Publications by authors named "Lijun Wang"

993 Publications

Internet of things-enabled real-time health monitoring system using deep learning.

Neural Comput Appl 2021 Sep 15:1-12. Epub 2021 Sep 15.

Hankuk University of Foreign Studies, Yongin-si, Republic of Korea.

Smart healthcare monitoring systems are proliferating due to the Internet of Things (IoT)-enabled portable medical devices. The IoT and deep learning in the healthcare sector prevent diseases by evolving healthcare from face-to-face consultation to telemedicine. To protect athletes' life from life-threatening severe conditions and injuries in training and competitions, real-time monitoring of physiological indicators is critical. In this research work, we present a deep learning-based IoT-enabled real-time health monitoring system. The proposed system uses wearable medical devices to measure vital signs and apply various deep learning algorithms to extract valuable information. For this purpose, we have taken Sanda athletes as our case study. The deep learning algorithms help physicians properly analyze these athletes' conditions and offer the proper medications to them, even if the doctors are away. The performance of the proposed system is extensively evaluated using a cross-validation test by considering various statistical-based performance measurement metrics. The proposed system is considered an effective tool that diagnoses dreadful diseases among the athletes, such as brain tumors, heart disease, cancer, etc. The performance results of the proposed system are evaluated in terms of precision, recall, AUC, and F1, respectively.
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http://dx.doi.org/10.1007/s00521-021-06440-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442525PMC
September 2021

Application of neurally adjusted ventilatory assist in ventilator weaning of infants ventilator weaning.

Brain Behav 2021 Sep 14:e2350. Epub 2021 Sep 14.

Department of Pediatric Critical Medicine, Maternal and Child Health Care Hospital of Hubei Province, Wuhan, China.

Background: To analyze the application of neurally adjusted ventilatory assist in ventilator weaning of infants.

Methods: A total of 25 infants (15 boys and 10 girls) who were mechanically ventilated by PICU in Hubei Maternal and Child Health Hospital were selected as the study subjects. After the improvement of the basic disease, regular spontaneous breathing, and the withdrawal of the ventilator, all the children obtained the electrical activity of the diaphragm (EAdi) signal. Then, each child was given CPAP and NAVA mode mechanical ventilation 1 h before the withdrawal of the ventilator. Each detection index was recorded 30 min after each mode of ventilation.

Results: Two of the 25 children were tracheotomized because of respiratory muscle weakness and could not be converted to NAVA mode without the EAdi signal. Hemodynamic indexes were not statistically different between the two groups of CPAP and NAVA. PaCO is not significantly different in the two modes, and both were at normal levels. The PIP in NAVA mode is lower than that in CPAP mode (p < .05), and its EAdi signal was correspondingly low. There were significant differences in the peak pressure (Ppeak), mean pressure (Pmean), and compliance and mean arterial pressure (p < .01) between the CPAP and NAVA model ventilation in 23 patients.

Conclusion: NAVA can significantly improve the coordination of patients. The therapeutic effect of NAVA was better, which was beneficial to the prognosis of patients and had positive application value in the withdrawal of ventilators in patients.
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http://dx.doi.org/10.1002/brb3.2350DOI Listing
September 2021

A sensitive aptasensor based on rolling circle amplification and G-rich ssDNA/terbium (III) luminescence enhancement for ofloxacin detection in food.

Talanta 2021 Dec 4;235:122783. Epub 2021 Aug 4.

School of Food and Biological Engineering, Xihua University, Chengdu, 610039, China; Key Laboratory of Food Non Thermal Processing, Engineering Technology Research Center of Food Non Thermal Processing, Yibin Xihua University Research Institute, Yibin, Sichuan, 644004, China. Electronic address:

As the light-harvesting "antenna", G-rich oligonucleotides (such as the G-quadruplex) can interact with lanthanide (III) to bring a luminescent enhancement response. In this study, phenomenon of luminescent enhancement of G-triplex/terbium (III) (G3/Tb) and interaction between G3 and Tb were first reported and characterized. Based on G3/Tb luminescence, a label-free aptasensor for the detection of ofloxacin (OFL) residues in the food was developed. The OFL triggered the action of rolling circle amplification (RCA) allowed for the amplification product of G3-forming sequences in the single-stranded DNA, which promoted the conformational transition of the G3/Tb complexes once the addition of Tb. Under the optimal conditions, the logarithmic correlation between the G3/Tb luminescence intensity and the concentration of OFL was found to be linear in the range of 5-1000 pmol L (R = 0.9949). The limit of detection was 0.18 pmol L (3σ/slope). Additionally, the good recoveries of 90.19-108.89 % and the relative standard deviations values of 0.59-5.87 % were obtained in the application of the aptasensor detecting OFL in the practical samples. These results confirmed that the present aptasensor has a good analytical performance and bright prospect for detecting ofloxacin residues in food.
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http://dx.doi.org/10.1016/j.talanta.2021.122783DOI Listing
December 2021

Long non-coding RNA MALAT1 enhances the protective effect of dexmedetomidine on acute lung injury by sponging miR-135a-5p to downregulate the ratio of X-box binding proteins XBP-1S/XBP-1U.

Bioengineered 2021 Dec;12(1):6377-6389

Department of Anesthesiology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Acute lung injury (ALI) is the common and clinically severe complication. Dexmedetomidine (DEX) can protect against lipopolysaccharide (LPS)-induced ALI through anti-apoptosis, anti-inflammatory and immune regulatory actions. It is well documented that major causes of LPS-induced ALI are endoplasmic reticulum stress (ERS) and abnormally elevated CHOP. Moreover, XBP-1 can enhance CHOP expression. XBP-1S can aggravate ERS and XBP-1 U can repress ERS. By querying Starbase, miR-135a-5p interacts with XBP-1 and lncRNA MALAT1 sponges miR-135a-5p. It has been reported that MALAT1 interference markedly promoted the apoptosis of pulmonary microvascular endothelial cells in ALI rats by activating TLR4/NF-κB pathway. miR-135a-5p inhibitor remarkably alleviated LPS-induced A549 cell injury through suppressing cell apoptosis. In the present work, LPS was dripped into the nasal cavity of SD rats to establish the rat model of ALI and LPS was also applied to stimulate BEAS-2B cells to imitate ALI . Then, the pathology, lung function indexes, levels of inflammatory factors, apoptosis of lung tissues in SD rats and apoptotic level of BEAS-2B cells were measured, so as to confirm whether upregulation of lncRNA MALAT1 was able to suppress ERS, thus enhancing the protective effect of DEX against ALI. Herein, overexpression of lncRNA MALAT1 strengthened the remission effects of DEX on LPS-triggered ALI, severe pulmonary edema, inflammatory response and cell apoptosis of lung tissues in SD rats and reinforced the anti-apoptosis effect of DEX on LPS-stimulated BEAS-2B cells. Mechanically, lncRNA MALAT1 enhanced the protective effect of DEX against ALI by downregulating the ratio of XBP-1S/XBP-1U to repress ERS.
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http://dx.doi.org/10.1080/21655979.2021.1967579DOI Listing
December 2021

MODB: a comprehensive mitochondrial genome database for Mollusca.

