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Chung-Wei Lin,1,2,* Yung-Chun Su,3 Jin-Dien Liu,2,4 Hsiao-Chun Su,5 Ting-Yi Chiang,6 Li-Wen Chiu,7 Hsin-Ching Lin,1,8– 11,* Chun-Tuan Chang,9 Pei-Wen Lin7,8,10 1Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2Department of Education, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3Department of General Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 4Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 5School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Department of Urology, Chi Mei Medical Center, Tainan, Taiwan; 7Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 8College of Medicine, Chang Gung University, Taoyuan, Kaohsiung, Taiwan; 9Department of Business Management, Institute of Healthcare Management, National Sun Yat-Sen University, Kaohsiung, Taiwan; 10Institute of Biomedical Science, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; 11Sleep Center, Robotic Surgery Center and Center for Quality Management Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Pei-Wen Lin, Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung District, Kaohsiung City, 833, Taiwan, Tel +886-7-7317123 ext.2801, Fax +886-7-7777152, Email lpw324@cgmh.org.tw, lpw324@gmail.comAbstract: Obstructive sleep apnea (OSA) has been reported to influence the ocular surface and may lead to dry eye disease (DED). Continuous positive airway pressure (CPAP) is the first-line conservative treatment for OSA. However, CPAP might also have mask-related side effects that could deteriorate DED simultaneously. This study investigated the impact of OSA on DED (Aim 1), and CPAP on DED (Aim 2). Five databases were searched for articles published up to May, 2024. OSA severity, CPAP usage, and DED parameters, including tear breakup time (TBUT), Schirmer test, Ocular Surface Disease Index (OSDI), and Corneal Fluorescence Staining Score (CFS), were analyzed. For Aim 1, the random-effects model was used for meta-analysis, and the leave-one-out method was used for sensitivity analysis. For Aim 2, a narrative synthesis with critical appraisal of the literature was performed. Eleven studies with 1,526 patients for Aim 1 and three studies with 180 patients for Aim 2 were included. For Aim 1, OSA patients had poorer dry eye profiles of TBUT, Schirmer test, and OSDI when compared to non-OSA patients. For Aim 2, it seemed that those wearing CPAP for less than half a year did not have enough improvement in dry eye status. Instead, those wearing CPAP for at least a year reached greater therapeutic effects for OSA and DED. We concluded that OSA patients may suffer from poorer dry eye condition compared to non-OSA patients. Besides, wearing CPAP for long enough duration (at least 1 year) seemed to have better improvement in DED.Keywords: Obstructive sleep apnea, continuous positive airway pressure, dry eye disease, meta-analysis

Jian-Feng Li,1 Guang-Lei Tian,2 Hui Pan,3 Wen-Tong Zhang,1 Da-Cun Li,1 Jing-Da Liu,1 Liang Zhao,1 Hai-Lei Li1 1Department of Hand Surgery, Beijing Shunyi District Hospital; Shunyi Teaching Hospital of Capital Medical University, Beijing, 101300, People’s Republic of China; 2Department of Hand Surgery, Beijing Jishuitan Hospital; Peking University Fourth School of Clinical Medicine, Beijing, 100035, People’s Republic of China; 3Department of Pathology, Beijing Shunyi District Hospital; Shunyi Teaching Hospital of Capital Medical University, Beijing, 101300, People’s Republic of ChinaCorrespondence: Jian-Feng LiDepartment of Hand Surgery, Beijing Shunyi District Hospital; Shunyi Teaching Hospital of Capital Medical University, No. 3 Guangming South Street, Shunyi District, Beijing, 101300, People’s Republic of China, Tel +86 10 69423220, Email drlijf27@126.comObjective: This study aimed to explore the pathogenic genes and mutation sites of macrodactyly.Methods: Whole-exome sequencing was performed on the pathological tissue and peripheral blood of 12 patients with macrodactyly who were operated in our hospital between June 2018 and May 2020. In order to conduct comprehensive bioinformatics analysis and screen the pathogenic genes of macrodactyly, the patients were divided into four groups: macrodactyly of finger group, macrodactyly of foot group, macrodactyly and syndactyly of finger group, and macrodactyly and syndactyly of foot group. The results of the whole-exome sequencing were verified using Sanger sequencing in order to clarify the pathogenic genes and mutation sites of macrodactyly, and immunohistochemical analysis of the protein signaling pathways encoded by the pathogenic genes was performed to observe the protein expression and further verify the mutant genes.Results: In the comprehensive bioinformatics analysis and Sanger verification of the whole-exome sequencing, the PIK3CA gene mutation was screened as the pathogenic gene of macrodactyly. The mutation sites were identified as the p.E542K (c.G1624A) and p.E545K (c.G1633A) sites of exon10 and the p.H1047R (c.A3140G) and p.G1049R (c.G3145C) sites of exon21. Among these, the p.G1049R (c.G3145C) locus was found in macrodactyly for the first time. The mutation of the PIK3CA gene was also found to lead to increased expression of serine-threonine kinase (AKT) in adipocytes in the PI3K-AKT-mTOR signaling pathway.Conclusion: Mutation of the PIK3CA gene leads to the enhancement of the PI3K-AKT-mTOR signaling pathway, which is the cause of macrodactyly. There is also some diversity in PIK3CA gene mutation sites.Keywords: hand deformity, foot deformity, macrodactyly, PIK3CA gene

Lafora disease (LD) is a severe autosomal recessive disease, which usually presents as seizure and myoclonus, followed by behavioral changes, dysarthria, intellectual decline, and finally progressed to dementia and a vegetative state. The main cause of LD is the loss-of-function mutations in EPM2A and NHLRC1 that encode laforin and malin, respectively. Targeted genetic testing is the gold standard to confirm the diagnosis of LD. To describe the pathogenic role of biallelic EPM2A intronic mutations carried by patients in a family diagnosed as LD. Here, we present clinical findings in a patient presenting with epileptic seizures and Lafora bodies in muscle biopsy. Long-read DNA and RNA sequencing were performed to identify the causative mutation. Western blot and qPCR confirmed the pathogenic role of biallelic EPM2A intronic mutations. Genetic testing identified two intronic mutations in EPM2A which caused aberrant mRNA splicing. c.301+1 G > A in EPM2A caused aberrant splicing at donor site and resulted in intron retention in transcript NM_005670.4, while c.476+14860 C > A caused aberrant splicing in transcript NM_001368129.2 and NM_001368132.1. Our findings expand the spectrum of variants in LD disease, additionally providing evidence linking non-coding regulatory regions mutations to LD disease., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

