Publications by authors named "Li Mei"

1,928 Publications

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Aptamer-based biosensors for the diagnosis of sepsis.

J Nanobiotechnology 2021 Jul 19;19(1):216. Epub 2021 Jul 19.

Institute for Translational Medicine, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 266003, China.

Sepsis, the syndrome of infection complicated by acute organ dysfunction, is a serious and growing global problem, which not only leads to enormous economic losses but also becomes one of the leading causes of mortality in the intensive care unit. The detection of sepsis-related pathogens and biomarkers in the early stage plays a critical role in selecting appropriate antibiotics or other drugs, thereby preventing the emergence of dangerous phases and saving human lives. There are numerous demerits in conventional detection strategies, such as high cost, low efficiency, as well as lacking of sensitivity and selectivity. Recently, the aptamer-based biosensor is an emerging strategy for reasonable sepsis diagnosis because of its accessibility, rapidity, and stability. In this review, we first introduce the screening of suitable aptamer. Further, recent advances of aptamer-based biosensors in the detection of bacteria and biomarkers for the diagnosis of sepsis are summarized. Finally, the review proposes a brief forecast of challenges and future directions with highly promising aptamer-based biosensors.
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http://dx.doi.org/10.1186/s12951-021-00959-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287673PMC
July 2021

A Computational Tumor-Infiltrating Lymphocyte Assessment Method Comparable with Visual Reporting Guidelines for Triple-Negative Breast Cancer.

EBioMedicine 2021 Jul 16;70:103492. Epub 2021 Jul 16.

Bio-totem Pte Ltd, Foshan, P. R. China; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China. Electronic address:

Background: Tumor-infiltrating lymphocytes (TILs) are clinically significant in triple-negative breast cancer (TNBC). Although a standardized methodology for visual TILs assessment (VTA) exists, it has several inherent limitations. We established a deep learning-based computational TIL assessment (CTA) method broadly following VTA guideline and compared it with VTA for TNBC to determine the prognostic value of the CTA and a reasonable CTA workflow for clinical practice.

Methods: We trained three deep neural networks for nuclei segmentation, nuclei classification and necrosis classification to establish a CTA workflow. The automatic TIL (aTIL) score generated was compared with manual TIL (mTIL) scores provided by three pathologists in an Asian (n = 184) and a Caucasian (n = 117) TNBC cohort to evaluate scoring concordance and prognostic value.

Findings: The intraclass correlations (ICCs) between aTILs and mTILs varied from 0.40 to 0.70 in two cohorts. Multivariate Cox proportional hazards analysis revealed that the aTIL score was associated with disease free survival (DFS) in both cohorts, as either a continuous [hazard ratio (HR)=0.96, 95% CI 0.94-0.99] or dichotomous variable (HR=0.29, 95% CI 0.12-0.72). A higher C-index was observed in a composite mTIL/aTIL three-tier stratification model than in the dichotomous model, using either mTILs or aTILs alone.

Interpretation: The current study provides a useful tool for stromal TIL assessment and prognosis evaluation for patients with TNBC. A workflow integrating both VTA and CTA may aid pathologists in performing risk management and decision-making tasks.
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http://dx.doi.org/10.1016/j.ebiom.2021.103492DOI Listing
July 2021

MiR-375-3p mediates reduced pineal function in hypoxia-ischemia brain damage.

Exp Neurol 2021 Jul 17;344:113814. Epub 2021 Jul 17.