Database (Oxford) 2021 Sep;2021

College of Life Sciences, Yantai University, No.30 Qingquan Road, Laishan District, Yantai, Shandong 264005, China.

Mollusca is the largest marine phylum, comprising about 23% of all named marine organisms, Mollusca systematics are still in flux, and an increase in human activities has affected Molluscan reproduction and development, strongly impacting diversity and classification. Therefore, it is necessary to explore the mitochondrial genome of Mollusca. The Mollusca mitochondrial database (MODB) was established for the Life and Health Big Data Center of Yantai University. This database is dedicated to collecting, sorting and sharing basic information regarding mollusks, especially their mitochondrial genome information. We also integrated a series of analysis and visualization tools, such as BLAST, MUSCLE, GENEWISE and LASTZ. In particular, a phylogenetic tree was implemented in this database to visualize the evolutionary relationships between species. The original version contains 616 species whose mitochondrial genomes have been sequenced. The database provides comprehensive information and analysis platform for researchers interested in understanding the biological characteristics of mollusks. Database URL: http://modb.ytu.edu.cn/.
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http://dx.doi.org/10.1093/database/baab056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435058PMC
September 2021

Peony seed oil ameliorates neuroinflammation-mediated cognitive deficits by suppressing microglial activation through inhibition of NF-κB pathway in presenilin 1/2 conditional double knockout mice.

J Leukoc Biol 2021 Sep 8. Epub 2021 Sep 8.

Department of Physiology, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Chronic neuroinflammation has been shown to exert adverse influences on the pathology of Alzheimer's disease (AD), associated with the release of abundant proinflammatory mediators by excessively activated microglia, causing synaptic dysfunction, neuronal degeneration, and memory deficits. Thus, the prevention of microglial activation-associated neuroinflammation is important target for deterring neurodegenerative disorders. Peony seed oil (PSO) is a new food resource, rich in α-linolenic acid, the precursor of long chain omega-3 polyunsaturated fatty acids, including docosahexaenoic acid and eicosapentaenoic acid, which exhibit anti-inflammatory properties by altering cell membrane phospholipid fatty acid compositions, disrupting lipid rafts, and inhibiting the activation of the proinflammatory transcription factor NF-κB. However, few studies have examined the anti-neuroinflammatory effects of PSO in AD, and the relevant molecular mechanisms remain unclear. Presenilin1/2 conditional double knockout (PS cDKO) mice display obvious AD-like phenotypes, such as neuroinflammatory responses, synaptic dysfunction, and cognitive deficits. Here, we assessed the potential neuroprotective effects of PSO against neuroinflammation-mediated cognitive deficits in PS cDKO using behavioral tests and molecular biologic analyses. Our study demonstrated that PSO suppressed microglial activation and neuroinflammation through the down-regulation of proinflammatory mediators, such as inducible NOS, COX-2, IL-1β, and TNF-α, in the prefrontal cortex and hippocampus of PS cDKO mice. Further, PSO significantly lessened memory impairment by reversing hyperphosphorylated tau and synaptic proteins deficits in PS cDKO mice. Importantly, PSO's therapeutic effects on cognitive deficits were due to inhibiting neuroinflammatory responses mediated by NF-κB signaling pathway. Taken together, PSO may represent an effective dietary supplementation to restrain the neurodegenerative processes of AD.
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http://dx.doi.org/10.1002/JLB.3MA0821-639RRDOI Listing
September 2021

Pneumonitis, appendicitis, and biliary obstruction during toripalimab treatment in a patient with extensive-stage small-cell lung cancer: a case report.

Ann Palliat Med 2021 Aug;10(8):9267-9275

Department of Thoracic Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.

In recent years, immune checkpoint inhibitors (ICIs) have become a standard treatment for patients with advanced lung cancers. With the widespread use of immunotherapy in clinical practice, immune-related adverse events (irAEs) have become increasingly common. This case report details a 72-year-old man with small-cell lung cancer (SCLC) who developed pneumonitis, appendicitis, and biliary obstruction during treatment with toripalimab. The patient was initially diagnosed with limited-stage SCLC in January 2019 and completed 5 sequential cycles of etoposide/cisplatin (EP) and radiotherapy (60 Gy/30 F). The overall response was complete response (CR) after first line treatment. He developed radiation pneumonitis after completion of radiotherapy, which responded well to symptomatic treatment. Due to newly diagnosed bone metastasis, he was administered toripalimab intravenously every 3 weeks and 12 mg anlotinib orally once a day from January 2020. By the third cycle, the patient presented with electrocardiographic abnormalities, gingival swelling and pain, and hoarseness, and consequently, the anlotinib was suspended. After 4 cycles, he developed suppurative appendicitis, which was managed successfully with anti-inflammatory agents. He then presented with shortness of breath on exertion and after a comprehensive examination, he was diagnosed with ICI-related-pneumonitis. After 6 weeks of treatment with methylprednisolone, the shortness of breath was mostly relieved and treatment continued. In June 2020, the patient developed severe vomiting. Computed tomography (CT) indicated biliary obstruction, and at endoscopic retrograde cholangiopancreatography (ERCP) there was edema of the major papilla of the duodenum. The patient's symptoms were relieved after treatment with gastric acid suppression and antiemetics. Re-examination by magnetic resonance imaging (MRI) showed that the biliary obstruction had been resolved. Although the disease progressed after immunotherapy, no tumor tissue related to the biliary obstruction was detected, and this was therefore classified as an irAE.
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http://dx.doi.org/10.21037/apm-21-858DOI Listing
August 2021

Exploration of immune-related cells and ceRNA in squamous cell lung cancer.

