Publications by authors named "Ping Wang"

4,684 Publications

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Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown.

Front Pediatr 2021 12;9:647880. Epub 2021 Jul 12.

Neonatal Intensive Care Unit, Department of Pediatrics, University of Liege, Liege, Belgium.

To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (-6.6%, 95% CI -18.2 to +7.1%, = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions ( = 7,499 in 2020 vs. = 8,362 in 2019). This study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601.
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http://dx.doi.org/10.3389/fped.2021.647880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310995PMC
July 2021

Global identification and characterization of tRNA-derived RNA fragment landscapes across human cancers.

NAR Cancer 2020 Dec 19;2(4):zcaa031. Epub 2020 Oct 19.

Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Department of Gynecologic Oncology, Women's Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.

Transfer RNA-derived RNA fragments (tRFs) are a class of small non-coding RNAs that are abundant in many organisms, but their role in cancer has not been fully explored. Here, we report a functional genomic landscape of tRFs in 8118 specimens across 15 cancer types from The Cancer Genome Atlas. These tRFs exhibited characteristics of widespread expression, high sequence conservation, cytoplasmic localization, specific patterns of tRNA cleavage and conserved cleavage in tissues. A cross-tumor analysis revealed significant commonality among tRF expression subtypes from distinct tissues of origins, characterized by upregulation of a group of tRFs with similar size and activation of cancer-associated signaling. One of the largest superclusters was composed of 22 nt 3'-tRFs upregulated in 13 cancer types, all of which share the activation of Ras/MAPK, RTK and TSC/mTOR signaling. tRF-based subgrouping provided clinically relevant stratifications and significantly improved outcome prediction by incorporating clinical variables. Additionally, we discovered 11 cancer driver tRFs using an effective approach for accurately exploring cross-tumor and platform trends. As a proof of concept, we performed comprehensive functional assays on a non-microRNA driver tRF, 5'-IleAAT-8-1-L20, and validated its oncogenic roles in lung cancer and . Our study also provides a valuable tRF resource for identifying diagnostic and prognostic biomarkers, developing cancer therapy and studying cancer pathogenesis.
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http://dx.doi.org/10.1093/narcan/zcaa031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210304PMC
December 2020

Hospitalization Risk for Medicare Beneficiaries With Nontuberculous Mycobacterial Pulmonary Disease.

Chest 2021 Jul 24. Epub 2021 Jul 24.

Medical University of South Carolina, Charleston, SC, US.

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an uncommon mycobacterial infection characterized by worsening lung function and increased healthcare resource utilization; however, overall risk for hospitalization among patients with NTM-PD remains unclear.

Study Design And Methods: A retrospective, nested, case-control study was conducted using the Medicare claims database. Cases were defined as patients with ≥2 NTM-PD claims ≥30 days apart between 1/1/07 and 12/31/15. We included individuals aged ≥65 years with ≥12 months of continuous enrollment in both Parts A and B before the first NTM-PD diagnosis. Cases were matched 1:2 to Medicare beneficiaries without NTM-PD (controls) by age and sex. Hospitalizations following the first NTM-PD claim were compared between cases and controls using both univariate and multivariate analysis.

Results: We identified 35,444 cases and 65,467 matched controls (mean age, 76.6 years; 70% female; ≥87% White). Baseline comorbidities, particularly pulmonary comorbidities, were more common in cases than controls (81.1% vs 17.7% for chronic obstructive pulmonary disease; 44.6% vs 0.6% for bronchiectasis). All-cause hospitalization was observed in 65.7% of cases and 44.9% of controls. Unadjusted annual hospitalization rates were significantly (P<0.05) greater among cases than controls. Cases also had a significantly shorter time to hospitalization than controls. The increased burden due to hospitalization was reflected in multivariate analysis adjusting for baseline comorbidities. All-cause hospitalization in patients with NTM-PD relative to controls was 1.2-times more likely (relative risk, 1.23; 95% CI, 1.21-1.25; P<0.0001) with a 46% greater hazard (hazard ratio, 1.46; 95% CI, 1.43-1.50; P<0.0001).

Interpretation: Patients with NTM-PD were significantly more likely to be hospitalized, had greater annualized hospitalization rates, and had shorter time to hospitalization than age- and sex-matched controls without NTM-PD. These findings highlight the significantly increased burden of hospitalizations among patients with NTM-PD.
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http://dx.doi.org/10.1016/j.chest.2021.07.034DOI Listing
July 2021

Geographic, gender and seasonal variation of diabetes: a nationwide study among 1.4 million participants.

J Clin Endocrinol Metab 2021 Jul 27. Epub 2021 Jul 27.

School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.

Background: China experienced a rapid increase in the prevalence of diabetes.

Objectives: To assess the prevalence of diabetes among Chinese adults who attend preventive physical examination, and analyzed geographical and gender difference in seasonal variation of fasting blood glucose (FBG).

Methods: The study used data from 1,390,088 participants attending preventive health examination at 430 health screening centers in 220 cities. Diagnosis of diabetes and prediabetes were based on FBG and hemoglobinA1c and self-report physician's diagnosis. We calculated age and sex standardized prevalence of diabetes according to the sixth Chinese population census data in 2010. Geographical distribution of diabetes and prediabetes were displayed on the country map. FBG were analyzed to detect the seasonal variation adjusted for age and gender by geographic location.

Results: The standardized prevalence of diabetes was 8.70% (95% CI, 8.22%-9.19%), 10.7% in men and 6.61% in women. Among those with diabetes, 43.7% (95% CI, 40.9%-46.5%) were aware of their conditions and 38.5% (95% CI, 36.0%-41.1%) were treated. Only 49.3% (95% CI, 47.0%-51.6%) of treated patients achieved glycemic control. The mean level of FBG was higher in winter than summer and in the northern than the southern.

Conclusions: The prevalence of diabetes was high whilst the percentages of awareness, treatment and glycemic control were low among adults. Effective measures are needed to prevent and manage diabetes in China. Geographic and seasonal variation of diabetes should be considered for its prevention and control.
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http://dx.doi.org/10.1210/clinem/dgab543DOI Listing
July 2021

Anterograde regulation of mitochondrial genes and FGF21 signaling by hepatic LSD1.