As an important potential dust suppression method, the slow onset time is one of the key factors that restrict the effect of microbial dust suppressant. In the early stage, we have confirmed that extracellular polymeric substances (EPS) can improve the dust suppression effect by wetting coal dust and increasing Ca 2+ nucleation sites. Therefore, in this study, chitosan (CTS) and bovine serum albumin (BSA) in different ratios (CTS: BSA = 1:1, 1:2, 2:1) as model molecules of EPS were combined with Bacillus subtilis to prepare efficient and fast microbial dust suppressants. Furthermore, the interaction forces were analyzed through molecular dynamics simulation. Results showed that adding CTS and BSA would improve the dust suppression effect, and the dust suppression effect was the best when the ratio of CTS: BSA was 1:2. In addition, the contact angle decreased as the BSA content increased. The Fourier transform infrared spectroscopy (FTIR) results showed that when the ratio of CTS to BSA was 1:2, the dust suppressants were easier to interact with coal dust by the key functional groups and form calcite type CaCO 3 . The molecular dynamics simulation results showed that the main interaction was Van der Waals force. In addition, the interaction force was strongest when CTS: BSA was 1:2, increasing by 137% compared with the microbial dust suppressants without CTS or BSA. This study provides theoretical support for the development of efficient and rapid microbial dust suppressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bacterial biofilms are a significant concern in various medical contexts due to their resilience to our immune system as well as antibiotic therapy. Biofilms often require surgical removal and frequently lead to recurrent or chronic infections. Therefore, there is an urgent need for improved strategies to treat biofilm infections. Ultrasound-mediated drug delivery is a technique that combines ultrasound application, often with the administration of acoustically-active agents, to enhance drug delivery to specific target tissues or cells within the body. This method involves using ultrasound waves to assist in the transportation or activation of medications, improving their penetration, distribution, and efficacy at the desired site. The advantages of ultrasound-mediated drug delivery include targeted and localized delivery, reduced systemic side effects, and improved efficacy of the drug at lower doses. This review scrutinizes recent advances in the application of ultrasound-mediated drug delivery for treating biofilm infections, focusing on in vivo studies. We examine the strengths and limitations of this technology in the context of wound infections, device-associated infections, lung infections and abscesses, and discuss current gaps in knowledge and clinical translation considerations., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Growing demand for wound care resulting from the increasing chronic diseases and trauma brings intense pressure to global medical health service system. Artificial skin provides mechanical and microenvironmental support for wound, which is crucial in wound healing and tissue regeneration. However, challenges still remain in the clinical application of artificial skin since the lack of the synergy effect of necessary performance. In this study, a multi-functional artificial skin is fabricated through microfluidic spinning technology by using core-shell gel nanofiber scaffolds (NFSs). This strategy can precisely manipulate the microstructure of artificial skin under microscale. The as-prepared artificial skin demonstrates superior characteristics including surface wettability, breathability, high mechanical strength, strain sensitivity, biocompatibility and biodegradability. Notably, this artificial skin has the capability to deliver medications in a controlled and sustained manner, thereby accelerating the wound healing process. This innovative approach paves the way for the development of a new generation of artificial skin and introduces a novel concept for the structural design of the unique core-shell gel NFSs., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The association between the number of food kinds and the risk of depression in adults was examined., Methods: According to the inclusion and exclusion criteria, a total of 4593 adults were included in the study. The number of food kinds was collected via 24‒hour dietary recalls. Depression was assessed using the Patient Health Questionnaire‒9. Logistic regression and restricted cubic spline models were applied to assess the association between the number of food kinds and the risk of depression., Results: This study included 4593 study participants, 451 of whom were diagnosed with depression. The revised advantage ratios (with corresponding confidence intervals) for the prevalence of depression among individuals in the fourth quartiles of the number of food kinds (Q4) in comparison to the lowest quartile (Q1) were determined to be 0.59 (0.36‒0.96), respectively. According to our subgroup analyses, the number of food kinds was negatively associated with the risk of depression in females, participants aged 18‒45 and 45‒65 years, and participants with a body mass index (BMI) of 25 to 24.9 kg/m 2 . According to our dose‒response analysis, the number of food kinds was linearly associated with the risk of depression (P for nonlinear =0.5896)., Conclusion: The risk of depression exhibited a linear and negative correlation with the number of food kinds. The results indicated that a diversified diet was an effective nonpharmacological approach that deserved further generalization., (© 2024. The Author(s).)

Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases., (© 2024. The Author(s).)

Purpose: The present study aimed to further examine the factor structure and measurement invariance of the UDRQ among a sample of Hungarian university students., Methods: Firstly, the factor structure of the UDRQ was examined among 837 Hungarian university students. Specifically, two measurement models (first-order model and second-order model) were constructed and compared. Secondly, the internal consistency reliability of the UDRQ was examined. Thirdly, measurement invariance of the UDRQ was evaluated across genders. Finally, measurement invariance of the UDRQ was evaluated across two different samples., Results: It was found that the first-order model outperformed the second-order model and better represented the factor structure of the UDRQ subscales. Results of Cronbach's alpha and Composite Reliability suggested that the internal consistency reliabilities of the two UDRQ subscales were satisfactory. Measurement invariance analysis revealed that the UDRQ measurement model was strict invariant across genders and samples., Conclusion: The findings of the present study indicated that the UDRQ displayed satisfactory reliability and validity and could be used to assess demands and resources of Hungarian university students., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sun, Chen, Sun, Szabó, Tóth, Hu, Jagodics and Liu.)

The theory of heat conduction paths has been widely recognized and widely studied in the research about the thermal conductivity of thermal conductive polymer composites at present. Encapsulating polymer pellets with thermally conductive fillers and processing them into thermally conductive polymer composites is a simple and effective method for constructing heat conduction paths. It is meaningful to investigate the related heat conduction mechanism of this method. Otherwise, this approach can significantly preserve the performance of the polymer substrate, making it highly valuable for practical material applications. In this work, polyethylene-octene elastomer (POE) pellets were encapsulated with thermal conductive fillers by physical absorption. Subsequently, the composite films containing heat conduction paths were fabricated using the encapsulated POE pellets through a heating press. Alumina (Al 2 O 3 ), boron nitride (BN), and alumina/boron nitride hybrid (Al 2 O 3 /BN) fillers were used to prepare Al 2 O 3 @POE, BN@POE, and BN/Al 2 O 3 @POE composite films to investigate the influence of filler shapes on heat conduction path construction. The influence of the constitute and density of heat conduction paths on the thermal conductivity of composite films was analyzed by infrared thermal imaging, finite element analysis, and thermal resistance theory in detail. Owing to the reserved good adhesion and flexibility of the POE substrate, the composite films could be directly used as thermal interface materials for chip cooling, which presented a good heat dissipation effect. Furthermore, a series of integrated composite materials were prepared by the combination of encapsulated pellets with various functional films (copper foil, aluminum foil, and graphite sheet) through a one-pot heating press, exhibiting a good electromagnetic shielding effect. The performance of the composites and the corresponding preparation method demonstrate the strong significance of this research for practical applications.

The current study presents the development process and initial validation of the Engagement in Athletic Training Scale (EATS), which was designed to evaluate athletes' engagement in athletic training. In study 1, item generation and initial content validity of the EATS were achieved. In study 2, the factor structure of the EATS was examined using exploratory factor analysis (EFA) and exploratory structural equation modeling (ESEM). Internal consistency reliabilities of the subscales were examined ( N  = 460). In study 3, factor structure, discriminant validity, internal consistency reliability, and nomological validity of the EATS were further examined in an independent sample ( N  = 513). Meanwhile, measurement invariance of the EATS across samples (study 2 and study 3) and genders was evaluated. Overall, results from the 3 rigorous studies provided initial psychometric evidence for the 19-item EATS and suggested that the EATS could be used as a valid and reliable measure to evaluate athletes' engagement in athletic training., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liu, Wu, Zou, Wang, Zhang, Hu and Liu.)