Medicine (Baltimore) 2021 Sep;100(35):e27058

Department of Respiratory Oncology, Anhui Provincial Cancer Hospital (The First Affiliated Hospital of USTC West District), Hefei.

Abstract: The treatment for squamous cell lung cancer (SqCLC) is limited, and the prognosis of SqCLC is poor. In this article, we aimed to analyze and identify immune-related cells and competition endogenous RNA (ceRNA) that influence the prognosis of SqCLC. SqCLC and lung adenocarcinoma data were downloaded from TCGA-GDC. A total of 22 types of immune cell fractions were estimated using CIBERSORT. R software was used to identify any significantly different transcriptome data, including mRNA, LncRNA, and miRNA. The univariate cox regression method was applied to screen for prognosis-related lncRNA, miRNA, mRNA and tumor-infiltrating immune cells. There were 504 patients included in this study. There was a higher proportion of memory activated CD4+ T cells and CD8+ T cells in younger women. Follicular helper T (Tfh) cells were predictive of a good prognosis and reflected immune activation in SqCLC. The SFTA1P/NKX2-1-AS1, hsa-mir-503, GREM2 ceRNA axes and NKX2-1-AS1, hsa-mir-96, PROK2 ceRNA axes were found to be important for the immune function, pathogenesis, and prognosis of SqCLC. Collectively, the immune-related ceRNA and tumor-infiltrating immune cells in SqCLC are likely important determinants of SqCLC pathogenesis, prognosis, and immune status.
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http://dx.doi.org/10.1097/MD.0000000000027058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415993PMC
September 2021

Mortality and years of life lost of cardiovascular diseases in China, 2005-2020: Empirical evidence from national mortality surveillance system.

Int J Cardiol 2021 Oct 26;340:105-112. Epub 2021 Aug 26.

National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address:

Objectives: Cardiovascular disease (CVD) is leading cause of death in China. We aimed to provide national and subnational estimates and its change of premature mortality burden of CVD during 2005-2020.

Methods: Data from multi-source on the basis of national mortality surveillance system (NMSS) was used to estimate mortality and years of life lost (YLL) of total CVD and its subcategories in Chinese population across 31 provinces during 2005-2020.

Results: Estimated CVD deaths increased from 3.09 million in 2005 to 4.58 million in 2020; the age-standardized mortality rate (ASMR) decreased from 286.85 per 100,000 in 2005 to 245.39 per 100,000 in 2020. A substantial reduction of 19.27% of CVD premature mortality burden, as measured by age-standardized YLL rate, was observed. Ischemic heart disease (IHD), hemorrhagic stroke (HS) and ischemic stroke (IS) were leading 3 causes of CVD death. Marked differences were observed in geographical patterns for total CVD and its subcategories, and it appeared to be lower in areas with higher economic development. Population ageing was dominant driver contributed to CVD deaths increase, followed by population growth. And, age-specific mortality shifts contributed largely to CVD deaths decline in most provinces.

Conclusion: Substantial discrepancies were demonstrated in CVD premature mortality burden across China. Targeted considerations were needed to integrate primary care with clinical care through intensifying further strategies for reducing CVD mortality among specific subcategories, high risk population and regions with inadequate healthcare resources.
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http://dx.doi.org/10.1016/j.ijcard.2021.08.034DOI Listing
October 2021

Sentinel lymph node mapping in early-stage cervical cancer: Meta-analysis.

Medicine (Baltimore) 2021 Aug;100(34):e27035

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.

Background: The value of sentinel lymph node (SLN) mapping for early-stage cervical cancer remains controversial. Therefore, we collected data to investigate the feasibility and diagnostic accuracy of SLN in patients with early-stage (IA-IIA) cervical cancer.

Methods: We searched Embase, PubMed, and the Cochrane Library databases issued before June 1, 2020. The sample size of the selected study was at least 10 patients with early-stage (IA-IIA) cervical cancer, the pooled detection rates and the separate detection rate (overall detection rate, bilateral detection rate) using blue dye with Tc, technetium 99 (Tc) and indocyanine green (ICG) technique of early-stage cervical cancer was reported. R-3.6.1 software was used to evaluate pooled detection rate and sensitivity.

Results: Two thousand one hundred sixty-four patients included for analysis in 28 studies ranging from 12 to 405 patients. The combined overall detection rate of SLN mapping was 95% with a 72% pooled bilateral detection rate. The sensitivity of the combined overall detection rate of SLN mapping was 94.99% as well as a sensitivity of 72.43% bilateral detection rate. The overall detection rate of SLN was 96% for blue dye with Tc, 95% for Tc, 98% for ICG technique. The bilateral detection rate of SLN was 76% for blue dye with Tc, 63% for Tc, 85% for ICG technique. The sensitivity of the overall detection rate of SLN mapping was 97.76% as well as a sensitivity of 84.96% bilateral detection rate of ICG technique.

Conclusion: In early-stage cervical cancer, overall detection rate of SLN mapping is elevated while bilateral detection rate is lower. The overall detection rate (98%) as well as bilateral rate (85%) of ICG seems to be a better SLN mapping technique among the method of SLN mapping (using blue dye with Tc, Tc or ICG). We believe SLN mapping may be considered contemporary technique which could provide additional benefits over traditional pelvic lymphadenectomy. While promising results in SLN mapping has been found, larger patient samples, including randomized studies, are required at the same time.
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http://dx.doi.org/10.1097/MD.0000000000027035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389869PMC
August 2021

Use patterns of cigarettes and alternative tobacco products and socioeconomic correlates in Hong Kong secondary school students.

Sci Rep 2021 Aug 26;11(1):17253. Epub 2021 Aug 26.

School of Nursing, University of Hong Kong, Hong Kong, People's Republic of China.