JCI Insight 2021 Jul 27. Epub 2021 Jul 27.

Department of Medicine, Physiology and Biophysics, University of California, Irvine, Irvine, United States of America.

Mitochondrial biogenesis and function are controlled by anterograde regulatory pathways involving more than one thousand nuclear-encoded proteins. Transcriptional networks controlling the nuclear-encoded mitochondrial genes remain to be fully elucidated. Here we show that histone demethylase LSD1 knockout from adult mouse liver (LSD1-LKO) reduces the expression of one-third of all nuclear-encoded mitochondrial genes and decreases mitochondrial biogenesis and function. LSD1-modulated histone methylation epigenetically regulates nuclear-encoded mitochondrial genes. Furthermore, LSD1 regulates gene expression and protein methylation of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), which controls the final step of NAD+ synthesis and limits NAD+ availability in nucleus. Lsd1 knockout reduces NAD+-dependent SIRT1 and SIRT7 deacetylase activity, leading to hyperacetylation and hypofunctioning of GABPβ and PGC-1α, the major transcriptional factor/cofactor for nuclear-encoded mitochondrial genes. Despite the reduced mitochondrial function in liver, LSD1-LKO mice are protected from diet-induced hepatic steatosis and glucose intolerance, partially due to induction of hepatokine FGF21. Thus, LSD1 orchestrates a core regulatory network involving epigenetic modifications and NAD+ synthesis to control mitochondrial function and hepatokine production.
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http://dx.doi.org/10.1172/jci.insight.147692DOI Listing
July 2021

Risk factors related to postoperative recurrence of dermatofibrosarcoma protuberans: A retrospective study and literature review.

World J Clin Cases 2021 Jul;9(20):5442-5452

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade malignant soft tissue tumor characterized by rosette-like infiltrative growth. Postoperative recurrence of this tumor is very common.

Aim: To evaluate the risk factors related to recurrence after wide local excision (WLE) of DFSP and to guide clinical diagnosis and treatment.

Methods: The medical records of 44 DFSP patients confirmed by pathology at our hospital from 2012 to 2019 were retrospectively reviewed. The relationship between clinical features, tumor characteristics, treatment, and recurrence risk were analyzed, and the possible risk factors for postoperative tumor recurrence were evaluated.

Results: There were 44 patients in total, including 21 males and 23 females. The median progression free survival was 36 mo (range, 1-240 mo). Twenty patients were treated for the first time, while 24 had previous treatment experience. Forty-two cases were followed for 25.76 ± 22.0 mo, among whom four (9.52%) experienced recurrence after WLE (rate was 9.52%). The recurrence rate in the recurrent group was higher than that in the patients with primary tumor (19.05% 0%, = 0.028). Eighteen cases had a history of misdiagnosis (rate was 40.91%). The recurrence rate among patients with previous experience of misdiagnosis was significantly higher than in patients without (68% 36.84%, = 0.04). The tumor diameter in patients with a history of treatment was larger than in patients treated for the first time (4.75 ± 0.70 cm 2.25 ± 0.36 cm, = 0.004).

Conclusion: To sum up, the clinical manifestations of DFSP are not specific and are easily misdiagnosed, thus commonly causing the recurrence of DFSP. After incomplete resection, the tumor may rapidly grow. Previous recurrence history may be a risk factor for postoperative recurrence, and tumor location may have an indirect effect on postoperative recurrence; however, we found no significant correlation between sex, age, course of the disease, or tumor size and postoperative recurrence.
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http://dx.doi.org/10.12998/wjcc.v9.i20.5442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281415PMC
July 2021

Long non-coding RNA B3GALT5-AS1 contributes to the progression of gastric cancer via interacting with CSNK2A1.

Exp Ther Med 2021 Sep 30;22(3):927. Epub 2021 Jun 30.

Center of Digestive Endoscopy, Tianjin Fifth Central Hospital, Tianjin 300451, P.R. China.

Gastric cancer is a type of cancer that is characterized by high morbidity and mortality rates. Long non-coding RNA (lncRNA) β-1,3-galactosyltransferase 5-AS1 (B3GALT5-AS1) was previously found to be highly expressed in the serum of patients with gastric cancer. However, the regulatory effects of B3GALT5-AS1 in gastric cancer remain poorly understood. The present study aimed to investigate the effects of B3GALT5-AS1 in gastric cancer cell lines. The expression levels of B3GALT5-AS1 were determined in different gastric cancer cell lines (AGS, HGC-27 and MKN-45) using reverse transcription-quantitative PCR. The potential interaction between B3GALT5-AS1 and casein kinase 2 a1 (CSNK2A1) was evaluated using an RNA binding protein immunoprecipitation and RNA pull down assays. Western blot analysis was performed to measure protein expression levels. Cell Counting Kit-8 assay was utilized to determine cell viability, whilst cell invasion and migration were assessed using Transwell and wound healing assays, respectively. Apoptotic cells were evaluated using TUNEL assays. The results showed that B3GALT5-AS1 expression was upregulated in MKN-45 cells compared with the control group. In addition, B3GALT5-AS1 could bind to CSNK2A1 to regulate its expression. B3GALT5-AS1 knockdown attenuated cell viability, invasion and migration, whilst promoting cell apoptosis. These effects were partly reversed by CSNK2A1 overexpression. Overall, results of the present study revealed that interference with B3GALT5-AS1 impeded gastric cancer cell migration and invasion whilst promoting apoptosis by regulating CSNK2A1 expression. These findings suggested that B3GALT5-AS1 and CSNK2A1 may serve a tumorigenic role in the progression of gastric cancer and serve as therapeutic targets for this type of cancer.
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http://dx.doi.org/10.3892/etm.2021.10359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281446PMC
September 2021

Silencing of long non-coding RNA KCNQ1OT1 alleviates LPS-induced lung injury by regulating the miR-370-3p/FOXM1 axis in childhood pneumonia.

BMC Pulm Med 2021 Jul 23;21(1):247. Epub 2021 Jul 23.