Department of Neonatology, Children's Hospital of Soochow University, Suzhou 215000, China. Electronic address:

The functional roles of microRNAs (miRNAs) have been studied in various diseases, including hypoxic-ischemic brain damage (HIBD). However, changes in the expression of miRNAs and the underlying mechanisms in the pineal gland during HIBD remain unknown. Based on the previous study by microRNA array, hundreds of miRNAs showed altered expression patterns in the pineal gland in a rat model of HIBD. MiR-375-3p was found to be significantly upregulated and abundant in the pineal gland. Further investigation in an in vitro HI model of pinealocytes showed that miRNA-375 exacerbated the damage to pineal function. After oxygen-glucose deprivation / reoxygenation (OGD/R), miR-375-3p expression increased, while aralkylamine N-acetyltransferase (AANAT) expression and melatonin (MT) secretion decreased. Overexpression of miRNA-375 in pinealocytes aggravated the influence of OGD/R on AANAT expression and MT secretion. Because miRNA-375 overexpression in pinealocytes induced decreased rasd1 mRNA and protein expression, rasd1 may mediate the effect of miR-375-3p on pineal function. Furthermore, miR-375-3p aggravated the cognitive impairment caused by HIBD in rats, as observed by Morris water maze test, and also affected emotion and circadian rhythm in HIBD-treated rats. Thus, miR-375-3p may be a key regulatory molecule in the pineal gland following HIBD, and targeting of miR-375-3p may represent a new strategy for the treatment of HIBD.
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http://dx.doi.org/10.1016/j.expneurol.2021.113814DOI Listing
July 2021

Changes in serum calcium and treatment of hypoparathyroidism during pregnancy and lactation: A single-center case series.

J Clin Endocrinol Metab 2021 Jul 19. Epub 2021 Jul 19.

Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Background: Hypoparathyroidism (Hypo-PT) is rare, and studies on Hypo-PT, especially during pregnancy and lactation, are limited.

Design And Setting: This was a retrospective study on a relatively large case series in a single center from mainland China.

Methods: A total of 19 patients with 25 pregnancies, diagnosed with Hypo-PT before pregnancy, were enrolled. Data on clinical characteristics and treatment strategies at onset time and around pregnancy period were collected.

Results: During pregnancy, except two patients with missing data, five patients with six pregnancies (6/23, 26.1%) experienced improved Hypo-PT condition, defined as an increased serum calcium level; four patients with four pregnancies (4/23, 17.4%) experienced worsened Hypo-PT condition, defined as a more than 0.2 mmol/L decline in the serum calcium level; and three patients with three pregnancies (3/23, 13.0%) remained in stable Hypo-PT condition. The prevalence of adverse pregnancy outcomes was 30.4% (4/23 for preterm delivery; 3/23 for miscarriage). The serum Ca and 24-hUCa levels significantly increased during lactation compared with pregnancy (2.57 ± 0.34 vs 1.99 ± 0.11 mmol/L, P < 0.001; 12.28 ± 5.41 vs 8.63 ± 3.22 mmol/L, P = 0.013), and five patients with five lactations (5/12, 41.7%) developed hypercalcemia in the first 2 months after delivery.

Conclusions: Female patients with Hypo-PT had different changes in calcium homeostasis and a high prevalence of adverse outcomes during pregnancy. Thus they should be monitored closely to maintain the optimal serum Ca level. Decreasing drug dosage during the lactation period should be considered to avoid hypercalcemia.
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http://dx.doi.org/10.1210/clinem/dgab530DOI Listing
July 2021

Comparative effect of eldecalcitol and alfacalcidol on bone microstructure: A preliminary report of secondary analysis of a prospective trial.

Osteoporos Sarcopenia 2021 Jun 3;7(2):47-53. Epub 2021 Jun 3.

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Objectives: To compare the effect of eldecalcitol and alfacalcidol on skeletal microstructure by high-resolution peripheral QCT (HR-pQCT).

Methods: This was a substudy of a randomized, double-blind, active comparator trial. Five female osteoporotic patients with 1-year 0.75 μg/day eldecalcitol and 5 with 1-year 1.0 μg/day alfacalcidol completed HR-pQCT scans before and after treatment were enrolled.