Smoking is a major cause of health inequities. However, sociodemographic differences in adolescent tobacco use are unclear. In a territory-wide school-based anonymous survey in 2018/19, we investigated tobacco use and sociodemographic correlates in 33,991 students (mean age 14.8 ± 1.9 years) in Hong Kong. Tobacco use prevalence and current-ever use ratios by sociodemographic factors were calculated. Generalised linear mixed models were used in association analyses. Current use was highest for cigarettes (3.2%), closely followed by alternative tobacco products (3.0%). Current-ever use ratios were highest for heated tobacco products (HTPs, 0.60), followed by nicotine e-cigarettes (0.52), waterpipe (0.51), and cigarettes (0.35). Use prevalence and current-ever use ratios of all products showed curvilinear relations with perceived family affluence (P values < 0.01), being highest in the richest families. Tobacco use was also associated with more senior grades, the lowest parental education, and boys, but current-ever use ratios of HTPs and waterpipe were higher in girls (P values < 0.05). The results suggested that adolescent ever users of nicotine-containing alternative tobacco products were more likely to keep using them than cigarettes, and the richest adolescents were at the highest risks of tobacco use. Diverse tobacco control measures are needed to improve health equity, especially on alternative tobacco products.
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http://dx.doi.org/10.1038/s41598-021-96452-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390664PMC
August 2021

Oligomerization of Selective Autophagy Receptors for the Targeting and Degradation of Protein Aggregates.

Cells 2021 Aug 5;10(8). Epub 2021 Aug 5.

Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

The selective targeting and disposal of solid protein aggregates are essential for cells to maintain protein homoeostasis. Autophagy receptors including p62, NBR1, Cue5/TOLLIP (CUET), and Tax1-binding protein 1 (TAX1BP1) proteins function in selective autophagy by targeting ubiquitinated aggregates through ubiquitin-binding domains. Here, we summarize previous beliefs and recent findings on selective receptors in aggregate autophagy. Since there are many reviews on selective autophagy receptors, we focus on their oligomerization, which enables receptors to function as pathway determinants and promotes phase separation.
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http://dx.doi.org/10.3390/cells10081989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394947PMC
August 2021

AGTR1 blocker attenuates activation of Tenon's capsule fibroblasts after glaucoma filtration surgery via the NF-κB signaling pathway.

Exp Cell Res 2021 Oct 17;407(1):112786. Epub 2021 Aug 17.

Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an, 710004, China. Electronic address:

Activation of Tenon's capsule fibroblasts limits the success rate of glaucoma filtration surgery (GFS), the most efficacious therapy for patients with glaucoma. Angiotensin type 1 receptor (AGTR1) is involved in tissues remodeling and fibrogenesis. However, whether AGTR1 is involved in the progress of fibrogenesis after GFS is not fully elucidated. The aim of this study was to investigate the role of an AGTR1 in scar formation after GFS and the potential anti-fibrosis effect of AGTR1 blocker. AGTR1 expression level was increased in subconjunctival tissues in a rat model of GFS and transforming growth factor-beta 2 (TGF-β2)-induced human Tenon's capsule fibroblasts (HTFs). AGTR1 blocker treatment suppressed TGF-β2-induced HTF migration and α-smooth muscle actin (α-SMA) and fibronectin (FN) expression. AGTR1 blocker treatment also attenuated collagen deposition and α-SMA and FN expression in subconjunctival tissues of the rat model after GFS. Moreover, AGTR1 blocker decreased TGF-β2-induced P65 phosphorylation, P65 nuclear translocation, and nuclear factor kappa B (NF-κB) luciferase activity. Additionally, BAY 11-7082 (an NF-κB inhibitor) significantly suppressed HTF fibrosis. In conclusion, our results indicate that AGTR1 is involved in scar formation after GFS. The AGTR1 blocker attenuates subconjunctival fibrosis after GFS by inhibiting the NF-κB signaling pathway. These findings indicate that targeting AGTR1 is a potential approach to attenuate fibrosis after GFS.
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http://dx.doi.org/10.1016/j.yexcr.2021.112786DOI Listing
October 2021

Wearable Device-Based Smart Football Athlete Health Prediction Algorithm Based on Recurrent Neural Networks.

J Healthc Eng 2021 30;2021:2613300. Epub 2021 Jul 30.

Institute of Physical Education and Health, Yulin Normal University, Yulin 537000, China.

For football players who participate in sports, the word "health" is extremely important. Athletes cannot create their own value in competitive competitions without a strong foundation. Scholars have paid a lot of attention to athlete health this year, and many analysis methods have been proposed, but there have been few studies using neural networks. As a result, this article proposes a novel wearable device-based smart football player health prediction algorithm based on recurrent neural networks. To begin, this article employs wearable sensors to collect health data from football players. The time step data are then fed into a recurrent neural network to extract deep features, followed by the health prediction results. The collected football player health dataset is used in this paper to conduct experiments. The simulation results prove the reliability and superiority of the proposed algorithm. Furthermore, the algorithm presented in this paper can serve as a foundation for the football team's and coaches' scientific training plans.
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http://dx.doi.org/10.1155/2021/2613300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349259PMC
July 2021

Value of layer-specific speckle tracking echocardiography for early detection of myocardial injury caused by chemotherapy in breast cancer patients with cardiovascular risk.

Int J Cardiovasc Imaging 2021 Aug 6. Epub 2021 Aug 6.

Echo Lab, Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, 238# Jiefang Road, Wuhan, 430060, China.

The probability of toxicity-related myocardial injury event with anthracyclines is controversial, which could be related to the underlying cardiac status before chemotherapy. Our study sought to investigate the influence of cardiovascular risk factors on myocardial motion and cardiac function using layer-specific speckle tracking echocardiography (STE) during chemotherapy with epirubicin. Female patients with first-diagnosed breast cancer were prospectively enrolled in our study and received 4 chemotherapeutic cycles with epirubicin in each cycle of 21 days. All patients underwent echocardiography for layer-specific STE analysis before and after all chemotherapy. Clinical data including cardiovascular risk factors were collected. According to the Framingham score, patients with cardiovascular risk factors were divided into groups with low, medium, and high risk. 134 patients existed in the final analysis. The accumulated dose of epirubicin for were 560.0 ± 103.8 mg. 97 (72.4%) patients had cardiovascular risk factors. According to the Framingham score, 57 (42.5%) patients categorized in high risk. Endocardial layer strain after chemotherapy were lower than those at baseline (p < 0.05, all), especially for patients with high risk. The changes of endocardial longitudinal strain during chemotherapy were associated with cardiovascular risks at baseline with correlation coefficient of 0.627. Our study found that layer-specific STE is valuable for early detection of toxicity-related myocardial injury for patients with breast cancer after epirubicin chemotherapy and cardiovascular risk factors have greatly influenced on cardiac function during chemotherapy. The endocardial layer strain is sensitive to evaluate early-stage toxicity-related myocardial injury after epirubicin chemotherapy.
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http://dx.doi.org/10.1007/s10554-021-02367-0DOI Listing
August 2021

Proanthocyanidins attenuate the high glucose-induced damage of retinal pigment epithelial cells by attenuating oxidative stress and inhibiting activation of the NLRP3 inflammasome.