Department of Pediatrics I, Qingdao Hospital of Traditional Chinese Medicine (Qingdao Hiser Hospital), No. 4, Renmin Road, Shibei District, Qingdao City, 266033, Shandong Province, China.

Purpose: Long non-coding RNAs (lncRNAs) play important roles in the development of pneumonia. We aimed to explore the role of the lncRNA KCNQ1OT1 in pneumonia and its underlying mechanisms.

Methods: The expression of KCNQ1OT1, FOXM1, and miR-370-3p was detected in the serum of 24 children with pneumonia and in 24 healthy controls. Normal human embryonic lung-derived diploid fibroblasts (WI-38 cells) were stimulated with LPS (10 μg/mL) to simulate the cellular model of pneumonia, and cell viability, apoptosis, and inflammation were analysed. Dual luciferase reporter and/or RNA binding protein immunoprecipitation assays were performed to test the relationship between miR-370-3p and KCNQ1OT1/FOXM1. Mice were intratracheally administered LPS (5 mg/kg) to induce an in vivo model of pneumonia, and pathological injury and inflammation were analysed.

Results: The expression of KCNQ1OT1 and FOXM1 was up-regulated, and miR-370-3p was down-regulated in the serum of children with pneumonia, LPS-treated WI-38 cells, and in lung tissues of LPS-treated mice. Silencing of KCNQ1OT1 or overexpression of miR-370-3p suppressed cell apoptosis and inflammation and facilitated cell viability in LPS-treated WI-38 cells. KCNQ1OT1 directly targets miR-370-3p and negatively regulates its expression. FOXM1 was targeted by miR-370-3p and negatively modulated by miR-370-3p. In addition, silencing of KCNQ1OT1 mitigated LPS-induced lung injury and inflammation in mice. The protective effects of KCNQ1OT1 silencing in LPS-treated WI-38 cells and mice were reversed by silencing of miR-370-3p or overexpression of FOXM1.

Conclusion: Silencing of KCNQ1OT1 alleviates LPS-induced lung injury by regulating the miR-370-3p/FOXM1 axis in pneumonia.
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http://dx.doi.org/10.1186/s12890-021-01609-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299180PMC
July 2021

Effects of Exercise Training on Cardiopulmonary Function and Quality of Life in Elderly Patients with Pulmonary Fibrosis: A Meta-Analysis.

Int J Environ Res Public Health 2021 Jul 18;18(14). Epub 2021 Jul 18.

Faculty of Sport Science, Research Academy of Grand Health, Ningbo University, Ningbo 315211, China.

(1) Objective: Our objective was to conduct a meta-analysis of randomized controlled trials that have evaluated the benefits of exercise training for elderly pulmonary fibrosis (PF) patients. (2) Methods: Studies in either English or Chinese were retrieved from the China National Knowledge Infrastructure (CNKI) and the Wanfang, PubMed, Web of Science and SPORTDiscus databases from inception until the first week of April 2021. Age, body mass index (BMI), and exercise frequency, intensity, type, and duration were considered for each participant. The specific data recorded were the six-minute walk distance (6MWD), maximal rate of oxygen consumption (peak VO), predicted forced vital capacity (FVC% pred), predicted diffusing capacity of the lung for carbon monoxide (DLCO% pred), predicted total lung capacity (TLC% pred), St. George's respiratory questionnaire (SGRQ) total score and a modified medical research council score (mMRC). (3) Results: Thirteen studies comprised this meta-analysis (eleven randomized controlled trials and two prospective studies design), wherein 335 patients were exercised and 334 were controls. The results showed that exercise training increased the 6MWD (Cohen's = 0.77, MD = 34.04 (95% CI, 26.50-41.58), < 0.01), peak VO (Cohen's = 0.45, MD = 1.13 (95% CI, 0.45-1.82), = 0.0001) and FVC% pred (Cohen's = 0.42, MD = 3.94 (95% CI, 0.91-6.96), = 0.01). However, exercise training reduced scores for the SGRQ (Cohen's = 0.89, MD = -8.79 (95% CI, -10.37 to -7.21), < 0.01) and the mMRC (Cohen's = 0.64, MD = -0.58 (95% CI, -0.79 to -0.36), < 0.01). In contrast, exercise training could not increase DLCO% pred (Cohen's = 0.16, MD = 1.86 (95% CI, -0.37-4.09), = 0.10) and TLC% pred (Cohen's = 0.02, MD = 0.07 (95% CI, -6.53-6.67), = 0.98). Subgroup analysis showed significant differences in frequency, intensity, type, and age in the 6MWD results ( < 0.05), which were higher with low frequency, moderate intensity, aerobic-resistance-flexibility-breathing exercises and age ≤ 70. Meanwhile, the subgroup analysis showed significant differences in exercise intensity and types in the mMRC results ( < 0.05), which were lower with moderate intensity and aerobic-resistance exercises. (4) Conclusions: Exercise training during pulmonary rehabilitation can improved cardiopulmonary endurance and quality of life in elderly patients with PF. The 6MWDs were more noticeable with moderate exercise intensity, combined aerobic-resistance-flexibility-breathing exercises and in younger patients, which all were not affected by BMI levels or exercise durations. As to pulmonary function, exercise training can improve FVC% pred, but has no effect on DLCO% pred and TLC% pred.
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http://dx.doi.org/10.3390/ijerph18147643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306771PMC
July 2021

Extracellular CIRP activates STING to exacerbate hemorrhagic shock.

JCI Insight 2021 Jul 22;6(14). Epub 2021 Jul 22.

Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.