Results: Total vBMD [1.67 ± 1.06% (mean ± SD), P = 0.043 versus baseline] and trabecular vBMD (2.91 ± 1.72%, P = 0.043) at the radius increased in eldecalcitol group, while total, trabecular, and cortical vBMD tended to decrease in alfacalcidol group, with a significant reduction in cortical vBMD at the tibia (0.88 ± 0.62%, P = 0.043). Cortical area (1.82 ± 1.92%, P = 0.043) at the radius and thickness (0.87 ± 1.12%, P = 0.043) at the tibia increased in eldecalcitol group, while these parameters decreased with alfacalcidol at the tibia (1.77 ± 1.72%, P = 0.043 for cortical area; 1.40 ± 2.14%, P = 0.042 for cortical thickness). Trabecular thickness at the radius (1.97 ± 1.93%, P = 0.042) and number at the tibia (3.09 ± 3.04%, P = 0.043) increased by eldecalcitol but did not increase by alfacalcidol. Trabecular separation decreased by eldecalcitol (2.22 ± 2.43%, P = 0.043) but tended to increase by alfacalcidol at the tibia.

Conclusions: Eldecalcitol has the greater potential to improve cortical and trabecular microstructure at the peripheral bone than alfacalcidol which needs further more studies.
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http://dx.doi.org/10.1016/j.afos.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261726PMC
June 2021

Comparative analysis of bile culture and blood culture in patients with malignant biliary obstruction complicated with biliary infection.

J Cancer Res Ther 2021 Jul;17(3):726-732

Department of Intervention, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, Hebei Province, China.

Objective: This study is aimed to provide a clinical basis for the identification and treatment of patients with malignant biliary obstruction (MBO) complicated with biliary infection by comparing pathogenic bacteria detected in bile and blood cultures from these patients.

Materials And Methods: A total of 380 patients with MBO who received percutaneous transhepatic cholangic drainage from January 2004 to January 2019 were included in the study. A total of 90 patients were diagnosed with having MBO complicated with biliary infection, and bile and blood culture were simultaneously performed on these patients. The patients included 58 men and 32 women, ranging in age from 33 to 86 years old, with a mean age of 60.69 years.

Results: The detection rate using bile bacterial culture in patients with MBO complicated with biliary infection was significantly higher than that using blood culture, and there were significant differences in the two kinds of bacterial culture found positive bile and blood cultures from the same patients. Gram-positive cocci were dominant in the bile cultures and Gram-negative bacilli were dominant in the blood cultures. Therefore, it is necessary to conduct simultaneous bile bacterial culture and blood culture for patients with MBO complicated with biliary infection, especially those with severe or critical diseases.

Conclusions: It is vital to enable simultaneous bile bacterial culture and blood culture in patients with MBO complicated with biliary infection. Existing guidelines for the diagnosis and treatment of benign biliary infection are not applicable to patients with MBO complicated with biliary infection.
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http://dx.doi.org/10.4103/jcrt.JCRT_1705_20DOI Listing
July 2021

Artificial intelligence in digital cariology: a new tool for the diagnosis of deep caries and pulpitis using convolutional neural networks.

Ann Transl Med 2021 May;9(9):763

Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.

Background: An accurate diagnosis of deep caries and pulpitis on periapical radiographs is a clinical challenge.

Methods: A total of 844 radiographs were included in this study. Of the 844, 717 (85%) were used for training and 127 (15%) were used for testing the three convolutional neural networks (CNNs) (VGG19, Inception V3, and ResNet18). The performance [accuracy, precision, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC)] of the CNNs were evaluated and compared. The CNN model with the best performance was further integrated with clinical parameters to see whether multi-modal CNN could provide an enhanced performance. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique illustrates what image feature was the most important for the CNNs.

Results: The CNN of ResNet18 demonstrated the best performance [accuracy =0.82, 95% confidence interval (CI): 0.80-0.84; precision =0.81, 95% CI: 0.73-0.89; sensitivity =0.85, 95% CI: 0.79-0.91; specificity =0.82, 95% CI: 0.76-0.88; and AUC =0.89, 95% CI: 0.86-0.92], compared with VGG19 and Inception V3 as well as the comparator dentists. Therefore, ResNet18 was chosen to integrate with clinical parameters to produce the multi-modal CNN of ResNet18 + C, which showed a significantly enhanced performance (accuracy =0.86, 95% CI: 0.84-0.88; precision =0.85, 95% CI: 0.76-0.94; sensitivity =0.89, 95% CI: 0.83-0.95; specificity =0.86, 95% CI: 0.79-0.93; and AUC =0.94, 95% CI: 0.91-0.97).

