gene expressions of PEPCK, glucose-6-phosphatase, and fructose-1,6-bisphosphatase. Furthermore, SL010110 increased PEPCK1 acetylation, and promoted PEPCK1 ubiquitination and degradation. SL010110 activated p300 acetyltransferase activity in primary mouse hepatocytes. The enhanced PEPCK1 acetylation and suppressed gluconeogenesis caused by SL010110 were blocked by C646, a histone acetyltransferase p300 inhibitor, suggested that SL010110 inhibited gluconeogenesis by activating p300. SL010110 decreased NAD + /NADH ratio, inhibited SIRT2 activity, and further promoted p300 acetyltransferase activation and PEPCK1 acetylation. These effects were blocked by NMN, an NAD + precursor, suggested that SL010110 inhibited gluconeogenesis by inhibiting SIRT2, activating p300, and subsequently promoting PEPCK1 acetylation. In type 2 diabetic ob/ob mice, single oral dose of SL010110 (100 mg/kg) suppressed gluconeogenesis accompanied by the suppressed hepatic SIRT2 activity, increased p300 activity, enhanced PEPCK1 acetylation and degradation. Chronic oral administration of SL010110 (15 or 50 mg/kg) significantly reduced the blood glucose levels in ob/ob and db/db mice. This study reveals that SL010110 is a lead compound with a distinct mechanism of suppressing gluconeogenesis via SIRT2-p300-mediated PEPCK1 degradation and potent anti-hyperglycemic activity for the treatment of T2D., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Pathological myocardial hypertrophy is regulated by multiple pathways. However, its underlying pathogenesis has not been fully explored. The goal of this work was to elucidate the function of polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4) in myocardial hypertrophy and its underlying mechanism of action. We illustrated that GALNT4 was upregulated in the models of hypertrophy. Two cardiac hypertrophy models were established through partial transection of the aorta in GALNT4-knockout (GALNT4-KO) mice and adeno-associated virus 9-GALNT4 (AAV9-GALNT4) mice. The GALNT4-KO mice demonstrated accelerated cardiac hypertrophy, dysfunction, and fibrosis, whereas the opposite phenotype was observed in AAV9-GALNT4 mice. Similarly, GALNT4 overexpression mitigated the degree of phenylephrine-induced cardiomyocyte hypertrophy in vitro whereas GALNT4 knockdown aggravated the hypertrophy. In terms of mechanism, GALNT4 deficiency increased the phosphorylation and activation of ASK1 and its downstream targets (JNK and p38), whereas GALNT4 overexpression inhibited activation of the ASK1 pathway. Furthermore, we demonstrated that GALNT4 can directly bind to ASK1 inhibiting its N-terminally mediated dimerization and the subsequent phosphorylation of ASK1. Finally, an ASK1 inhibitor (iASK1) was able to reverse the effects of GALNT4 in vitro. In summary, GALNT4 may serve as a new regulatory factor and therapeutic target by blocking the activation of the ASK1 signaling cascade., (© 2021. The Author(s).)

Continuum robots (CR) have been recently shown capable of micron-scale motion resolutions. Such motions are achieved through equilibrium modulation using indirect actuation for altering either internal preload forces or changing the cross-sectional stiffness along the length of a continuum robot. Previously reported, but unexplained, turning point behavior is modeled using two approaches. An energy minimization approach is first used to explain the source of this behavior. Subsequently, a kinematic model using internal constraints in multi-backbone CRs is used to replicate this turning point behavior. An approach for modeling the micro-motion differential kinematics is presented using experimental data based on the solution of a system of linear matrix equations. This approach provides a closed-form approximation of the empirical micro-motion kinematics and could be easily used for real-time control. A motivating application of image-based biopsy using 3D optical coherence tomography (OCT) is envisioned and demonstrated in this paper. A system integration for generating OCT volumes by sweeping a custom B-mode OCT probe is presented. Results showing high accuracy in obtaining 3D OCT measurements are shown using a commercial OCT probe. Qualitative results using a miniature probe integrated within the robot are also shown. Finally, closed-loop visual servoing using OCT data is demonstrated for guiding a needle into an agar channel. Results of this paper present what we believe is the first embodiment of a continuum robot capable of micro and macro motion control for 3D OCT imaging. This approach can support the development of new technologies for CRs capable of surgical intervention and micro-motion for ultra-precision tasks.