Stimulator of IFN genes (STING) activates TANK-binding kinase 1 (TBK1) and IFN regulatory factor 3 (IRF3) to produce type I IFNs. Extracellular cold-inducible RNA-binding protein (eCIRP) is released from cells during hemorrhagic shock (HS). We hypothesized that eCIRP activates STING to induce inflammation and acute lung injury (ALI) after HS. WT and STING-/- mice underwent controlled hemorrhage by bleeding, followed by fluid resuscitation. Blood and lungs were collected at 4 hours after resuscitation. Serum ALT, AST, LDH, IL-6, and IFN-β were significantly decreased in STING-/- mice compared with WT mice after HS. In STING-/- mice, the levels of pTBK1 and pIRF3, and expression of TNF-α, IL-6, and IL-1β mRNAs and proteins in the lungs, were significantly decreased compared with WT HS mice. The 10-day mortality rate in STING-/- mice was significantly reduced. I.v. injection of recombinant mouse CIRP (rmCIRP) in STING-/- mice showed a significant decrease in pTBK1 and pIRF3 and in IFN-α and IFN-β mRNAs and proteins in the lungs compared with rmCIRP-treated WT mice. Treatment of TLR4-/-, MyD88-/-, and TRIF-/- macrophages with rmCIRP significantly decreased pTBK1 and pIRF3 levels and IFN-α and IFN-β mRNAs and proteins compared with WT macrophages. HS increases eCIRP levels, which activate STING through TLR4/MyD88/TRIF pathways to exacerbate inflammation.
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http://dx.doi.org/10.1172/jci.insight.143715DOI Listing
July 2021

Current Status of Mining, Modification, and Application of Cellulases in Bioactive Substance Extraction.

Curr Issues Mol Biol 2021 Jul 13;43(2):687-703. Epub 2021 Jul 13.

Department of Biochemical Engineering, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300350, China.

Cellulases have been used to extract bioactive ingredients from medical plants; however, the poor enzymatic properties of current cellulases significantly limit their application. Two strategies are expected to address this concern: (1) new cellulase gene mining strategies have been promoted, optimized, and integrated, thanks to the improvement of gene sequencing, genomic data, and algorithm optimization, and (2) known cellulases are being modified, thanks to the development of protein engineering, crystal structure data, and computing power. Here, we focus on mining strategies and provide a systemic overview of two approaches based on sequencing and function. Strategies based on protein structure modification, such as introducing disulfide bonds, proline, salt bridges, -glycosylation modification, and truncation of loop structures, have already been summarized. This review discusses four aspects of cellulase-assisted extraction. Initially, cellulase alone was used to extract bioactive substances, and later, mixed enzyme systems were developed. Physical methods such as ultrasound, microwave, and high hydrostatic pressure have assisted in improving extraction efficiency. Cellulase changes the structure of biomolecules during the extraction process to convert them into effective ingredients with better activity and bioavailability. The combination of cellulase with other enzymes and physical technologies is a promising strategy for future extraction applications.
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http://dx.doi.org/10.3390/cimb43020050DOI Listing
July 2021

Comparison of the transoral endoscopic thyroidectomy vestibular approach and open thyroidectomy: A propensity score-matched analysis of surgical outcomes and safety in the treatment of papillary thyroid carcinoma.

Surgery 2021 Jul 17. Epub 2021 Jul 17.

Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, China.

Background: The transoral endoscopic thyroidectomy vestibular approach has been demonstrated to have similar surgical outcomes as open thyroidectomy for selected papillary thyroid carcinomas. This study aimed to evaluate and compare the surgical outcomes and safety of the transoral endoscopic thyroidectomy vestibular approach with those of open thyroidectomy in the treatment of papillary thyroid carcinoma with a diameter between >1 cm and ≤3.5cm.

Methods: We retrospectively reviewed all patients who had papillary thyroid carcinoma that was between >1 cm and ≤3.5 cm in diameter and who had undergone the transoral endoscopic thyroidectomy vestibular approach (n = 96) or an open thyroidectomy (n = 425) from January 2017 to June 2020. We then performed 1:1 propensity score matching, yielding 78 matched pairs. Afterward, surgical outcomes and follow-up data were compared between the 2 matched groups.

Results: Compared with the matched open thyroidectomy group, the papillary thyroid carcinoma group had a significantly longer operative time (P < .001), more blood loss (P < .05), higher postoperative white blood cell count (P < .05), higher C-reactive protein (P < .001), more total drainage volume (P < .001), increased surgical cost (P < .05), better cosmetic satisfaction (P <.001), lower scar self-consciousness (P < .001), and better quality of life (P < .001). We observed no significant differences in the incidence of other outcomes, including the number of retrieved lymph nodes and metastatic central lymph nodes, the rate of intraoperative recurrent laryngeal nerve signal weakened and parathyroid autotransplantation, visual analog scale scores for pain, drainage duration, postoperative hospital stay, rate of complications, and oncologic completeness. We observed no conversion to open thyroidectomy and no intraoperative capsular disruption in the transoral endoscopic thyroidectomy vestibular approach group. There was 1 case of persistent nodal disease in the transoral endoscopic thyroidectomy vestibular approach group. No recurrence was observed in the 2 groups during the follow-up period.

Conclusion: The transoral endoscopic thyroidectomy vestibular approach is feasible in selected patients with papillary thyroid carcinoma, not only because it is cosmetically advantageous but also because it is surgical and oncologically safe and may be an optional surgical method for treating papillary thyroid carcinomas having a diameter between >1 cm and ≤3.5 cm.
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http://dx.doi.org/10.1016/j.surg.2021.06.032DOI Listing
July 2021

A concise review: the synergy between artificial intelligence and biomedical nanomaterials that empowers nanomedicine.

Biomed Mater 2021 Jul 19. Epub 2021 Jul 19.

Michigan State University College of Human Medicine, 766 Service Rd., Rm. 2020, East Lansing, Michigan, 48824, UNITED STATES.

Nanomedicine has recently experienced unprecedented growth and development. However, the complexity of operations at the nanoscale introduces a layer of difficulty in the clinical translation of nanodrugs and biomedical nanotechnology. This problem is further exacerbated when engineering and optimizing nanomaterials for biomedical purposes. To navigate this issue, artificial intelligence algorithms have been applied for data analysis and inference, allowing for a more applicable understanding of the complex interaction amongst the abundant variables in a system involving the synthesis or use of nanomedicine. Here, we report on the current relationship and implications of nanomedicine and artificial intelligence. Particularly, we explore artificial intelligence as a tool for enabling nanomedicine in the context of nanodrug screening and development, brain machine interfaces and nanotoxicology. We also report on the current state and future direction of nanomedicine and artificial intelligence in cancer, diabetes, and neurological disorder therapy.
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http://dx.doi.org/10.1088/1748-605X/ac15b2DOI Listing
July 2021

Spin Crossover in a Series of Non-Hofmann-Type Fe(II) Coordination Polymers Based on [Hg(SeCN)] or [Hg(SeCN)] Building Blocks.