Conclusions: The CNN of ResNet18 showed good performance (accuracy, precision, sensitivity, specificity, and AUC) for the diagnosis of deep caries and pulpitis. The multi-modal CNN of ResNet18 + C (ResNet18 integrated with clinical parameters) demonstrated a significantly enhanced performance, with promising potential for the diagnosis of deep caries and pulpitis.
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http://dx.doi.org/10.21037/atm-21-119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246233PMC
May 2021

Development and Validation of Prognostic Nomograms Based on Gross Tumor Volume and Cervical Nodal Volume for Nasopharyngeal Carcinoma Patients With Concurrent Chemoradiotherapy.

Front Oncol 2021 28;11:682271. Epub 2021 Jun 28.

Department of Radiation Oncology, Cancer Hospital, Shantou University Medical College, Shantou University, Shantou, China.

Purpose: Our study aimed to establish and validate prognostic nomograms based on gross tumor volume (GTV) and cervical nodal volume (CNV) for nasopharyngeal carcinoma (NPC) patients treated with two cycles of concurrent chemoradiotherapy (CCRT).

Methods: From 2012 to 2015, 620 eligible patients who received radical treatment at the Cancer Hospital of Shantou University Medical College were recruited for a nomogram study. Variables were determined in a training set of 463 patients from 2012 to 2014 by X-tile analysis, univariate and multivariate Cox proportional hazard analyses, and the least absolute shrinkage and selection operator (LASSO). Another cohort of 157 patients in 2015 was validated with bootstrap resampling. The concordance index (C-index) and calibration curves were applied to assess its predictive discriminative and accuracy ability, while decision curve analysis (DCA), X-tile analysis and Kaplan-Meier curve for clinical application.

Results: Independent prognostic variables for overall survival (OS) were age, GTV, CNV, cranial nerve, positive cervical lymph node laterality below the caudal border of cricoid cartilage (LNBC), and were selected for the nomogram. Optimal prognostic factors including Karnofsky performance status (KPS), age, GTV, CNV, LNBC were incorporated in the nomogram for progression-free survival (PFS). In the training set, the C-index of our nomograms for OS and PFS were 0.755 (95% CI, 0.704 to 0.807) and 0.698 (95% CI, 0.652 to 0.744). The calibration curve showed good agreement between nomogram-predicted and actual survival. DCA indicated that our nomograms were of clinical benefit.

Conclusion: Our nomograms are capable of effective prognostic prediction for patients with NPC.
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http://dx.doi.org/10.3389/fonc.2021.682271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273655PMC
June 2021

Structural basis of LhcbM5-mediated state transitions in green algae.

Nat Plants 2021 Jul 8. Epub 2021 Jul 8.

National Laboratory of Biomacromolecules, CAS Centre for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

In green algae and plants, state transitions serve as a short-term light-acclimation process in the regulation of the light-harvesting capacity of photosystems I and II (PSI and PSII, respectively). During the process, a portion of light-harvesting complex II (LHCII) is phosphorylated, dissociated from PSII and binds with PSI to form the supercomplex PSI-LHCI-LHCII. Here, we report high-resolution structures of PSI-LHCI-LHCII from Chlamydomonas reinhardtii, revealing the mechanism of assembly between the PSI-LHCI complex and two phosphorylated LHCII trimers containing all four types of LhcbM protein. Two specific LhcbM isoforms, namely LhcbM1 and LhcbM5, directly interact with the PSI core through their phosphorylated amino terminal regions. Furthermore, biochemical and functional studies on mutant strains lacking either LhcbM1 or LhcbM5 indicate that only LhcbM5 is indispensable in supercomplex formation. The results unravel the specific interactions and potential excitation energy transfer routes between green algal PSI and two phosphorylated LHCIIs.
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http://dx.doi.org/10.1038/s41477-021-00960-8DOI Listing
July 2021

Acupuncture Regulates Serum Differentially Expressed Proteins in Patients with Chronic Atrophic Gastritis: A Quantitative iTRAQ Proteomics Study.