J Biochem Mol Toxicol 2021 Sep 2;35(9):e22845. Epub 2021 Aug 2.

Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Diabetic retinopathy (DR) is a common diabetic complication known to cause vision impairment and blindness. Previous studies have demonstrated that proanthocyanidins (PACs), polyphenols that are naturally found in several plants and fruits, have powerful antioxidant and anti-inflammatory effects on various cells. However, the effects and underlying mechanism of PACs against DR pathogenesis remain unknown. Here, we investigated the proliferation, apoptosis, and mechanisms of ARPE-19 cells in response to oxidative stress and inflammation under high-glucose conditions with or without PACs treatment. The Cell-Counting Kit-8 assay and western blot analysis showed that treatment with 10 μl PACs significantly increased cell proliferation and the expression level of Bcl-2 in ARPE-19 cells under high-glucose conditions. Moreover, PACs attenuated the high glucose-induced apoptosis, and the increased expression levels of caspase-3 and Bax. Under high-glucose conditions, the generation of reactive oxygen species (ROS) and levels of malondialdehyde increased, whereas the superoxide dismutase content decreased. Moreover, the expression level of the NLRP3 inflammasome, and the release of interleukin 1β (IL-1β) and IL-18 increased. PACs reversed all of these high glucose-induced effects on ARPE-19 cells. Additionally, exposure to nigericin sodium salt, an agonist of the NLRP3 inflammasome, upregulated expression of the NLRP3 inflammasome accompanied by the release of IL-1β and IL-18. Again, treatment with PACs markedly downregulated these effects. Collectively, these results demonstrate that PACs can prevent retinal pigment epithelial cells from high glucose-induced injury via inhibiting the generation of ROS and activation of the NLRP3 inflammasome, suggesting PACs as a potential candidate for the management of DR.
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http://dx.doi.org/10.1002/jbt.22845DOI Listing
September 2021

The Synergistic Effects of Celastrol in combination with Tamoxifen on Apoptosis and Autophagy in MCF-7 Cells.

J Immunol Res 2021 22;2021:5532269. Epub 2021 Jul 22.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, China.

Breast cancer is one of the most common cancers among females and is associated with high mortality and morbidity rates. Several studies have demonstrated that combination treatments with natural products and tamoxifen can improve the sensitivity and cytotoxicity of oestrogen-positive breast cancer cells in response to tamoxifen. Celastrol, a triterpene from traditional Chinese medicine, has been proven to exert significant anticancer effects on various cancers. Our study is aimed at exploring the interactive antitumour effects of celastrol combined with tamoxifen and the potential underlying anticancer mechanisms in MCF-7 cells. The results from MTT assays, isobolographic analyses, and clonogenic cell survival assays revealed that a combination of celastrol and tamoxifen exerted synergistic cytotoxic effects in MCF-7 cells. The results from Annexin V/PI staining and flow cytometry analysis suggested that celastrol enhanced tamoxifen-mediated apoptosis. In addition, exposure to a combination of celastrol and tamoxifen inhibited cell proliferation by causing G1 phase cell cycle arrest. Moreover, the distribution of LC3 was monitored by immunofluorescence, and the changes in the LC3II and P62 levels detected by western blot analysis suggested that celastrol in combination with tamoxifen triggered autophagy. Furthermore, the decrease in p-Akt and p-mTOR in MCF-7 cells, along with the increase in the autophagy marker proteins LC3II and P62, suggested that the Akt/mTOR pathway might be involved in the triggering of cell autophagy by the combination treatment. However, in an MCF-7-implanted nude mouse model, it was possible to detect significantly decreased tumour volumes and tumour weights and decreased p-Akt and p-mTOR protein expression in the celastrol+tamoxifen group. Therefore, our study provides the first evidence that celastrol combined with tamoxifen exerts synergistic anticancer effects by inducing apoptosis and autophagy in MCF-7 cells. Considering the urgent need for novel therapeutic strategies in anticancer therapy, this combinatorial approach is worthy of further investigation.
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http://dx.doi.org/10.1155/2021/5532269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324338PMC
July 2021

Traditional Chinese Medication Qiliqiangxin Attenuates Diabetic Cardiomyopathy via Activating PPARγ.

Front Cardiovasc Med 2021 16;8:698056. Epub 2021 Jul 16.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Diabetic cardiomyopathy is the primary complication associated with diabetes mellitus and also is a major cause of death and disability. Limited pharmacological therapies are available for diabetic cardiomyopathy. Qiliqiangxin (QLQX), a Chinese medication, has been proven to be beneficial for heart failure patients. However, the role and the underlying protective mechanisms of QLQX in diabetic cardiomyopathy remain largely unexplored. Primary neonatal rat cardiomyocytes (NRCMs) were treated with glucose (HG, 40 mM) to establish the hyperglycemia-induced apoptosis model . Streptozotocin (STZ, 50 mg/kg/day for 5 consecutive days) was intraperitoneally injected into mice to establish the diabetic cardiomyopathy model . Various analyses including qRT-PCR, western blot, immunofluorescence [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining] histology (hematoxylin-eosin and Masson's trichrome staining), and cardiac function (echocardiography) were performed in these mice. QLQX (0.5 μg/ml and 0.5 g/kg/day ) was used in this study. QLQX attenuated hyperglycemia-induced cardiomyocyte apoptosis via activating peroxisome proliferation-activated receptor γ (PPARγ). , QLQX treatment protected mice against STZ-induced cardiac dysfunction and pathological remodeling. QLQX attenuates diabetic cardiomyopathy via activating PPARγ.
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http://dx.doi.org/10.3389/fcvm.2021.698056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322738PMC
July 2021

LINC00261 Suppresses Cisplatin Resistance of Esophageal Squamous Cell Carcinoma Through miR-545-3p/MT1M Axis.