Inorg Chem 2021 Jul 19. Epub 2021 Jul 19.

College of Chemical and Chemical Engineering, Shandong University of Technology, Zibo 255049, People's Republic of China.

Self-assembly of [Hg(SeCN)] tetrahedral building blocks, iron(II) ions, and a series of bis-monodentate pyridyl-type bridging ligands has afforded the new heterobimetallic Hg-Fe coordination polymers {Fe[Hg(SeCN)](4,4'-bipy)} (), {Fe[Hg(SeCN)](tvp)} (), {Fe[Hg(SeCN)](4,4'-azpy)} (), {Fe[Hg(SeCN)](4,4'-azpy)(MeOH)} (), {Fe[Hg(SeCN)](3,3'-bipy)} () and {Fe[Hg(SeCN)](3,3'-azpy)} () (4,4-bipy = 4,4'-bipyridine, tvp = -1,2-bis(4-pyridyl)ethylene, 4,4'-azpy = 4,4'-azobispyridine, 3,3-bipy = 3,3'-bipyridine, 3,3'-azpy = 3,3'-azobispyridine). Single-crystal X-ray analyses show that compounds and display a two-dimensional robust sheet structure made up of infinite linear [(FeL)] (L = 4,4'-bipy or 4,4'-azpy) chains linked by formed {[Hg(L)(SeCN)]} anionic dimeric bridges. Complexes and - define three-dimensional networks with different topological structures, indicating, in combination with complexes and , that the polarity, length, rigidity, and conformation of the bridging organic ligand play important roles in the structural nature of the products reported here. The magnetic properties of complexes and show the occurrence of temperature- and light-induced spin crossover (SCO) properties, while complexes - are in the high-spin state at all temperatures. The current results provide a new route for the design and synthesis of new SCO functional materials with non-Hofmann-type traditional structures.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00802DOI Listing
July 2021

Antidepressant mechanism and active compounds of saffron from network pharmacology study.

Pak J Pharm Sci 2021 Mar;34(2):537-544

College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.

Saffron has been applied in depression treatment, but its antidepressant compounds and mechanisms are unclear. In this research, a network pharmacology-based method was proposed to screen the active compounds and the potential mechanisms of saffron for depression treatment. Firstly, the chemical compounds of saffron were collected from literature and filtered by drug-like prediction. Secondly, common targets, by comparing the targets of saffron predicted by Pharm Mapper server with targets associated with depression collected from Genecards, were regarded as the antidepressant targets of saffron. Thirdly, common targets were mapped to KEGG pathways, considered as the pathways related with the antidepressant effects of saffron. Finally, the network of compounds-targets-pathways was constructed and analyzed by cytoscape 3.4.0. Ten compounds including crocetin, picrocrocin, (1R, 5S, 6R)-5-(hydroxymethyl)- 4, 4, 6-trimethyl-7-Oxabicyclo[4.1.0]heptan-2-one and its glycoside were screened as the main antidepressant compounds, some of which were reported for the first time. They might have effective treatment for depression by acting on targets, such as MAP2K1, MAPK1, HRAS, PIK3R1, ALB and AKT1 and pathways related with immune system, signal transduction and so on. This study provided a new insight into the antidepressant mechanism and active compounds of saffron, which also had a guiding effect on later experiments.
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March 2021

Self-paced and self-consistent co-training for semi-supervised image segmentation.

Med Image Anal 2021 Jun 26;73:102146. Epub 2021 Jun 26.

Department of Software and IT Engineering, Ecole de technologie supérieure, Montreal, H3C1K3, Canada. Electronic address:

Deep co-training has recently been proposed as an effective approach for image segmentation when annotated data is scarce. In this paper, we improve existing approaches for semi-supervised segmentation with a self-paced and self-consistent co-training method. To help distillate information from unlabeled images, we first design a self-paced learning strategy for co-training that lets jointly-trained neural networks focus on easier-to-segment regions first, and then gradually consider harder ones. This is achieved via an end-to-end differentiable loss in the form of a generalized Jensen Shannon Divergence (JSD). Moreover, to encourage predictions from different networks to be both consistent and confident, we enhance this generalized JSD loss with an uncertainty regularizer based on entropy. The robustness of individual models is further improved using a self-ensembling loss that enforces their prediction to be consistent across different training iterations. We demonstrate the potential of our method on three challenging image segmentation problems with different image modalities, using a small fraction of labeled data. Results show clear advantages in terms of performance compared to the standard co-training baselines and recently proposed state-of-the-art approaches for semi-supervised segmentation.
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http://dx.doi.org/10.1016/j.media.2021.102146DOI Listing
June 2021

A global longitudinal strain cut-off value to predict adverse outcomes in individuals with a normal ejection fraction.

ESC Heart Fail 2021 Jul 17. Epub 2021 Jul 17.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, PO Box 5800, Maastricht, 6202 AZ, The Netherlands.

Aims: Global longitudinal strain (GLS) has become an alternative to left ventricular ejection fraction (LVEF) to determine systolic function of the heart. The absence of cut-off values is one of the limitations preventing full clinical implementation. The aim of this study is to determine a cut-off value of GLS for an increased risk of adverse events in individuals with a normal LVEF.