Evid Based Complement Alternat Med 2021 14;2021:9962224. Epub 2021 Jun 14.

Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Objective: To identify differentially expressed proteins (DEPs) in sera of patients with chronic atrophic gastritis (CAG) using isobaric tags for relative and absolute quantitation (iTRAQ) and to explore acupuncture's mechanism in CAG.

Methods: Peripheral sera from 8 healthy volunteers (HC), 8 chronic nonatrophic gastritis (NAG) patients, 8 CAG patients, and 8 CAG patients who underwent acupuncture treatment (CAG + ACU) were collected followed by labeling with iTRAQ reagent for protein identification and quantification using two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS). Representative DEPs were selected through bioinformatics, and proteins were verified by enzyme-linked immunosorbent assay (ELISA).

Results: A total of 4,448 unique peptides were identified, corresponding to 816 nonredundant proteins. A 1.4-fold difference was used as the threshold. Compared with the HC group, 75 and 106 DEPs were identified from CAG and NAG groups, respectively. Compared with the CAG group, 110 and 66 DEPs were identified from the NAG and CAG + ACU groups, respectively. The DEPs were mainly involved in protein binding and the Notch signaling pathway-related proteins, and the upregulated proteins included actin-binding proteins (thymosin beta-4, tropomyosin-4, profilin-1, transgelin-2), while the downregulated proteins included Notch2 and Notch3. After acupuncture, the expression of these proteins in CAG patients was less differentiated from that in healthy people. The level of the above 6 proteins were verified by ELISA, and the results were similar to the results of iTRAQ analysis.

Conclusions: Actin-binding proteins and Notch signaling pathway-related proteins were correlated with the development and progression of CAG and thus are potential diagnostic markers for CAG. Acupuncture may play a role in regulating actin-binding proteins and Notch signaling pathway-related proteins to play a therapeutic role in CAG.
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http://dx.doi.org/10.1155/2021/9962224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219412PMC
June 2021

MiR-382-5p suppresses M1 macrophage polarization and inflammatory response in response to bronchopulmonary dysplasia through targeting CDK8: Involving inhibition of STAT1 pathway.

Genes Cells 2021 Jul 6. Epub 2021 Jul 6.

Department of Pediatrics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Bronchopulmonary dysplasia (BPD) is an inflammation-related respiratory disorder in infants. MiR-382-5p has displayed low expression in developing lungs with BPD, while the effect of miR-382-5p on BPD remains elusive. Here, a hyperoxia (85% oxygen)-induced BPD model in neonatal mice was established. On postnatal days 10 and 15, hyperoxia reduced miR-382-5p expression in lungs of mice. Besides, CDK8, CD68 and CD86 levels were elevated on day 15 after birth, implying the involvement of CDK8 in M1 macrophage polarization. In addition, in vitro injury in RAW264.7 macrophages was induced by IFN-γ and LPS stimulation. Lentivirus-encoding miR-382-5p decreased CDK8 expression, alleviated the production of inflammatory cytokines TNF-α, IL-1β and IL-6, and restricted the levels of CD40 and CD86 in response to IFN-γ and LPS. Moreover, miR-382-5p inhibited the phosphorylation of STAT1. Luciferase reporter assay verified that miR-382-5p might target the 3'UTR of CDK8. Rescue assays revealed that CDK8 reversed the mitigating roles of miR-382-5p in inflammatory response and M1 macrophage polarization, as reflected by increased IL-6 and CD40 levels. Taken together, these findings indicate that miR-382-5p may suppress M1 macrophage activation and inflammatory response via inhibiting CDK8, thereby regulating the development of BPD, which is possibly mediated by STAT1 signaling.
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http://dx.doi.org/10.1111/gtc.12883DOI Listing
July 2021

Designing water-quenching resistant highly luminescent europium complexes by regulating the orthogonal arrangement of bis-β-diketone ligands.