Objective: To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We designed, developed, and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection. The precision of the liquid transfer and temperature control was tested. A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The entire process, from SARS-CoV-2 nucleic acid extraction to amplification, was evaluated., Results: The precision of the syringe transfer volume was 19.2 ± 1.9 μL (set value was 20), 32.2 ± 1.6 (set value was 30), and 57.2 ± 3.5 (set value was 60). Temperature control in the amplification tube was measured at 60.0 ± 0.0 °C (set value was 60) and 95.1 ± 0.2 °C (set value was 95) respectively. SARS-Cov-2 nucleic acid extraction yield through the device was 7.10 × 10 6 copies/mL, while a commercial kit yielded 2.98 × 10 6 copies/mL. The mean time to complete the entire assay, from SARS-CoV-2 nucleic acid extraction to amplification detection, was 36 min and 45 s. The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL., Conclusion: The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test (POCT)., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objective: To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC). Methods: Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups. Results: The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ 2 =234.215, P <0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ 2 =34.378, P <0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ 2 =30.642, P <0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ 2 =274.474, P <0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ 2 =17.535, P =0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ 2 =6.764, P =0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ 2 =4.093, P =0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group ( P <0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ 2 =23.741, P <0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ 2 =6.247, P =0.012). Conclusion: EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

Introduction: Elite athletes' help-seeking on mental health might be influenced by their mental health literacy (MHL) and mental health experiences. The current study aimed to explore the MHL, experiences and help-seeking behaviours among elite athletes using a qualitative approach., Methods: Face-to-face semi-structured interviews were conducted among 20 Chinese elite athletes, 12 coaches, and 5 team officials. Interview data was analyzed using content analysis., Results: Seven main themes emerged from the analysis. The current study revealed that Chinese elite athletes suffered from various mental health issues and athletes' MHL levels, help-seeking attitudes and intentions, Chinese sports environments, and Chinese cultural background could impact their help-seeking behaviours., Conclusion: Support for Chinese elite athletes' mental health and help-seeking requires improvement., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bu, Zhang, Liu, Han, Wang and Huang.)

Purpose: Psychological resilience is vital to the development of sport talents. Qualitative research has consistently demonstrated that sport resilience encapsulates a mixed package of resilience qualities (reflecting positive traits and characteristics) and resilience support (reflecting perceived support and related resources). Ironically, sport resilience research adopting quantitative methods has been assessing resilience as a unidimensional construct, with little attention to the multi-facet nature of resilience and its effects on performance. In the present research, we tested a novel proposition that resilience qualities predict reduced pre-competition cognitive anxiety and contribute to performance more than resilience support. Methods & Results: Across two samples of competitive table tennis players (Study 1: N = 196 competing at province level; Study 2: N = 106 competing at national level), we consistently found resilience qualities, rather than resilience support, predicted lower levels of pre-competition cognitive anxiety and superior performance at a national championship. Results also suggest that pre-competition cognitive anxiety mediated the relationship between resilience qualities and performance. Conclusion: The findings provide the first evidence supporting the divergent effects of resilience qualities and resilience support in predicting pre- competition anxiety and championship performance and call for the consideration of such a distinction when designing and delivering resilience programs.

Objective: To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies. Methods: In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups. Results: The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2 =54.816, P <0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2 =32.355, P <0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2 =30.777, P <0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2 =69.639, P <0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2 =6.034, P =0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2 =11.644, P =0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P >0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2 =16.301, P <0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2 =5.442, P <0.001). HER-2 and Epstein-Barr virus positivity rates did not differ significantly between the two groups. Conclusion: Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Supramolecular carrier-mediated chemotherapy is a highly attractive strategy for targeted drug delivery. In this study, four novel biotin-linked calix[4]arenes BPCA1-BPCA4 have been rationally designed to construct nano-complex with doxorubicin. The in vitro and in vivo assessments reveal that BPCA4-DOX with excellent stability are capable of affording significantly superior anti-tumor activity and lower side effects.

In recent years, the situation of ozone pollution in China has become increasingly severe, with PM 2.5 being the main pollutant in the atmospheric environment of several cities. Meteorological conditions, particularly temperature and humidity, have a great influence on ozone formation. Therefore, understanding and quantifying the impact of the variation in temperature and humidity on ozone level can effectively provide the theoretical basis for the government to prevent and control ozone pollution. By analyzing the relationship among the daily maximum temperature ( T max ), relative humidity (RH), and the maximum 8-h running average ozone (O 3 -8h) measured from January 1, 2015 to July 31, 2022, a linear positive correlation between O 3 -8h and T max was observed in the seven regions with serious ozone pollution, and the temperature penalty factor ranged from 2.1-6.0 μg·(m 3 ·℃) -1 ; a nonlinear correlation between O 3 -8h and RH was also observed, and O 3 -8h was the highest when RH was 55%. The sensitivity of different regions to T max and RH was slightly different; generally, the most suitable meteorological conditions for ozone formation were 29℃ ≤ T max < 38℃ and 40% ≤ RH<70%. In the Yangtze River Delta, Jiangsu-Anhui-Shandong-Henan, and the middle reaches of the Yangtze River, under extreme high temperature conditions ( T max ≥ 35℃), O 3 -8h stopped increasing with the increase in temperature and even dropped; simultaneously, it was often accompanied with a small increase in particulate matter. It may be related to the heterogeneous reaction of some precursors with higher water vapor content and the increase in ozone heterogeneous sink.

Objectives: The present study aimed to examine the psychometric properties of the Chinese version of the Career Adapt-Abilities Scale-Short Form (CAAS-SF) among a sample of Chinese elite athletes., Methods: A sample of Chinese elite athletes ( n = 770) was invited to participate in this study. First, the factor structure of the Chinese version of the CAAS-SF was examined, and six measurement models (CFA, H-CFA, B-CFA, ESEM, H-ESEM, and B-ESEM) were constructed and compared. Second, the internal consistency reliability of the Chinese version of the CAAS-SF was examined. Finally, structural equation modeling (SEM) was employed to assess the nomological validity of the Chinese version of the CAAS-SF., Results: The results showed that the hierarchical ESEM (H-ESEM) model best represented the factor structure of the CAAS-SF among Chinese elite athletes. It suggests that the higher-order factor of career adaptability explains the four distinctive but interrelated specific factors of concern, control, curiosity, and confidence. Cronbach's alpha coefficients (0.84-0.90), composite reliability (0.81-0.96), and coefficient omega hierarchical (0.855-0.94) of the Chinese version of the CAAS-SF were larger than the cutoff values, which suggest satisfactory reliability. The results of the SEM revealed that the higher-order factor of career adaptability was positively associated with career decision self-efficacy (β = 0.676, p < 0.001). This result is consistent with previous findings (r = 0.65, p < 0.01) and provided support for the nomological validity of the CAAS-SF among Chinese elite athletes., Conclusion: The findings of the present study indicated that the Chinese version of the CAAS-SF displayed satisfactory reliability and validity and could be used to assess the career adaptability of Chinese elite athletes. In addition, the total score of the CAAS-SF is suggested to be used in future research and practical works., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Su, Huang, Zou, Liu and Liu.)