Methods And Results: Echocardiographic images of 502 subjects (52% female, mean age 48 ± 15) with an LVEF ≥ 55% were analysed using speckle tracking-based GLS. The primary endpoint was cardiovascular death or cardiac hospitalization. The analysis of Cox models with splines was performed to visualize the effect of GLS on outcome. A cut-off value was suggested by determining the optimal specificity and sensitivity. The median GLS was -22.2% (inter-quartile range -20.0 to -24.9%). In total, 35 subjects (7%) had a cardiac hospitalization and/or died because of cardiovascular disease during a follow-up of 40 (5-80) months. There was a linear correlation between the risk for adverse events and GLS value. Subjects with a normal LVEF and a GLS between -22.9% and -20.9% had a mildly increased risk (hazard ratio 1.01-2.0) for cardiac hospitalization or cardiovascular mortality, and the risk was doubled for subjects with a GLS of -20.9% and higher. The optimal specificity and sensitivity were determined at a GLS value of -20.0% (hazard ratio 2.49; 95% confidence interval: 1.71-3.61).

Conclusions: There is a strong correlation between cardiac adverse events and GLS values in subjects with a normal LVEF. In our single-centre study, -20.0% was determined as a cut-off value to identify subjects at risk. A next step should be to integrate GLS values in a multi-parametric model.
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http://dx.doi.org/10.1002/ehf2.13465DOI Listing
July 2021

Programmed cell death protein-1 (PD-1) protects liver damage by suppressing IFN-γ expression in T cells in infants and neonatal mice.

BMC Pediatr 2021 Jul 16;21(1):317. Epub 2021 Jul 16.

Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Children's Medical Research Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China.

Background: Biliary atresia (BA) is a severe cholangiopathy possibly resulting from virus-induced and immune-mediated injury of the biliary system. IFN-γ, secreted from CD4 Th1 cells and CD8 cytotoxic T cells, is a major mediator of liver pathology. Programmed death protein-1 (PD-1) signaling suppresses T cell function. However, how PD-1 modify T cell function in BA remains incompletely understood.

Methods: Frequencies of PD-1 expressing CD4 and CD8 T cells were analyzed in the liver and blood from BA and control subjects. Associations of PD-1CD4/CD8T cell abundances with liver function indices were measured. Function of PD-1 was measured by administration of an anti-PD-1 antibody in a Rhesus Rotavirus (RRV)-induced BA model. Survival, histology, direct bilirubin, liver immune cell subsets and cytokine production were analyzed.

Results: PD-1 was significantly upregulated in CD4 and CD8 T cells in patients with BA compared with control subjects. PD-1 expression in T cells was negatively associated with IFN-γ concentration in liver (PD-1CD4T cells in liver vs. IFN-γ concentration, r = - 0.25, p = 0.05; PD-1CD8T cells in liver vs. IFN-γ concentration, r = - 0.39, p = 0.004). Blockade of PD-1 increased IFN-γ expression in CD4 T and CD8 T cells (RRV vs. anti-PD-1 treated RRV mice: 11.59 ± 3.43% vs. 21.26 ± 5.32% IFN-γ in hepatic CD4T cells, p = 0.0003; 9.33 ± 4.03% vs. 22.55 ± 7.47% IFN-γ in hepatic CD8T cells, p = 0.0001), suppressed bilirubin production (RRV vs. anti-PD-1 treated RRV mice: 285.4 ± 47.93 vs. 229.8 ± 45.86 μmol/L total bilirubin, p = 0.01) and exacerbated liver immunopathology.

Conclusions: PD-1 plays a protective role in infants with BA by suppressing IFN-γ production in T cells. Increasing PD-1 signaling may serve as a therapeutic strategy for BA.
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http://dx.doi.org/10.1186/s12887-021-02794-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284022PMC
July 2021

Anesthetic Propofol Promotes Tumor Metastasis in Lungs via GABA R-Dependent TRIM21 Modulation of Src Expression.

Adv Sci (Weinh) 2021 Jul 15:e2102079. Epub 2021 Jul 15.

Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.

Generation of circulating tumor cells (CTCs), a key step in tumor metastasis, occurs during surgical tumor resection, often performed under general anesthesia. Propofol is the commonly used anesthetic, but its effects on CTCs and tumor metastasis remain largely unknown. Propofol effects are investigated in an experimental metastasis model by injecting tumor cells and, subsequently, low- or standard-dose propofol to nude mice through tail vein. Propofol- or vehicle-treated tumor cells are also injected to the mice. An in vitro tumor cell-vascular endothelial cell adhesion assay, immunofluorescence, and other methods are employed to assess how propofol affects tumor cell adhesion and extension. Propofol induces more lung tumor metastasis in mice than control. Mechanistically, propofol enhances tumor cell adhesion and extension through GABA R to downregulate TRIM21 expression, leading to upregulation of Src, a protein associated with cell adhesion. These results demonstrate that propofol may promote tumor metastasis through GABA R-TRIM21-Src mechanism.
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http://dx.doi.org/10.1002/advs.202102079DOI Listing
July 2021

The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis.

J Mol Med (Berl) 2021 Jul 13. Epub 2021 Jul 13.

Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA.

Pulmonary fibrosis is a chronic debilitating condition characterized by progressive deposition of connective tissue, leading to a steady restriction of lung elasticity, a decline in lung function, and a median survival of 4.5 years. The leading causes of pulmonary fibrosis are inhalation of foreign particles (such as silicosis and pneumoconiosis), infections (such as post COVID-19), autoimmune diseases (such as systemic autoimmune diseases of the connective tissue), and idiopathic pulmonary fibrosis. The therapeutics currently available for pulmonary fibrosis only modestly slow the progression of the disease. This review is centered on the interplay of damage-associated molecular pattern (DAMP) molecules, Toll-like receptor 4 (TLR4), and inflammatory cytokines (such as TNF-α, IL-1β, and IL-17) as they contribute to the pathogenesis of pulmonary fibrosis, and the possible avenues to develop effective therapeutics that disrupt this interplay.
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http://dx.doi.org/10.1007/s00109-021-02113-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277227PMC
July 2021

Hybrid Integrated Cardiomyocyte Biosensors for Bitter Detection and Cardiotoxicity Assessment.

ACS Sens 2021 Jul 12;6(7):2593-2604. Epub 2021 Jul 12.

Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China.