Objective: To study the clinicopathological characteristics and prognosis of eosinophilic solid and cystic renal cell carcinoma (ESC RCC). Methods: The clinical pathologic data of 4 cases of ESC RCC diagnosed and treated from 2017 to 2019 at the Second Hospital of Longyan City, the Second Affiliated Hospital of Fujian Medical University, and the Zhangzhou Municipal Hospital were collected. The expression of different antibodies was detected by immunohistochemistry, and the diagnosis and differentiate diagnosis were investigated. Results: The 4 ESC RCC cases included 2 males and 2 females, the average age of these patients was 40 years, ranged from 31 to 51 years. The tumors were composed of solid area mixed with giant vesicles and microcapsules of varying sizes. The cyst cavity was lined by neoplastic cells with voluminous eosinophilic cytoplasm and hobnail arrangement. The solid area appeared as diffuse flaky, dense acinar or nested arrangement, the local area was island-shaped and tubular, mixed with a small amount of histiocytes and lymphocytes. Neoplastic cells contained voluminous eosinophilic cytoplasm with obvious fine or coarse particles, eosinophilic globules in part of the cytoplasm, and intracytoplasmic vacuoles in some areas. Immunohistochemical results showed that tumor cells were CK20 expressed (3/3, 2 cases were sparsely positive and 1 case was patched strongly positive), Vimentin (4/4) and CD10 (4/4) sparsely positive, while Actin, HMB45, Melan-A, CD117 and CK7 were negative in all cases. Ki-67 proliferation index was about 1%. Two cases were followed up and the progression free survival were 18 and 24 months, respectively. Conclusions: ESC RCC has unique histomorphological manifestations, CK20(+ ) and CK7(-) are helpful for its diagnosis, and it has common molecular karyotype changes, supporting it as a unique tumor entity. The overall prognosis of the patient is good.

Background: The effects of circadian rhythms on drug metabolism and efficacy are being increasingly recognized. However, the extent to which they affect general anesthesia remains unclear. This study aims to investigate the effects of circadian rhythms on anesthetic depth and the concentrations of propofol target-controlled infusion (TCI)., Methods: Sixty patients undergoing laparoscopic surgeries were sequentially assigned to four groups. Group ND (n = 15): Propofol TCI with Narcotrend monitor during the day (8:00-18:00), Group NN (n = 15): Propofol TCI with Narcotrend monitor during the night (22:00-5:00), Group CLTD (n = 15): Propofol closed-loop TCI guided by bispectral index (BIS) during the day (8:00-18:00), Group CLTN (n = 15): Propofol closed-loop TCI guided by BIS during the night (22:00-5:00). The Narcotrend index, mean arterial pressure (MAP) and heart rate (HR) were compared between group ND and NN at 7 time points, from 5 min before induction to the end of operation. The propofol TCI concentrations, MAP and HR were compared between group CLTD and CLTN at 7 time points, from 5 min after induction to the end of operation., Results: The Narcotrend index, MAP, and HR in group NN were lower than those in group ND from the beginning of mechanical ventilation to the end of operation (p < 0.05). The propofol TCI concentrations in group CLTN were lower than those in group CLTD from the beginning of operation to the end of operation (p < 0.05)., Conclusion: Circadian rhythms have a significant effect on the depth of anesthesia and drug infusion concentrations during propofol TCI. When using general anesthesia during night surgery, the propofol infusion concentration should be appropriately reduced compared to surgery during the day., Trial Registration: The present study was registered on the ClinicalTrials.gov website ( NCT02440269 ) and approved by the Medical Ethics Committee of Southwest Hospital of Third Military Medical University (ethics lot number: 2016 Research No. 93). All patients provided informed written consent to participate in the study., (© 2021. The Author(s).)

To ensure safety and prevent failure of engineering equipment throughout its lifespan, the concept of 'Safety Design' is proposed, which covers all the cradle-to-grave phases of engineering equipment, considers at least ten essential factors of failure causes, and conducts root cause analysis at three different scales, in order to proactively control the safety risks before the occurrence of failure rather than passively conduct the remedial measures after failure. Herein, in order to demonstrate how to implement this effective and efficient concept in engineering practice, a case study of failure analysis and prevention is addressed on the extraction column in the production line for methyl methacrylate. Based on the analysis results, the causes were finally determined to be all derived from the stages before operation, including inappropriate design, limited quality inspection of fabrication and installation. Pertinent countermeasures were then proposed from the 'Safety Design' point of view, which would not only solve the failure problem for this sole equipment but also contribute to safety risk control of other engineering equipment before operation.