Front Cell Dev Biol 2021 15;9:687788. Epub 2021 Jul 15.

Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

To improve the survival rate and cure rate of patients, it is necessary to find a new treatment scheme according to the molecular composition of (ESCC) in esophageal squamous cell carcinoma. Long non-coding RNAs (lncRNAs) regulate the progression of ESCC by various pathophysiological pathways. We explored the possible function of the lncRNA LINC00261 (LINC00261) on cisplatin (DDP) resistance of ESCC and its relative molecular mechanisms. In the study, we found that LINC00261 was downregulated in ESCC tissues, cell lines, and DDP-resistant ESCC patients. Besides, overexpression of LINC00261 not only inhibited cell proliferation, and DDP resistance but also promotes cell apoptosis. Further mechanistic research showed that LINC00261 sponged miR-545-3p which was negatively correlated with the expression of LINC00261. In addition, functional experiments revealed that upregulation of miR-766-5p promoted proliferation and enhanced DDP resistance. Subsequently, MT1M was testified to be the downstream target gene of miR-545-3p. Rescue experiments revealed that overexpression of MT1M largely restores miR-545-3p mimics-mediated function on ESCC progression. Our results demonstrate that the LINC00261 suppressed the DDP resistance of ESCC through miR-545-3p/MT1M axis.
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http://dx.doi.org/10.3389/fcell.2021.687788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320661PMC
July 2021

The Co-occurrence of Chronic Hepatitis B and Fibrosis Is Associated With a Decrease in Hepatic Global DNA Methylation Levels in Patients With Non-alcoholic Fatty Liver Disease.

Front Genet 2021 14;12:671552. Epub 2021 Jul 14.

Department of Nutrition, School of Medicine, Jinan University, Guangzhou, China.

Global DNA hypomethylation has been reported in patients with chronic hepatitis B (CHB) and non-alcoholic fatty-liver disease (NAFLD). However, the global DNA methylation profile of patients with concurrent NAFLD and CHB (NAFLD + CHB) is still unclear. We aimed to detect the hepatic global DNA methylation levels of NAFLD + CHB patients and assess the associated risk factors. Liver biopsies were collected from 55 NAFLD patients with or without CHB. The histological characteristics of the biopsy were then assessed. Hepatic global DNA methylation levels were quantified by fluorometric method. The hepatic global DNA methylation levels in NAFLD + CHB group were significantly lower than that in NAFLD group. Participants with fibrosis showed lower levels of hepatic global DNA methylation than those without fibrosis. Participants with both CHB and fibrosis had lower levels of hepatic global DNA methylation than those without either CHB or fibrosis. The co-occurrence of CHB and fibrosis was significantly associated with a reduction in global DNA methylation levels compared to the absence of both CHB and fibrosis. Our study suggests that patients with NAFLD + CHB exhibited lower levels of global DNA methylation than patients who had NAFLD alone. The co-occurrence of CHB and liver fibrosis in NAFLD patients was associated with a decrease in global DNA methylation levels.
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http://dx.doi.org/10.3389/fgene.2021.671552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318039PMC
July 2021

A bioinspired cercosporin/polymethylmethacrylate photocatalyst with high efficiency for decontamination of pharmaceuticals and pathogens.

J Hazard Mater 2021 Oct 1;419:126555. Epub 2021 Jul 1.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China. Electronic address:

Pharmaceuticals have seriously contaminated aquatic environments and resulted in the formation of drug-tolerant bacteria owing to continuous release and accumulation. Therefore, the development of new methods to simultaneously decompose drugs and disinfect pathogens in an environmental-friendly manner with high efficiency is still in great demand. Bioinspired by the great photosensitivity of natural product cercosporin with the ability to efficiently generate reactive oxygen species (ROS) under natural sunlight and its antibacterial activity, here a novel cercosporin/polymethylmethacrylate (CP/PMMA) photocatalyst was rationally developed by incorporating and restricting cercosporin in a "green" macroporous resin PMMA, which greatly improved the ROS generation efficiency and displayed 97.2-100% photodegradation for broad-spectrum pharmaceuticals, including fluoroquinolones, trimethoprim and chloroquine phosphate, upon 15 W compact fluorescent lamp irradiation. More importantly, this decontamination efficiency was greatly improved, and the decontamination time was substantially shortened in a large-scale assay under natural sunlight. Furthermore, it could inactivate the pathogen Staphylococcus aureus. Overall, this work provides new insight into how a multifunctional photocatalyst could be designed using a natural product and macroporous resins for environmental remediation.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126555DOI Listing
October 2021

Correction: H3K36 methyltransferase NSD1 regulates chondrocyte differentiation for skeletal development and fracture repair.

Bone Res 2021 Jul 26;9(1):34. Epub 2021 Jul 26.

Shanghai Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

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http://dx.doi.org/10.1038/s41413-021-00160-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313643PMC
July 2021

Etomidate ameliorated advanced glycation end-products (AGEs)-induced reduction of extracellular matrix genes expression in chondrocytes.

Bioengineered 2021 12;12(1):4191-4200

Department of Anus& Intestine Surgery, Tianjin Hospital, Tianjin, China.

Osteoarthritis (OA) is a rheumatic disease common in the elderly. AGEs are the end products of glycation reactions and play an important role in the development of OA. Etomidate is a general anesthesia-inducing agent recently reported to exert significant anti-inflammatory effects. The present study aims to explore the protective effect of Etomidate against advanced glycation end-products (AGEs)-induced reduction of extracellular matrix gene expression in chondrocytes. In the present study, we found that AGEs significantly reduced the expression of Collagen II () and Aggrecan () at the gene level. Furthermore, AGEs inhibited the expression of SRY-related high mobility group-box gene 9 (SOX-9), promoting the expression of COL2A1 and ACAN. , and in chondrocytes were significantly elevated by treatment with Etomidate alone. Consistently, Etomidate ameliorated AGEs-induced downregulation of , and SOX-9 in a dose-dependent manner. Importantly, we found that knockdown of SOX-9 eliminated the beneficial effects of Etomidate against AGEs-induced decrease in . Based on these findings, we demonstrated that Etomidate could ameliorate AGEs-induced reduction of extracellular matrix gene expression in chondrocytes by upregulating SOX-9.
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http://dx.doi.org/10.1080/21655979.2021.1951926DOI Listing
December 2021

ADAR2 increases in exercised heart and protects against myocardial infarction and doxorubicin-induced cardiotoxicity.