Among basic taste sensations, bitter taste is vital to the survival of mammals due to its indispensable role in toxin prediction or identification, so the identification of bitter compounds is of great value in the pharmaceutical and food industry. Recently, bitter taste receptor (T2Rs)-based biosensors have been developed for specific bitter detection. However, the taste biosensors based on taste cells/tissues suffer from simple function, low sensitivity, low content, and limited parameters. Here, to establish a high-content, highly sensitive, and multifunctional taste biosensor, we developed a multifunctional hybrid integrated cardiomyocyte biosensor (HICB) for bitter detection. Due to the expression of bitter taste receptors in cardiomyocytes, the HICB can recognize the specific bitter agonists by synchronously recording the extracellular field potential (EFP) and mechanical beating (MB) signals from the cultured cardiomyocytes in vitro. Multiple feature parameters were defined and extracted from the electromechanical signals of cardiomyocytes to analyze the specific responses to four typical bitter compounds. The radar map, heat map, and principal component analysis (PCA) were used to visualize and classify the specific responses. Moreover, bitter-induced cardiotoxicity also was chronically evaluated, and these bitter compounds presented an inhibition effect on the electrophysiological and contractile activities of cardiomyocytes. This high-content HICB offers an alternative platform for both bitter detection and cardiotoxicity assessment, showing promising applications in the fields of taste detection and toxicity screening.
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http://dx.doi.org/10.1021/acssensors.1c00158DOI Listing
July 2021

Rapid Antibacterial Effects of Silk Fabric Constructed through Enzymatic Grafting of Modified PEI and AgNP Deposition.

ACS Appl Mater Interfaces 2021 Jul 12;13(28):33505-33515. Epub 2021 Jul 12.

Key Laboratory of Science and Technology of Eco-Textile, Ministry of Education, Jiangnan University, Wuxi 214122, China.

Enzymatic antibacterial finishing is an eco-friendly alternative to develop functional silk-based materials. However, the low accessibility of tyrosine residues distributed in fibroin chains restricts the laccase-mediated functionalization of silk fibers (SF). To address this issue, a highly reactive -hydroxyphenylacetic acid-modified polyethyleneimine (mPEI) was enzymatically grafted onto fibroin using laccase, aiming at constructing an antibacterial matrix of mPEI on the fiber surface. Subsequently, in situ deposition of silver nanoparticles (i.e., AgNPs) into the newly built mPEI network was performed to form a rapid antibacterial layer. The results indicated that laccase efficiently catalyzes the mPEI coupling, the zeta potential of SF--mPEI increases from -32 to 21.70 mV, and the silver content reaches 1.81% after AgNP embedment. Based on the combined two-step treatments, the obtained silk fabric exhibited excellent antibacterial abilities against two bacteria, including () and (). The antibacterial rates of both bacteria reached 99.9% within 30 min of contact, remaining over 99.9% within 18 h of contact even after washing 10 times. The present work provides an enzyme-mediated method for construction of silk fabric with durable and rapid antibacterial activity.
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http://dx.doi.org/10.1021/acsami.1c08119DOI Listing
July 2021

Vorinostat ameliorates IL-1α-induced reduction of type II collagen by inhibiting the expression of ELF3 in chondrocytes.

J Biochem Mol Toxicol 2021 Jul 11:e22844. Epub 2021 Jul 11.

Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China.

Osteoarthritis (OA) is a common joint disease that ultimately causes physical disability and imposes an economic burden on society. Cartilage destruction plays a key role in the development of OA. Vorinostat is an oral histone deacetylase (HDAC) inhibitor and has been used for the treatment of T-cell lymphoma. Previous studies have reported the anti-inflammatory effect of HDAC inhibitors in both in vivo and in vitro models. However, it is unknown whether vorinostat exerts a protective effect in OA. In this study, our results demonstrate that treatment with vorinostat prevents interleukin 1α (IL-1α)-induced reduction of type II collagen at both gene and protein levels. Treatment with vorinostat reduced the IL-1α-induced production of mitochondrial reactive oxygen species (ROS) in T/C-28a2 cells. Additionally, vorinostat rescued the IL-1α-induced decrease in the expression of the collagen type II a1 (Col2a1) gene and the expression of Sry-related HMG box 9 (SOX-9). Importantly, we found that vorinostat inhibited the expression of matrix metalloproteinase-13 (MMP-13), which is responsible for the degradation of type II collagen. Furthermore, vorinostat suppressed the expression of E74-like factor 3 (ELF3), which is a key transcription factor that plays a pivotal role in the IL-1α-induced reduction of type II collagen. Also, the overexpression of ELF3 abolished the protective effects of vorinostat against IL-1α-induced loss of type 2 collagen by inhibiting the expression of SOX-9 whilst increasing the expression of MMP-13. In conclusion, our findings suggest that vorinostat might prevent cartilage destruction by rescuing the reduction of type II collagen, mediated by the suppression of ELF3.
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http://dx.doi.org/10.1002/jbt.22844DOI Listing
July 2021

The Non-Steroidal Mineralocorticoid Receptor Antagonist KBP-5074 Limits Albuminuria and has Improved Therapeutic Index Compared With Eplerenone in a Rat Model With Mineralocorticoid-Induced Renal Injury.

Front Pharmacol 2021 24;12:604928. Epub 2021 Jun 24.

KBP BioSciences USA Inc., Princeton, NJ, United States.