Objective: The purpose of the study was to develop and initially validate a context-specific scale assessing Career Self-Management for Chinese coaches (Career Self-Management Scale-CC; CSMS-CC)., Methods: Firstly, qualitative data obtained from in-depth interview with coaches were contently analyzed to generate potential CSMS-CC items. The content validity of the items was evaluated by a panel of experts. Secondly, the factor structure and item performance of the CSMS-CC were examined using exploratory factor analysis (EFA) and internal consistency reliability of its subscales were evaluated in sample 1 ( n = 229, 24.01% females). Thirdly, factor structure of the CSMS-CC was further examined using confirmatory factor analysis (CFA) in sample 2 ( n = 295, 32.54% females). Internal consistency reliability was evaluated using Cronbach' alpha coefficient and composite reliability. Nomological validity was examined using Pearson correlation and structural equation modeling (SEM) by investigating the correlations between CSMS-CC subscales with career success. Finally, measurement invariance and latent mean difference of the CSMS-CC was examined across gender, professional title and coaching class using multiple-group CFA (MGCFA)., Results: Based on the results of the content analysis and content validity evaluation, 18 CSMS-CC items were retained for further analysis. Results of EFA in sample 1 revealed that eight items were problematic and removed. The second round of EFA revealed that three components were retained and labelled as Networking Behavior (4 items), Training Exploration (3 items), and Guanxi Development (3 items). Results of CFA in sample 2 suggested that the 10-item three-correlated-factors model of CSMS-CC demonstrated acceptable model fit to the data, χ 2 = 135.01, df = 32, p < 0.01, CFI = 0.91, TLI = 0.90, SRMR = 0.05, RMSEA = 0.092 (90% CI = 0.076-0.108). Composite reliability (ranging from 0.84 to 0.88) and Cronbach's alpha coefficients (ranging from 0.78 to 0.81) of three subscales were found satisfactory. Nomological validity was supported by the results that total score and subscale scores of the CSMS-CC were significantly associated with internal marketability and external marketability. It was found that the CSMS-CC measurement model was strict invariant across gender, professional title and coaching class. Significant differences on all three subscales across professional title and on Guanxi development across coaching class were revealed., Conclusion: Results of this study provided initial support for the psychometric properties of the 10-item CSMS-CC, which suggested that the CSMS-CC could be used for measuring the career self-management of Chinese coaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang and Liu.)

Fumonisins (FUM) and deoxynivalenol (DON) are two common mycotoxins in poultry feed. Salmonella enterica ser. Enteritidis (S. Enteritidis) is a primary foodborne bacterium in broilers. This trial was conducted to evaluate the effects of naturally occurring FUM and DON and their combination at subclinical doses on broiler performance during a S. Enteritidis challenge. The experiment consisted of five treatments: NCC, no-challenge no-mycotoxin treatment; CC, Salmonella challenge + no-mycotoxin treatment; DON, DON 0.6 mg/kg + Salmonella challenge; FUM, FUM 14 mg/kg + Salmonella challenge; DON + FUM + T-2 + neosolaniol, DON 0.6 mg/kg + FUM 14 mg/kg + T-2 toxin 0.6 mg/kg + 0.8 mg/kg neosolaniol + Salmonella challenge. On d 4, birds were challenged with either 0 or 1 × 10 9 CFU/mL S. Enteritidis orally. There were no significant effects on growth performance among treatments at 0, 3, 7, and 14 d of post-inoculation (dpi). On 14 dpi, the combined DON + FUM + T-2 + neosolaniol significantly increased the Salmonella load by 1.5 logs compared to the control groups (P < 0.05). FUM significantly increased the cecal tonsil IL-10 gene expression by 1.2-fold at 7 dpi (P < 0.05) and downregulated TNF-α by 1.8-fold on 14 dpi compared to the control, nonchallenge groups (P < 0.05). On 7 dpi, the combined DON + FUM + T-2 + neosolaniol reduced occludin by 4.4-fold (P < 0.05) when compared to the control groups. Similarly, combined DON + FUM+ T-2 + neosolaniol decreased zona-occluden transcription by 2.3 and 7.6-fold on 3 and 14 dpi, respectively (P < 0.05). Furthermore, combined DON + FUM + T-2 + neosolaniol decreased Claudin-1 by 2.2-fold and Claudin-4 by 5.1-fold on 14 dpi when compared to the control groups (P < 0.05). In conclusion, short-term exposure to a subclinical dose of combined DON + FUM + T-2 + neosolaniol had an impact on broiler intestinal tight junction proteins and cecal Salmonella abundance under experimental Salmonella challenge., (Published by Elsevier Inc.)

Background: This study aimed to (1) explore the quality of life (QoL) profiles of older adults in Hong Kong and (2) examine their association with predictors (age, sex, body mass index, and depressive symptoms) and distal outcome (cognitive impairment) using a person-centered approach., Methods: A total number of 328 community-dwelling older adults in Hong Kong were invited to participate in this study. Data from 259 older adults were identified as valid for the primary analysis. Latent profile analysis was used to explore QoL profiles. Multinomial logistic regression using the R3STEP function in Mplus was used to explore the predictive role of age, sex, body mass index, and depressive symptoms in profile membership. The Bolck-Croon-Hagenaars approach was used to examine how the distal outcome of cognitive impairment differs as a function of QoL profiles., Results: Three QoL profiles emerged from the latent profile analysis (Low, Moderate and High QoL). It was found that depression, but not age, sex, or body mass index, significantly predicted QoL profile membership. The results of the Bolck-Croon-Hagenaars analysis revealed no significant differences in cognitive impairment across the three QoL profiles., Conclusion: This is the first study that examined the relationship between QoL, depressive symptoms and cognitive impairment of older adults using a person-centered approach. The findings provide additional information for the evidence obtained from variable-centered approach on the associations among variables abovementioned. Our additional focus on the antecedents of emergent QoL profiles also provide practical knowledge regarding timely treatment for or prevention of depressive symptoms, which we submit will be crucial for enhancing the QoL of older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luo, Li, Wu, Wei, Zang and Liu.)

This study aimed to investigate the clinical characteristics and major adverse cardiovascular events (MACEs) of Chinese patients with premature acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study was a secondary retrospective analysis involving 2114 ACS patients undergoing PCI at a single center in China. The patients were divided into two groups according to age (premature ACS group: ≤ 55 years in men, ≤ 65 years in women; nonpremature ACS group: > 55 years in men, > 65 years in women). The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel revascularization, and recurrent angina at follow-up, defined as MACEs. The incidence of all-cause death and MACEs was significantly lower in the premature than in the nonpremature ACS group (P < 0.001). Female sex, higher triglyceride levels, and higher low-density lipoprotein cholesterol levels were identified as independent risk factors that accelerated the development of ACS, whereas higher high-density lipoprotein cholesterol levels were identified as protective factors. Furthermore, in patients with premature ACS, non-ST-elevation ACS, cardiac insufficiency, multivessel disease, and left main lesion were risk factors for MACEs. Younger individuals, especially females, are advised to undergo early screening for the risk factors of premature ACS. Primary prevention of dyslipidemia should be more aggressively promoted at a young age. For premature ACS patients undergoing PCI, strengthened management and regular re-examinations are necessary to avoid adverse cardiovascular events as much as possible.

In order to solve the dust problem caused by sandstorms, this paper aims to propose a new method of enriching urease-producing microbial communities in seawater in a non-sterile environment. Besides, the difference of dust suppression performance of enriched microorganisms under different pH conditions was also explored to adapt the dust. The Fourier-transform infrared spectrometry (FTIR) and Scanning electron microscopy (SEM) confirmed the formation of CaCO 3 . The X-ray diffraction (XRD) further showed that the crystal forms of CaCO 3 were calcite and vaterite. When urease activity was equivalent, the alkaline environment was conducive to the transformation of CaCO 3 to more stable calcite. The mineralization rate at pH = 10 reached the maximum value on the 7 th day, which was 97.49 ± 1.73%. Moreover, microbial community analysis results showed that the relative abundance of microbial community structure was different under different pH enrichment. Besides, the relative abundance of Sporosarcina, a representative genus of urease-producing microbial community, increased with the increase of pH under culture conditions, which consistent with the mineralization performance results. In addition, the genus level species network diagram also showed that in the microbial community, Sporosarcina was negatively correlated with another urease-producing genus Bacillus, and had a reciprocal relationship with Atopostipes, which means that the urease-producing microbial community was structurally stable. The enrichment of urease-producing microbial communities in seawater will provide empirical support for the large-scale engineering application of MICP technology in preventing and controlling sandstorms in deserts., 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 © 2022 Elsevier Inc. All rights reserved.)