Mol Ther 2021 Jul 16. Epub 2021 Jul 16.

Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai 200444, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China. Electronic address:

Exercise training benefits the heart. The knowledge of post-transcription regulation, especially RNA editing, in hearts remain rare. ADAR2 is an enzyme that edits adenosine to inosine nucleotides in double-stranded RNA, and RNA editing is associated with many human diseases. We found that ADAR2 was upregulated in hearts during exercise training. AAV9-mediated cardiac-specific ADAR2 overexpression attenuated acute myocardial infarction (AMI), MI remodeling, and doxorubicin (DOX)-induced cardiotoxicity. In vitro, overexpression of ADAR2 inhibited DOX-induced cardiomyocyte (CM) apoptosis. but it could also induce neonatal rat CM proliferation. Mechanistically, ADAR2 could regulate the abundance of mature miR-34a in CMs. Regulations of miR-34a or its target genes (Sirt1, Cyclin D1, and Bcl2) could affect the pro-proliferation and anti-apoptosis effects of ADAR2 on CMs. These data demonstrated that exercise-induced ADAR2 protects the heart from MI and DOX-induced cardiotoxicity. Our work suggests that ADAR2 overexpression or a post-transcriptional associated RNA editing via ADAR2 may be a promising therapeutic strategy for heart diseases.
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http://dx.doi.org/10.1016/j.ymthe.2021.07.004DOI Listing
July 2021

RNA-seq between asexual archeospores and meiosis-related conchospores in Neopyropia yezoensis using Smart-seq2.

J Phycol 2021 Jul 14. Epub 2021 Jul 14.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

In the life cycle of Neopyropia yezoensis, a potential model system for marine macroalgae, both asexual archeospores and meiosis-related conchospores develop into thalli (gametophyte). To understand this special life phenomenon in macroalgae, we picked out the two kinds of spores (10-30 cells in each sample) and conducted RNA-seq using Smart-seq2. Comparative analysis showed that light capture and carbon fixation associated differentially expressed genes (DEGs) were upregulated in archeospores, thus indicating that archeospores are in a state of rapid vegetative growth. In conchospores, protein synthesis and degradation, especially molecular chaperone, associated DEGs were up-regulated, indicating that complex life activities might be occurring in conchospores. There were 68 genes related to DNA replication and repair expressed in conchospores, showing that active DNA replication might occur in conchospores. Moreover, we found that one conchospore specifically expressed DEG (py04595: DNA helicase) only in diploid stages (conchocelis, sporangial filament) and three archeospores specifically expressed DEGs only in haploid stages (thalli). These molecular level results indicated that conchospores were closer to diploid, and might be the meiotic mother cells of N. yezoensis. In addition, we found that the knotted-like homeobox gene (PyKNOX), which might relate to the transition of gametophyte from sporophyte, was only expressed in sporophyte generation but not expressed in conchospores, archeospores and thalli, indicating the morphogenesis of gametophyte sin N. yezoensis might require the inactivation of PyKNOX.
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http://dx.doi.org/10.1111/jpy.13197DOI Listing
July 2021

Characterization of Respiratory Symptoms Among Youth Using Heated Tobacco Products in Hong Kong.

JAMA Netw Open 2021 Jul 1;4(7):e2117055. Epub 2021 Jul 1.

School of Nursing, University of Hong Kong, Hong Kong, China.

Importance: Heated tobacco products (HTPs) are promoted as less harmful than combustible cigarettes but epidemiological evidence is scarce, especially in youth.

Objective: To investigate the associations of persistent respiratory symptoms with HTP use, cigarette use, and dual use among Hong Kong youth.

Design, Setting, And Participants: This was a territorywide cross-sectional school-based survey conducted from October 2018 to July 2019 using an anonymous questionnaire. Schools were randomly invited from a proportionate stratified sample in all 18 districts of Hong Kong. Poisson regression models using generalized estimating equations yielded adjusted prevalence ratios (APRs) of respiratory symptoms in (1) former and current HTP (vs never) users in the whole sample and stratified by cigarette use status and (2) exclusive HTP and dual users vs exclusive cigarette users. Statistical analysis was performed from October 2020 to March 2021.

Exposures: Former and current use of cigarettes, HTPs, e-cigarettes, and other tobacco products.

Main Outcomes And Measures: Respiratory symptoms for 3 consecutive months in the past 12 months.

Results: The study included 33 627 students with a mean (SD) age of 14.8 (1.9) years; 51.3% (18 171) were boys. Respiratory symptoms were reported by 16.3% (n = 5549) of all students, 29.3% (n = 226) of current users of e-cigarettes, 31.2% (n = 314) of current users of cigarettes, and 33.5% (n = 179) of current users of HTPs. Respiratory symptoms were associated with former (APR, 1.30; 95% CI, 1.06-1.59) and current (APR, 1.59; 95% CI, 1.23-2.06) vs never HTP use and current vs never cigarette use (APR, 1.50; 95% CI, 1.30-1.74) after adjusting for various tobacco use. Associations between respiratory symptoms and current vs never HTP use were observed in never (APR, 1.88; 95% CI, 1.36-2.59) and former (APR, 2.15; 95% CI, 1.12-4.12) cigarette users, but not in current cigarette users (APR, 1.24; 95% CI, 0.97-1.59). Respiratory symptoms were associated with exclusive ever HTP use (APR, 1.46, 95% CI, 1.15-1.86) and ever dual use (APR, 1.29; 95% CI, 1.08-1.54) vs exclusive ever cigarette use. There was no association between exclusive current HTP (vs cigarette) use and respiratory symptoms (1.40; 95% CI, 0.93-2.11).

Conclusions And Relevance: This cross-sectional study found that former and current HTP use were associated with persistent respiratory symptoms among youth, especially among never and former cigarette users. Respiratory symptoms were more prevalent in ever exclusive HTP users and ever dual users than ever exclusive cigarette users. These findings suggest that using HTPs instead of cigarettes may not reduce health risks.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.17055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280960PMC
July 2021

First Chinese patient with mental retardation-40 due to a CHAMP1 frameshift mutation: Case report and literature review.