The therapeutic indices (TIs) and efficacy of the non-steroidal mineralocorticoid receptor antagonist (MRA) KBP-5074 and steroidal MRA eplerenone were evaluated in a uninephrectomized Sprague Dawley rat model of aldosterone-mediated renal disease. In two parallel studies, rats were placed on a high-salt diet and received aldosterone by osmotic mini-pump infusion over the course of 27 days. The urinary albumin-to-creatinine ratio (UACR) was evaluated after 7, 14, and 26 days of treatment. Serum K was evaluated after 14 and 27 days of treatment. Urinary Na, urinary K, and urinary Na/K ratio were evaluated after 7, 14, and 26 days of treatment. The TI was calculated for each drug as the ratio of the concentration of drug producing 50% of maximum effect (EC) for increasing serum K to the EC for lowering UACR. The TIs were 24.5 for KBP-5074 and 0.620 for eplerenone, resulting in a 39-fold improved TI for KBP-5074 compared with eplerenone. Aldosterone treatment increased UACR, decreased serum K, and decreased urinary Na relative to sham-operated controls that did not receive aldosterone infusion in both studies, validating the aldosterone/salt renal injury model. KBP-5074 prevented the increase in UACR at 0.5, 1.5, and 5 mg/kg BID while eplerenone did so only at the two highest doses of 50 and 450 mg/kg BID. Both KBP-5074 and eplerenone blunted the reduction in serum K seen in the aldosterone treatment group, with significant increases in serum K at the high doses only (5 mg/kg and 450 mg/kg BID, respectively). Additionally, the urinary Na and Na/K ratio significantly increased at the middle and high doses of KBP-5074, but only at the highest dose of eplerenone. These results showed increased TI and efficacy for KBP-5074 compared with eplerenone over a wider therapeutic window.
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http://dx.doi.org/10.3389/fphar.2021.604928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264204PMC
June 2021

Development of colloidal gold-based test strip for rapid detection of serotype 4 fowl adenovirus.

J Virol Methods 2021 Jul 7;296:114231. Epub 2021 Jul 7.

Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, Jiangsu, 225009, China. Electronic address:

The outbreaks of hepatitis-hydropericardium syndrome (HPS) caused by serotype 4 fowl adenovirus (FAdV-4) have spread from broilers to laying hens, breeders, geese and Cherry Valley duck, resulting in high economic losses to the poultry industry globally. In this study, a rapid colloidal gold test strip for detection of FAdV-4 was developed by using two monoclonal antibodies (mAbs) against the Fiber-2 of FAdV-4. Specificity analysis revealed that the test strip only reacted with FAdV-4, but not with other pathogens including different serotypes of fowl adenovirus and other avian pathogens tested. The limit of the detection (LOD) of the strip could reach as low as 0.1 μg/0.1 mL of GST-Fiber-2 protein and 1 × 10 TCID/0.1 mL of FAdV-4, respectively. Moreover, the test strip could be efficiently applied in detecting tissue samples from diseased chickens with HPS. Comparison analysis further revealed that the test strip showed good compatibility with PCR assay for detection of virus isolates and clinical samples. In conclusion, our test strip provides an efficient on-site diagnostic method in a quick and convenient manner for detection of FAdV-4, especially in resource-limited areas.
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http://dx.doi.org/10.1016/j.jviromet.2021.114231DOI Listing
July 2021

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke.

Front Med 2021 Jul 9. Epub 2021 Jul 9.

Department of Nuclear Medicine and Medical PET Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.
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http://dx.doi.org/10.1007/s11684-021-0842-9DOI Listing
July 2021

Study on the application effect of personalized nursing in the operating room of laparoscopic cholecystectomy for gallstone.

Panminerva Med 2021 Jul 9. Epub 2021 Jul 9.

Central Ward Operating Room, Yantai Yuhuangding Hospital, Yantai, China -

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http://dx.doi.org/10.23736/S0031-0808.21.04419-0DOI Listing
July 2021

Precise Encoding of Triple-bond Raman Scattering of Single Polymer Nanoparticles for Multiplexed Imaging Application.

Angew Chem Int Ed Engl 2021 Jul 6. Epub 2021 Jul 6.

Wuhan University, College of Life Sciences, CHINA.

Stimulated Raman scattering (SRS) microscopy in combination with innovative tagging strategies offers great potential as a universal high-throughput biomedical imaging tool. Here, we report on rationally tailored small molecular monomers containing triple-bond units with large Raman scattering cross-sections, which can be polymerized at the nanoscale for enhancement of SRS contrast with smaller but brighter optical nanotags with artificial 'fingerprint' output. From this, a class of triple-bond rich polymer nanoparticles (NPs) was engineered by regulating the relative dosages of three chemically different triple-bond monomers in co-polymerization. The suggested bonding strategy allowed for 15 spectrally distinguishable triple-bond combinations. These accurately structured nano molecular aggregates, rather than long-chain macromolecules, could establish a universal method for generating small-sized biological SRS imaging tags with high-sensitivity for high-throughput multi-color biomedical imaging.
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http://dx.doi.org/10.1002/anie.202106136DOI Listing
July 2021

m6A modification promotes miR-133a repression during cardiac development and hypertrophy via IGF2BP2.

Cell Death Discov 2021 Jun 26;7(1):157. Epub 2021 Jun 26.

Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, 325027, Zhejiang, PR China.

Both N6-methyladenosine (m6A) RNA modification and microRNAs (miRNAs) are common regulatory mechanisms for gene post-transcription by modulating mRNA stability and translation. They also share the same 3'-untranslated regions (UTRs) regions for their target gene. However, little is known about their potential interaction in cell development and biology. Here, we aimed to investigate how m6A regulates the specific miRNA repression during cardiac development and hypertrophy. Our multiple lines of bioinformatic and molecular biological evidence have shown that m6A modification on cardiac miR-133a target sequence promotes miR-133a repressive effect via AGO2-IGF2BP2 (Argonaute 2-Insulin-like growth factor 2 mRNA binding protein 2) complex. Among 139 cardiac miRNAs, only the seed sequence of miR-133a was inversely complement to m6A consensus motif "GGACH" by sequence alignment analysis. Immunofluorescence staining, luciferase reporter, and m6A-RIP (RNA immunoprecipitation) assays revealed that m6A modification facilitated miR-133a binding to and repressing their targets. The inhibition of the miR-133a on cardiac proliferation and hypertrophy could be prevented by silencing of Fto (FTO alpha-ketoglutarate dependent dioxygenase) which induced m6A modification. IGF2BP2, an m6A binding protein, physically interacted with AGO2 and increased more miR-133a accumulation on its target site, which was modified by m6A. In conclusion, our study revealed a novel and precise regulatory mechanism that the m6A modification promoted the repression of specific miRNA during heart development and hypertrophy. Targeting m6A modification might provide a strategy to repair hypertrophic gene expression induced by miR-133a.
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http://dx.doi.org/10.1038/s41420-021-00552-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257704PMC
June 2021
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