S100 calcium binding protein A9 (S100A9) is involved in a variety of biological processes such as inflammation and tumor cell migration and invasion regulation. The purpose of this study was to construct S100A9 gene-edited mice by using CRISPR/Cas9 technology, thereby providing an animal model for exploring the biological functions of this gene. According to the S100A9 gene sequence, the single-stranded small guide RNA (sgRNA) targeting exons 2 and 3 was transcribed in vitro, and a mixture of Cas9 mRNA and candidate sgRNA was injected into mouse fertilized eggs by microinjection. Early embryos were obtained and transferred to surrogate mice, and F 0 mice were obtained and identified by PCR identification and gene sequencing. F 0 mice were further mated with wild-type C57BL/6 mice to obtain F 1 heterozygous mice, and then homozygous offspring were obtained through F 1 mice self-crossing. Real-time PCR, Western blot and immunohistochemistry (IHC) were used to verify the expression and distribution of S100A9. In order to observe the pathological changes of mouse lung tissue using HE staining, an allergic asthma model was induced by ovalbumin from chicken egg white (OVA). The results showed that the 2 492 bp of exons 2, 3 of the S100A9 gene was successfully knocked out, and S100A9 -/- mice with stable inheritance were obtained. Furthermore, it was found that S100A9 gene was highly expressed in the lung and spleen of wild-type mice. The expression of S100A9 mRNA and protein was not detected in the lung and spleen of S100A9 -/- mice. However, compared with wild-type mice, the lungs of S100A9 -/- mice showed a significantly worse inflammatory phenotype, and the proportion of eosinophils in bronchoalveolar lavage fluid (BALF) was significantly increased in response to the treatment of OVA. These results suggest we have successfully constructed a new strain of S100A9 -/- mice, and preliminarily confirmed that the lack of S100A9 function can aggravate airway inflammation in asthmatic mice, providing a new mouse model for further study of S100A9 gene function.

In order to reveal the impact of the application of biogas slurry instead of chemical nitrogen fertilizer on the environmental risk of heavy metals in the soil by returning straw to the field, four treatments, without biogas slurry and without straw applications (CK), biogas slurry application without straw (B), straw application without biogas slurry (S), and biogas slurry combined with straw applications (BS), were applied in a typical coastal reclaimed farmland (rice-wheat rotation) in Jiangsu province. The migration and morphological characteristics of Cu, Zn, Cd, and Pb in different soil layers were observed, and the potential environmental risks were estimated. The results showed that:① The total amounts of Zn and Pb in the surface soils (0-20 cm) in the rice and wheat fields under the BS treatment decreased significantly ( P <0.05). The four heavy metals in the paddy soils migrated 6%-11% from the surface to the middle and lower layers (20-60 cm), and Cu, Cd, and Pb in the wheat soils migrate down from the surface by 25% to 33%. This indicated that the combined use of biogas slurry and straw accelerates the vertical downward movement of heavy metals in the surface soil. ② Under the BS treatment, the contents of the weak acid extraction of Cu in the surface soil of the paddy field decreased by 8.8%, and the residual state of Zn, Cd, and Pb decreased by 7.0% to 14.2%. This revealed that Cu was passivated, but Zn, Cd, and Pb tended to be activated. In comparison, the reduction in Cu residues in wheat field surface soil was 2.8 times that of the weak acid extraction, indicating that Cu was activated. Furthermore, the residue state of Cd increased, the weak acid extraction state of Pb decreased, and Cd and Pb were passivated. ③ The ecological risk assessment of heavy metals showed that there is no ecological risk in the soils under the BS treatment, and the risk indices were significantly lower than those of the B and S treatments ( P <0.05). Therefore, the combined use of biogas slurry and straw helps to significantly reduce the risk of heavy metal pollution in the soils in the coastal reclamation areas.

Organic pollutants in electroplating wastewater can be removed by photodegradation, however the effect mechanism of heavy metal ions on photocatalytic activity still remains unknown. Herein, we firstly reported the self-assembly synthesis of titanium dioxide/reduced graphene oxide (TiO 2 /rGO) composites for phenol-4-sulfonic acid (PSA) removal, and investigated the effects of Cu 2+ ions on photocatalytic efficiency. During the self-assemble process, rGO nanosheets were connected together to form network macropores, and simultaneously induced the deposition of hierarchically nanostructured TiO 2 microspheres. The synergetic effects of TiO 2 microspheres and rGO nanosheets improved the photocatalytic activity by enhancing light adsorption ability, stabilizing electron-hole separation and decreasing band gap energy. The Cu 2+ ions in wastewater showed positive and negative effects on PSA photodegradation. In the photocatalytic reaction, the electron-induced reduction reaction of Cu(II) into Cu(0) or Cu(I) took place, which inhibited electron-hole recombination and thus enhanced photocatalytic activity. However, the high chemical stability of PSA-Cu(II) complex compounds held back PSA photodegradation. The appropriate concentrations of Cu 2+ ions at around 25 mg/L accelerated PSA photodegradation over TiO 2 /rGO composites. The PSA degradation into CO 2 and H 2 O was performed by using hydroquinone, benzoquinone and maleic acid as degradation intermediates. Hence, TiO 2 /rGO composites are novel multifunctional photocatalysts to purify electroplating wastewater., 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 © 2020 Elsevier Inc. All rights reserved.)