Several epidemiological studies have shown a clear inverse relationship between serum levels of high-density lipoprotein cholesterol (HDL-C) and the risk of atherosclerotic cardiovascular disease (ASCVD), even at low-density lipoprotein cholesterol levels below 70 mg/dL. There is much evidence from basic and clinical studies that higher HDL-C levels are beneficial, whereas lower HDL-C levels are detrimental. Thus, HDL is widely recognized as an essential anti-atherogenic factor that plays a protective role against the development of ASCVD. Percutaneous coronary intervention is an increasingly common treatment choice to improve myocardial perfusion in patients with ASCVD. Although drug-eluting stents have substantially overcome the limitations of conventional bare-metal stents, there are still problems with stent biocompatibility, including delayed re-endothelialization and neoatherosclerosis, which cause stent thrombosis and in-stent restenosis. According to numerous studies, HDL not only protects against the development of atherosclerosis, but also has many anti-inflammatory and vasoprotective properties. Therefore, the use of HDL as a therapeutic target has been met with great interest. Although oral medications have not shown promise, the developed HDL infusions have been tested in clinical trials and have demonstrated viability and reproducibility in increasing the cholesterol efflux capacity and decreasing plasma markers of inflammation. The aim of the present study was to review the effect of HDL on stent biocompatibility in ASCVD patients following implantation and discuss a novel therapeutic direction of HDL infusion therapy that may be a promising candidate as an adjunctive therapy to improve stent biocompatibility following percutaneous coronary intervention., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Annular rupture is a rare and dreaded complication of transcatheter aortic valve replacement (TAVR) and even rarer when caused by predilatation balloon aortic valvuloplasty. This complication often presents as sudden cardiac tamponade with hypotension and requires urgent intervention. The traditional rescue strategy for patients with annular rupture is emergency surgical repair. However, the mortality rate is still high, considering that most patients who undergo TAVR are not candidates for conventional cardiac surgery. Therefore, there is a need for additional emergency treatment strategies to decrease mortality. This report describes a case of predilatation-induced annular rupture during TAVR that was successfully sealed at the rupture site by valve implantation. This case suggests that continuing with valve deployment may be a successful treatment for predilatation-induced annular rupture during TAVR., (© 2022 Wiley Periodicals LLC.)

Lung cancer is the leading cause of cancer deaths globally, and lung adenocarcinoma (LUAD) is the most common type of lung cancer. Gene dysregulation plays an essential role in the development of LUAD. Drug repositioning based on associations between drug target genes and LUAD target genes are useful to discover potential new drugs for the treatment of LUAD, while also reducing the monetary and time costs of new drug discovery and development. Here, we developed a pipeline based on machine learning to predict potential LUAD-related target genes through established graph attention networks (GATs). We then predicted potential drugs for the treatment of LUAD through gene coincidence-based and gene network distance-based methods. Using data from 535 LUAD tissue samples and 59 precancerous tissue samples from The Cancer Genome Atlas, 48,597 genes were identified and used for the prediction model building of the GAT. The GAT model achieved good predictive performance, with an area under the receiver operating characteristic curve of 0.90. 1,597 potential LUAD-related genes were identified from the GAT model. These LUAD-related genes were then used for drug repositioning. The gene overlap and network distance with the target genes were calculated for 3,070 drugs and 672 preclinical compounds approved by the US Food and Drug Administration. At which, bromoethylamine was predicted as a novel potential preclinical compound for the treatment of LUAD, and cimetidine and benzbromarone were predicted as potential therapeutic drugs for LUAD. The pipeline established in this study presents new approach for developing targeted therapies for LUAD., 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 Huang, Siriwanna, Cho, Wan, Du, Bennett, He, Liu, Huang and Chan.)

Background: Long noncoding RNA colon cancer-associated transcript 1 (LncRNA CCAT1) is highly expressed in gastric cancer tissues and plays a role in autophagy. However, the underlying mechanism still needs to be further clarified., Objective: To study the role of LncRNA CCAT1 in regulating autophagy of gastric cancer cells, analyze its downstream targets, and elucidate the mechanism., Methods: qPCR detected the expression of LncRNA CCAT1 in gastric cancer cells. The proliferation, migration, and invasion ability of LncRNA CCAT1 and the expression level of autophagy-related proteins in gastric cancer cells were detected. Bioinformatics method predicted the downstream targets of LncRNA CCAT1, and they were verified by dual-luciferase assay. The relationship between LncRNA CCAT1, miR-140, and ATG5 was verified by co-transfection, and the expression levels of ATG5 and ATG5-ATG12 complex proteins were detected. Finally, the role of LncRNA CCAT1 in vivo was confirmed by gastric cancer transplantation model., Results: LncRNA CCAT1 was highly expressed in gastric cancer cells. LncRNA CCAT1 can promote the proliferation, migration, invasion, and autophagy activity of gastric cancer cells. LncRNA CCAT1 can bind to miR-140-3p and regulate its expression, while miR-140-3p further regulates the expression of ATG5. Overexpression of LncRNA CCAT1 can promote tumor growth in nude mice. After LncRNA CCAT1 silencing, the positive expression rate of ATG5 in nude mice was low., Conclusion: LncRNA CCAT1 may inhibit the expression of miR-140-3p by sponge adsorption, thus weakening its inhibitory effect on ATG5. Eventually, gastric cancer cells were more prone to autophagy under the pressure of stress., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The sino atrial node (SAN) is characterized by the microenvironment of pacemaker cardiomyocytes (PCs) encased with fibroblasts. An altered microenvironment leads to rhythm failure. Operable cell or tissue models are either generally lacking or difficult to handle. The biological process behind the milieu of SANs to evoke pacemaker rhythm is unknown. We explored how fibroblasts interact with PCs and regulate metabolic reprogramming and rhythmic activity in the SAN., Methods: Tbx18 (T-box transcription factor 18)-induced PCs and fibroblasts were used for cocultures and engineered tissues, which were used as the in vitro models to explore how fibroblasts regulate the functional integrity of SANs. RNA-sequencing, metabolomics, and cellular and molecular techniques were applied to characterize the molecular signals underlying metabolic reprogramming and identify its critical regulators. These pathways were further validated in vivo in rodents and induced human pluripotent stem cell-derived cardiomyocytes., Results: We observed that rhythmicity in Tbx18-induced PCs was regulated by aerobic glycolysis. Fibroblasts critically activated metabolic reprogramming and aerobic glycolysis within PCs, and, therefore, regulated pacemaker activity in PCs. The metabolic reprogramming was attributed to the exclusive induction of Aldoc (aldolase c) within PCs after fibroblast-PC integration. Fibroblasts activated the integrin-dependent mitogen-activated protein kinase-E2F1 signal through cell-cell contact and turned on Aldoc expression in PCs. Interruption of fibroblast-PC interaction or Aldoc knockdown nullified electrical activity. Engineered Tbx18-PC tissue sheets were generated to recapitulate the microenvironment within SANs. Aldoc-driven rhythmic machinery could be replicated within tissue sheets. Similar machinery was faithfully validated in de novo PCs of adult mice and rats, and in human PCs derived from induced pluripotent stem cells., Conclusions: Fibroblasts drive Aldoc-mediated metabolic reprogramming and rhythmic regulation in SANs. This work details the cellular machinery behind the complex milieu of vertebrate SANs and opens a new direction for future therapy.