Exp Ther Med 2021 Aug 25;22(2):907. Epub 2021 Jun 25.

Neurology Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.

Mental retardation-40 (MRD40) is a rare autosomal dominant neurodevelopmental disorder with a poor prognosis that is caused by a heterozygous mutation in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). It was previously considered a non-syndromic disease due to the lack of specific external features. Only limited international reports describing CHAMP1 mutations are currently available. The present case study was the first to report on a Chinese patient with MRD40. The patient presented with severe global development delay with significant craniofacial dysmorphia. Using trio whole-exome sequencing, a novel frameshift mutation in CHAMP1, NM_032436.2: c.530delCinsTTT, was identified, which expands the spectrum of the known pathogenic variants. The present case report helps to improve the syndromic profile of the rare MRD40 disorder and provides an example for the clinical diagnosis of MRD40.
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http://dx.doi.org/10.3892/etm.2021.10339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243316PMC
August 2021

Improvement of the ultra-low-frequency active vertical vibration isolator with geometric anti-spring structure for absolute gravimetry.

Rev Sci Instrum 2021 May;92(5):054503

State Key Laboratory of Precision Measurement Technology and Instruments, Tsinghua University, Beijing 100084, China.

For absolute gravimeters, which play important roles in geophysics and geological exploration, an ultra-low-frequency vertical vibration isolator is necessary to achieve the required measurement precision. A novel active vibration isolator that uses a geometric anti-spring (GAS) structure has been proposed by our team at Tsinghua University previously, but its performance is mainly limited by the large-scale drift in the detection signal of the system. In this paper, after a brief theoretical introduction to the overall system, recent improvements in this novel vibration isolator are presented. The main improvements to the isolator are the use of new blades in the GAS structure and the addition of an extra compensation circuit to eliminate the drift. The improved prototype has a resonance period of 29.2 s and a continuous working time of several days, as compared with the resonance period of 19.2 s and a working time lasting only several minutes of the previous prototype. Experiments show that the improved prototype performs well in the homemade T-1 laser-interferometry absolute gravimeter. The standard error of the mean (SEM) of a 50-drop measurement performed in Tsinghua University is reduced significantly from 404 μGal (1 μGal = 1 × 10 m s) without the vibration isolator to 10.8 μGal with the improved prototype at its best level. Additionally, the SEM of a 50-set measurement (including 800 drops) lasting for 25 h achieves 5.9 μGal with the improved prototype.
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http://dx.doi.org/10.1063/5.0049925DOI Listing
May 2021

Enhanced Prodigiosin Production in JNB5-1 by Introduction of a Polynucleotide Fragment into the 3' Untranslated Region and Disulfide Bonds into -Methyl Transferase (PigF).

Appl Environ Microbiol 2021 08 26;87(18):e0054321. Epub 2021 Aug 26.

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan Universitygrid.258151.a, Wuxi, Jiangsu, China.

In Serratia marcescens JNB5-1, prodigiosin was highly produced at 30°C, but it was noticeably repressed at ≥37°C. Our initial results demonstrated that both the production and the stability of the -methyl transferase (PigF) and oxidoreductase (PigN) involved in the prodigiosin pathway in S. marcescens JNB5-1 sharply decreased at ≥37°C. Therefore, in this study, we improved mRNA stability and protein production using polynucleotide fragments (PNFs) and the introduction of disulfide bonds, respectively, and observed their effects on prodigiosin production. Our results demonstrate that adding PNFs at the 3' untranslated regions of and significantly improved the mRNA half-lives of these genes, leading to an increase in the transcript and expression levels. Subsequently, the introduction of disulfide bonds in improved the thermal stability, pH stability, and copper ion resistance of PigF. Finally, shake flask fermentation showed that the prodigiosin titer with the engineered S. marcescens was increased by 61.38% from 5.36 to 8.65 g/liter compared to the JNB5-1 strain at 30°C and, significantly, the prodigiosin yield increased 2.05-fold from 0.38 to 0.78 g/liter at 37°C. In this study, we revealed that the introduction of PNFs and disulfide bonds greatly improved the expression and stability of and , hence efficiently enhancing prodigiosin production with S. marcescens at 30 and 37°C. This study highlights a promising strategy to improve mRNA/enzyme stability and to increase production using PNF libraries and the introduction of disulfide bonds into the protein. PNFs could increase the half-life of target gene mRNA and effectively prevent its degradation. Moreover, PNFs could increase the relative intensity of target genes without affecting the expression of other genes; as a result, it could alleviate the cellular burden compared to other regulatory elements such as promoters. In addition, we obtained a PigF variant with improved activity and stability by the introduction of disulfide bonds into PigF. Collectively, we demonstrate here a novel approach for improving mRNA/enzyme stability using PNFs, which results in enhanced prodigiosin production in S. marcescens at 30°C.
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http://dx.doi.org/10.1128/AEM.00543-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388806PMC
August 2021

Smart Nanoparticles for Chemo-Based Combinational Therapy.

Pharmaceutics 2021 Jun 8;13(6). Epub 2021 Jun 8.

Department of Biomedical and Chemical Engineering, The University of Texas at San Antonio, San Antonio, TX 78249, USA.

Cancer is a heterogeneous and complex disease. Traditional cancer therapy is associated with low therapeutic index, acquired resistance, and various adverse effects. With the increasing understanding of cancer biology and technology advancements, more strategies have been exploited to optimize the therapeutic outcomes. The rapid development and application of nanomedicine have motivated this progress. Combinational regimen, for instance, has become an indispensable approach for effective cancer treatment, including the combination of chemotherapeutic agents, chemo-energy, chemo-gene, chemo-small molecules, and chemo-immunology. Additionally, smart nanoplatforms that respond to external stimuli (such as light, temperature, ultrasound, and magnetic field), and/or to internal stimuli (such as changes in pH, enzymes, hypoxia, and redox) have been extensively investigated to improve precision therapy. Smart nanoplatforms for combinational therapy have demonstrated the potential to be the next generation cancer treatment regimen. This review aims to highlight the recent advances in smart combinational therapy.
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http://dx.doi.org/10.3390/pharmaceutics13060853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227511PMC
June 2021
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