Functional electrical stimulation is an effective way to rebuild hindlimb motor function after spinal cord injury. However, no site map exists to serve as a reference for implanting stimulator electrodes. In this study, rat models of thoracic spinal nerve 9 contusion were established by a heavy-impact method and rat models of T6/8/9 spinal cord injury were established by a transection method. Intraspinal microstimulation was performed to record motion types, site coordinates, and threshold currents induced by stimulation. After transection (complete injury), the core region of hip flexion migrated from the T13 to T12 vertebral segment, and the core region of hip extension migrated from the L1 to T13 vertebral segment. Migration was affected by post-transection time, but not transection segment. Moreover, the longer the post-transection time, the longer the distance of migration. This study provides a reference for spinal electrode implantation after spinal cord injury. This study was approved by the Institutional Animal Care and Use Committee of Nantong University, China (approval No. 20190225-008) on February 26, 2019., Competing Interests: None

By exploiting variation both in mortgage payoffs and mortgage interest-rate resets, we find that a decline in mortgage payments induces a significant increase in nondurable goods spending, even when households have substantial amounts of liquidity. Following mortgage payoff, households increase consumption expenditures by 61% of the original payment. In comparison, households increase consumption by only 36% in response to a transitory payment adjustment induced by interest rate changes. Households with a higher payment-to-income ratio have a significantly lower marginal propensity to consume (MPC). These results have practical implications for policy markers seeking to design consumption boosting policies and are important for understanding how changes in monetary policy may affect consumer spending patterns., Competing Interests: This is to certify that we have no conflict of interests with other parties., (© 2020 Published by Elsevier B.V.)

Background: The potential effectiveness of integrated management in further improving the prognosis of patients with atrial fibrillation has been demonstrated; however, the best strategy for implementation remains to be discovered., Objective: The aim of this study was to ascertain the feasibility of implementing integrated atrial fibrillation care via the Hospital-Community-Family-Based Telemedicine (HCFT-AF) program., Methods: In this single-arm, pre-post design pilot study, a multidisciplinary teamwork, supported by efficient infrastructures, provided patients with integrated atrial fibrillation care following the Atrial fibrillation Better Care (ABC) pathway. Eligible patients were continuously recruited and followed up for at least 4 months. The patients' drug adherence, and atrial fibrillation-relevant lifestyles and behaviors were assessed at baseline and at 4 months. The acceptability, feasibility, and usability of the HCFT-AF technology devices and engagement with the HCFT-AF program were assessed at 4 months., Results: A total of 73 patients (mean age, 68.42 years; 52% male) were enrolled in November 2019 with a median follow up of 132 days (IQR 125-138 days). The patients' drug adherence significantly improved after the 4-month intervention (P<.001). The vast majority (94%, 64/68) of indicated patients received anticoagulant therapy at 4 months, and none of them received antiplatelet therapy unless there was an additional indication. The atrial fibrillation-relevant lifestyles and behaviors ameliorated to varying degrees at the end of the study. In general, the majority of patients provided good feedback on the HCFT-AF intervention. More than three-quarters (76%, 54/71) of patients used the software or website more than once a week and accomplished clinic visits as scheduled., Conclusions: The atrial fibrillation-integrated care model described in this study is associated with improved drug adherence, standardized therapy rate, and lifestyles of patients, which highlights the possibility to better deliver integrated atrial fibrillation management., Trial Registration: Clinicaltrials.gov NCT04127799; https://clinicaltrials.gov/ct2/show/NCT04127799., (©Jiang Jiang, Xiang Gu, Chen-Di Cheng, Hong-Xiao Li, Xiao-Lin Sun, Ruo-Yu Duan, Ye Zhu, Lei Sun, Fu-Kun Chen, Zheng-Yu Bao, Yi Zhang, Jian-Hua Shen. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 21.10.2020.)