The purpose of the study was to translate the athlete burnout questionnaire (ABQ) into Simplified Chinese and examine its psychometric properties in Chinese collegiate athletes and elite athletes. Firstly, the factor structure, internal consistency reliability and nomological validity of the Chinese translated ABQ was examined in a sample of Chinese collegiate athletes ( n = 214, 58.9% females). Secondly, abovementioned psychometric properties were examined in a sample of Chinese elite athletes ( n = 505, 52.7% females). Finally, measurement invariance of the Chinese translated ABQ was examined across the two samples. It was found that the 12-item three-correlated-factors model outperformed the one factor model and bi-factor model in collegiate athlete sample whereas the 12-item bi-factor model best represented the factor structure of the Chinese translated ABQ in elite athlete sample. Satisfactory internal consistency reliabilities of the Chinese translated ABQ were evidenced in the two samples. Nomological validity was also supported by the results of the two samples that the three subscales of the ABQ were significantly associated with its theoretically related variables. Results of multiple-group confirmatory factor analysis revealed that weak measurement invariance of the Chinese translated ABQ (three-correlated-factors model) was evidenced across the two samples. Collectively, results of this study indicated that the 12-item Chinese translated ABQ could be used for measuring burnout of Chinese collegiate and elite athletes. Significance and implication of the current study as well as recommendations for future study were discussed., 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 Liu, Wang, Wu, Zou, Jiang, Gao, You, Hu and Liu.)

(1) Background: Coronavirus disease 2019 (COVID-19) is a dominant, rapidly spreading respiratory disease. However, the factors influencing COVID-19 mortality still have not been confirmed. The pathogenesis of COVID-19 is unknown, and relevant mortality predictors are lacking. This study aimed to investigate COVID-19 mortality in patients with pre-existing health conditions and to examine the association between COVID-19 mortality and other morbidities. (2) Methods: De-identified data from 113,882, including 14,877 COVID-19 patients, were collected from the UK Biobank. Different types of data, such as disease history and lifestyle factors, from the COVID-19 patients, were input into the following three machine learning models: Deep Neural Networks (DNN), Random Forest Classifier (RF), eXtreme Gradient Boosting classifier (XGB) and Support Vector Machine (SVM). The Area under the Curve (AUC) was used to measure the experiment result as a performance metric. (3) Results: Data from 14,876 COVID-19 patients were input into the machine learning model for risk-level mortality prediction, with the predicted risk level ranging from 0 to 1. Of the three models used in the experiment, the RF model achieved the best result, with an AUC value of 0.86 (95% CI 0.84-0.88). (4) Conclusions: A risk-level prediction model for COVID-19 mortality was developed. Age, lifestyle, illness, income, and family disease history were identified as important predictors of COVID-19 mortality. The identified factors were related to COVID-19 mortality.

Pacemaker cells can be differentiated from stem cells or transdifferentiated from quiescent mature cardiac cells via genetic manipulation. Here we show that the exposure of rat quiescent ventricular cardiomyocytes to a silk-fibroin hydrogel activates the direct conversion of the quiescent cardiomyocytes to pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin. The silk-fibroin-induced pacemaker cells exhibited functional and morphological features of genuine sinoatrial-node cardiomyocytes in vitro, and pacemaker cells generated via the injection of silk fibroin in the left ventricles of rats functioned as a surrogate in situ sinoatrial node. Biomaterials with suitable surface structure, mechanics and biochemistry could facilitate the scalable production of biological pacemakers for human use., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: This study aimed to investigate the biological impacts and possible mechanisms of a novel lncRNA, LncSIK1, in AML progression and retinoic acid-regulated AML cell development., Materials and Methods: The expression pattern of LncSIK1 was evaluated by qPCR and fluorescence in situ hybridization. CCK-8 assay, immunofluorescence, Wright-Giemsa staining, flow cytometry and Western blotting were performed to assess cell proliferation and differentiation. Bioluminescence imaging and H&E staining were used to detect AML progression in vivo. RNA or chromatin immunoprecipitation assays were conducted to measure the interaction of E2F1 and LncSIK1 or the LC3 and DRAM promoters. Autophagy was measured by transmission electron microscopy and Western blotting., Results: LncSIK1 was silenced in bone marrow mononuclear cells from AML patients compared with those from healthy donors. LncSIK1 strengthened the effect of retinoic acid in inducing cell differentiation and inhibiting cell proliferation in AML cells. Moreover, the silencing of LncSIK1 was critical to maintaining AML leukaemogenesis, as LncSIK1 enhancement retarded AML progression in vivo. Mechanistically, in NB4 cells, LncSIK1 recruited the E2F1 protein to the promoters of LC3 and DRAM and induced autophagy-dependent degradation of the oncoprotein PML-RARa. However, LncSIK1 blocked E2F1 expression and the E2F1-mediated transcription of LC3 and DRAM, thereby relieving aggressive autophagy in Molm13 cells., Conclusions: Taken together, these data indicated that LncSIK1 was an important regulator of AML development through regulating the E2F1/autophagy signalling pathway., (© 2022 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

The clinical use indications for transcatheter aortic valve replacement (TAVR) for the treatment of severe symptomatic aortic stenosis (AS) have expanded from patients at high surgical risk to those at low risk based on the results of multiple large-scale randomized trials. However, patients with bicuspid AS have traditionally been excluded from clinical trials due to their unfavorable morphological characteristics. Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, occurring in 1% to 2% of the total population and affects more than 20% of octogenarians undergoing isolated aortic valve replacement for AS. In recent years, TAVR in patients with bicuspid AS has been the focus of research, especially with respect to the standard of prosthesis size selection. Annulus-based prosthesis size selection using computed tomography (CT) is the standard sizing strategy for tricuspid AS, but no standard sizing for bicuspid AS has been developed thus far. According to Western TAVR experiences, transcatheter heart valve (THV) size selection for BAV patients should be based on the annular structure assessment by CT measurement, whereas Chinese experiences favor adopting the supra-annulus structure assessment for THV size selection. This article will review annular and supra-annular sizing for prosthesis size selection in patients with bicuspid AS before TAVR and discuss which has more favorable clinical outcomes., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Objective: To compare the efficacy and safety of Tonghua Dongbao's insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes. Methods: A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment. Results: For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% ( P <0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % ( P <0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95% CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% ( P =0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% ( P =0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L ( P <0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L ( P <0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group ( P =0.320). Ratios of negative to positive were 7.43% and 10.61% ( P =0.360), and ratios of positive to negative were 10.40% and 7.58% ( P =0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% ( P =0.371), and the incidence of adverse events was 76.60% and 77.70% ( P =0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions: Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.

Microfluidic spinning technology (MST), incorporating microfluidics with chemical reactions, has gained considerable interest for constructing anisotropic advanced microfibers, especially helical microfibers. However, these efforts suffer from the limited material choices, restricting their applications. Here, a new phase inversion-based microfluidic spinning (PIMS) method is proposed for producing helical microfibers. This method undergoes a physicochemical phase inversion process, which is capable of efficiently manufacturing strong (tensile stress of more than 25 MPa), stretchable, flexible and biocompatible helical microfibers. The helical microfibers can be used to fabricate bi-oriented stretchable artificial abdominal skin, preventing incisional hernia formation and promoting the wound healing without conglutination. This research not only offers a universal approach to design helical microfibers but also provides a new insight into artificial skin., (© 2021 Wiley-VCH GmbH.)

The MinION nanopore sequencing device (Oxford Nanopore Technologies, Oxford, UK) is the smallest commercially available sequencer and can be used outside of conventional laboratories. The use of the MinION for forensic applications, however, is hindered by the high error rate of nanopore sequencing. One approach to solving this problem is to identify forensic genetic markers that can consistently be typed correctly based on nanopore sequencing. In this pilot study, we explored the use of nanopore sequencing for single nucleotide polymorphism (SNP) and short tandem repeat (STR) profiling using Verogen's (San Diego, CA, USA) ForenSeq DNA Signature Prep Kit. Thirty single-contributor samples and DNA standard material 2800 M were genotyped using the Illumina (San Diego, CA, USA) MiSeq FGx and MinION (with R9.4.1 flow cells) devices. With an optimized cutoff for allelic imbalance, all 94 identity-informative SNP loci could be genotyped reliably using the MinION device, with an overall accuracy of 99.958% (1 error among 2926 genotypes). STR typing was notably error prone, and its accuracy was locus dependent. We developed a custom-made bioinformatics workflow, and finally selected 13 autosomal STRs, 14 Y-STRs, and 4 X-STRs showing high consistency between nanopore and Illumina sequencing among the tested samples. These SNP and STR loci could be candidates for panel design for forensic analysis based on nanopore sequencing., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To describe patient characteristics associated with preoperative anxiety and subsequently assess the relationship between preoperative anxiety and postoperative anxiety, pain, sleep quality, nausea and vomiting., Methods: The study collected data from patients undergoing elective operation from 12 hospitals in China. The State-Trait Anxiety Inventory (STAI) and the Athens Insomnia Scale (AIS) were used to assess anxiety and sleep quality before surgery. Evaluations of anxiety, pain, sleep quality, nausea and vomiting were quantified using the Visual Analogue Scale on postoperative days 1 and 2., Results: Data from 997 patients were analyzed. Preoperatively, 258 (25.9%) patients had high anxiety (STAI-State>44). Multivariate analyses showed a significant relationship between high anxiety and female gender (OR: 1.66, 95% CI: 1.08-2.57, p = 0.02), highly invasive surgery (OR: 2.29, 95% CI: 1.29-4.06, p = 0.005), higher trait anxiety (OR: 1.24, 95% CI: 1.20-1.28, p < 0.001) and insomnia (AIS ≥ 6, OR: 1.79, 95% CI: 1.17-2.76, p = 0.008). Preoperative anxiety demonstrated a negative correlation with postoperative anxiety following highly invasive surgery; this became a positive relationship following less invasive surgery. Preoperative anxiety was also positively related to postoperative pain and poor sleep quality. The correlation between preoperative anxiety and postoperative nausea and vomiting was not statistically significant., Conclusion: Female gender, highly invasive surgery, higher trait anxiety and insomnia are independent risk factors for high preoperative anxiety. Surgical invasiveness influences association between pre- and postoperative anxiety. Higher preoperative anxiety is related to poorer sleep quality and more severe pain postoperatively., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this article, a decentralized adaptive finite-time tracking control scheme is proposed for a class of nonstrict feedback large-scale nonlinear interconnected systems with disturbances. First, a practical almost fast finite-time stability framework is established for a general nonlinear system, which is then applied to the design of the large-scale system under consideration. By fusing command filter technique and adaptive neural control and introducing two smooth functions, the "singular" and "explosion of complex" problems in the backstepping procedure are circumvented, while the obstacles caused by unknown interconnections are overcome. Moreover, according to the framework of practical almost fast finite-time stability, it is shown that all the closed-loop signals of the large-scale system are almost fast finite-time bounded, and the tracking errors can converge to arbitrarily small residual sets predefined in an almost fast finite time. Finally, a simulation example is presented to demonstrate the effectiveness of the proposed finite-time decentralized control scheme.

Objective: To explore the effect and related regulatory mechanism of hawthorn leaf flavonoids (FHL) on cardiac function in rats with acute myocardial infarction (AMI). Methods: Sixty SPF male Sprague-Dawley rats (9-week-old, weighing 300-350 g) were used in this study. Ten rats were assigned to sham operation group, and the remaining 50 rats were used to establish the AMI model with coronary artery ligation method, AMI was successfully established in 36 rats. AMI rats were randomly divided into AMI group and FHL low-, medium-, and high-dose groups ( n =9 for each group). Rats received intraperitoneal injection (10 ml·kg -1 ·day -1 ) with physiological saline and FHL solution with concentrations of 0.3, 0.6, and 1.2 mg/ml, respectively for 4 consecutive weeks. Echocardiography was performed at the end of experiments. Left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic anterior wall thickness (LAWD), left ventricular ejection fraction (LVEF) and left ventricular end diastolic pressure (LVEDP) were measured. Then the rats were sacrificed under deep anesthesia, and the left ventricular anterior wall tissue was used for pathological examinations by hematoxylin-eosin (HE) staining. Other myocardial tissue was used for in situ terminal transferase labeling (TUNEL) staining, and the apoptosis rate of cardiomyocytes was calculated. The myocardial cell apoptosis rate, the mRNA, and protein expressions of phosphatidylinositol 3β-kinase (PI3K), protein kinase B (Akt), glycogen synthetase kinase-3 (GSK3β), cyclin D1 and the protein expressions of p-Akt and p-GSK3β were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot respectively. Results: Compared with sham operation group, the LVEDD and LVEDP of the rats in AMI group and FHL low-, medium-and high-dose groups were increased, and the LAWD and LVEF were reduced (all P <0.05). Compared with AMI group, LVEDD and LVEDP were reduced, and LAWD and LVEF were increased in FHL low-, medium-and high-dose groups (all P <0.05). LVEDD and LVEDP decreased, and LAWD and LVEF increased in proportion to the increase of FHL dose (all P <0.05). LVEDD and LAWD values were similar between FHL low-dose and medium-dose groups (both P >0.05). HE staining results evidenced necrotic myocardial tissue, together with disordered arrangement of myocardial fibers, and a large number of inflammatory cells infiltrated in the myocardial tissue in AMI group. The myocardial damage of rats in FHL low-, medium-, and high-dose groups was less than that of AMI group. The myocardial fibers were arranged neatly, but there were still partial breaks and a small amount of inflammatory cell infiltration in the myocardial tissue and there were scattered islands of normal myocardial tissue in the infarct area of these groups. Among them, myocardial damage was the least in FHL high-dose group. The results of TUNEL staining showed that compared with AMI group, the apoptosis rate of myocardial cells was significantly reduced in FHL low-, medium-, and high-dose groups (all P <0.001), but was still higher than that in sham operation group (all P <0.001). Myocardial cell apoptosis rate decreased in proportion with increasing FHL dose ( P <0.05). The RT-qPCR results showed that compared with AMI group, the expression levels of PI3K and cyclin D1 mRNA were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P <0.05), and PI3K and cyclin D1 mRNA expression levels increased with the increase dose of FHL ( P <0.05). Western blot results showed that compared with AMI group, the expression levels of PI3K, p-Akt, p-GSK3β, and cyclin D1 were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P <0.05), and the protein expression levels of PI3K, p-Akt, p-GSK3β, and cyclin D1 increased in proportion with the increase dose of FHL (all P <0.05). Conclusion: FHL can effectively improve cardiac function in rats with AMI, and the beneficial effects may be partly mediated through activating PI3K/GSK3β/cyclin D1 signaling pathway.

The Chinese mitten crab is an important economic species in the Chinese aquaculture industry due to its rich nutritional value and distinct flavor. The hepatopancreas is a popular edible part of the Chinese mitten crab, and therefore, hepatopancreatic health directly determines its quality. However, a large-scale outbreak of hepatopancreatic necrosis syndrome ("Shuibiezi" disease in Chinese), which is caused by abiotic agents correlated with cyanobacteria bloom outbreaks, adversely affects the Chinese mitten crab breeding industry. Cyanobacterial blooms that occur in high-density farming ponds can produce microcystin-LR (MC-LR), which is hepatotoxic in fish and mammals. Hepatopancreas toxicity of MC-LR (0, 25, 50 and 75 μg/kg) was investigated after 48 h of exposure. The MC-LR can cause hepatopancreatic injury by inducing hepatopancreatic structural damage, subcellular structural changes, and cell apoptosis, followed by enhanced lipid peroxidase, reactive oxygen species, and apoptosis-related enzyme (Caspase 3, 8, and 9) activities. These in turn promote gene and protein expression of apoptosis-associated proteases (Caspase 3, 7, and 8, Bcl-2, and Bax), and alter antioxidant system responses (superoxide dismutase, glutathione S-transferase, glutathione peroxidase, glutathione reductase activities, and glutathione content). The present study is the first report on MC-LR hepatotoxicity in the Chinese mitten crab and confirms hepatopancreas toxicity, providing a theoretical basis for enhancing MCs resistance and developing preventive and curative measures against hepatopancreatic disease in the Chinese mitten crab breeding industry.

Exploring the characteristics of soil seed bank under seasonal grazing plays an important role in the reasonable use of desert steppe. We examined seed bank species composition, density, vertical distribution, diversity in the soil of 0-5, 5-10, 10-15 cm soil layers and the relationship with vegetation and soil environmental factors in Ningxia desert steppe. The treatments included enclosure (FY), traditional time rotation grazing (FG), delayed to start rotation grazing (YG), early to end rotation grazing (TG), delayed to start and early to end rotation grazing (YT) and free grazing (ZY). The results showed that there were nine families and 21 species in the soil seed bank in the study area. The species composition of soil seed bank in TG seed bank with 13 species was the largest, while FY and ZY soil seed banks had the least, with 8 species, respectively. The den-sity of ZY soil seed bank was significantly higher than that of FY, YG, TG and YT. The number of perennial species seeds in the soil seed bank of FY was the largest, reaching 32.0%, while that in the ZY was the least, only 12.4%, mainly with sexually reproduced annual weeds. Soil seed bank was mainly concentrated in the 0-5 cm surface layer. With increasing soil depth, the size of soil seed bank decreased. The dominance and diversity of soil seed bank were the highest in FY, while the dominance, diversity and uniformity were the lowest in ZY. The similarity between soil seed bank and aboveground vegetation was generally low. In contrast, the FG and ZY seed banks had higher similarity with vegetation, and the FY was the lowest. Soil moisture, organic matter, total nitrogen concentration, total phosphorus concentration, and soil bulk density were the main soil factors affecting soil seed bank. Compared with traditional whole year free grazing, seasonal four-zone rotation grazing could increase species richness and abundance of perennial plants in soil seed bank of desert steppe, as well as the total species richness, diversity and uniformity of the seed bank. Although the effect sof seasonal four-zone rotation grazing on seed bank was not as good as the long-term enclosure grassland, it was of great significance to the utilization and protection of desert steppe.

Objective: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL32) and "Huiyang" (BL35) on the expression of extracellular signal-regulated kinase 1/2 (p-ERK1/2) and cellular oncogene fos (c-fos) phosphorylated of spinal dorsal horn in rats with interstitial cystitis (IC)., Methods: Eighteen female Wistar rats were randomly divided into control, model and EA groups, with 6 rats in each group. The IC model was established by intraperitoneal injection of cyclophosphamide (150 mg/kg). EA (30 Hz, 1 mA) was applied to bilateral BL32 and BL35 for 20 min, once daily for 3 consecutive days. The bladder pain was measured by using a Von Frey at 48 h after modeling and 24 h after EA. The expression levels of p-ERK1/2 and c-fos protein in L6-S1 segment of spinal cord were detected by Western blot, and the expression of p-ERK1/2 and c-fos in the right spinal dorsal horn were displayed by immunofluorescence staining., Results: After modeling, the bladder mechanical pain threshold (PT) was significantly decreased ( P <0.05), the protein expression of p-ERK1/2 and c-fos in the spinal cord was increased ( P <0.05) and the immunofluorescence surface density of p-ERK1/2 and c-fos in the right dorsal horn of spinal cord was increased ( P <0.05) in the model group relevant to the control group. After EA intervention, IC-induced reduction of PT, and increases of the expression of p-ERK1/2 and c-fos as well as immunofluorescence surface density of p-ERK1/2 and c-fos were reversed in the EA group relevant to the model group ( P <0.05)., Conclusion: EA at BL 32 and BL 35 has an analgesic effect in IC rats, which may be related to its effect in down-regulating the expression of p-ERK1/2 and c-fos in spinal dorsal horn.

Calixarenes, with potential functionalization on the upper and lower rim, have been explored in recent years for the design and construction of anticancer agents in the field of drugs and pharmaceuticals. Herein, optimization of bis [N-(2-hydroxyethyl) aminocarbonylmethoxyl substituted calix [4] arene (CLX-4) using structure-based drug design and traditional medicinal chemistry led to the discovery of series of calix [4]arene carbonyl amide derivatives 5a-5t. Evaluation of the cytotoxicity of 5a-5t employing MTT assay in MCF-7, MDA-MB-231 (human breast cancer cells), HT29 (human colon carcinoma cells), HepG2 (human hepatocellular carcinoma cells), A549 (human lung adenocarcinoma cells) and HUVEC (Human Umbilical Vein Endothelial) cells demonstrated that the most promising compound 5h displayed the most superior inhibitory effect against A549 and MDA-MB-231 cells, which were 3.2 times and 6.8 times of CLX-4, respectively. In addition, the cell inhibition rate (at 10 μM) against normal HUVEC cells in vitro was only 9.6%, indicating the safty of compound 5h. Moreover, compound 5h could inhibit the migration of MDA-MB-231 cell in wound healing assay. Further mechanism studies significantly indicated that compound 5h could block MDA-MB-231 cell cycle arrest in G0/G1 phase by down regulating cyclin D1 and CDK4, and induce apoptosis by up-regulation of Bax, down-regulation of Caspase-3, PARP and Bcl-2 proteins, resulting in the reduction of DNA synthesis and cell division arrest. This work provides worthy of further exploration for the promising calixarene-based anticancer drugs., 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 Masson SAS. All rights reserved.)