Dalton Trans 2021 Jul;50(28):9914-9922

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education; School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, P. R. China.

Luminescent β-diketone-based lanthanide complexes have been well explored as chemical sensor materials for biomedicine applications. Herein, three mononuclear Eu3+ complexes based on bis-β-diketone ligands (L1, L2 and L3) that can reduce luminescence quenching caused by water were developed. The ligands feature two β-diketone units covalently bound at the 1,8-position of the derivatized anthracene (modified with tetracyanoethylene, TCNE). X-ray crystallographic analysis reveals that their self-assemblies with Ln3+ ions in a 2 : 1 stoichiometric ratio form mononuclear anion complexes, [EuL2]-, in which two ligands coordinate to the metal center in a mutually orthogonal manner. This kind of arrangement together with the bulge of TCNE from the anthracene plane well protected the complexes from the quenching effects of water molecules in the second coordination. The photophysical measurements showed that the complexes not only had high luminescence quantum yields (QYs, up to 50-67%) but also presented excellent water-quenching resistant capability.
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http://dx.doi.org/10.1039/d1dt00155hDOI Listing
July 2021

Characterization of the clinical and genetic spectrum of autoimmune polyendocrine syndrome type 1 in Chinese case series.

Orphanet J Rare Dis 2021 Jul 3;16(1):296. Epub 2021 Jul 3.

Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Dongcheng District, Shuaifuyuan No.1, Beijing, 100730, China.

Background: Autoimmune polyendocrine syndrome type 1 (APS1) is a hereditary disease caused by mutations in the AIRE gene with both endocrine and non-endocrine organ involvement. The existing data from China are limited, and this study aims to describe the phenotypes and genetic characterization in Chinese APS1 patients. In this single-center, retrospective, observational study, comprehensive endocrine and extra-endocrine manifestations were collected, and genetic analysis in AIRE was conducted in patients with APS1 between the years of 1984 and 2018 at Peking Union Medical College Hospital.

Results: In total, 13 patients from 12 unrelated families were enrolled, seven of whom were female, with hypoparathyroidism, chronic mucocutaneous candidiasis, and Addison's disease being the most frequently observed manifestations. Up to 84.7% presented with two or three of the above-mentioned manifestations, and nearly 4.9 ± 1.8 components presented in patients aged 21.2 ± 7.9 years old. Several less common phenotypes, such as myeloproliferative disease, pure red cell aplasia, renal tubular acidosis, asplenia, autoimmune hepatitis, and ankylosing spondylitis, were also observed in patients. Altogether, seven different AIRE mutations were found in six patients, four of which (K161fs, G208V, A246fs, and L308F) had not been previously reported in patients with APS1.

Conclusion: We have provided a comprehensive profile of Chinese patients with APS1, with less commonly observed features being observed in addition to more regularly seen manifestations. Additionally, different AIRE mutations that were observed have expanded the genetic spectrum, which will help with future understanding of the molecular pathogenesis of APS1.
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http://dx.doi.org/10.1186/s13023-021-01933-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254246PMC
July 2021

Metabolic Profiles of Roots in Response to Cadmium Stress.

Metabolites 2021 Jun 13;11(6). Epub 2021 Jun 13.

Crop Research Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China.

has great application potential in phytoremediation of cadmium (Cd)-contaminated soil because of its excellent Cd accumulating and high biomass. In this study, we compared the effects of Cd under 48 h and 7 d stress in roots of using metabolite profiling. The results showed that many metabolic pathways and metabolites in roots were altered significantly in response to Cd stress. We found that significant differences in levels of amino acids, organic acids, carbohydrates, lipids, flavonoids, alkaloids, and indoles were induced by Cd stress at different times, which played a pivotal role in the adaptation of roots to Cd stress. Meanwhile, roots could resist 48 h Cd stress by regulating the biosynthesis of amino acids, linoleic acid metabolism, aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, ABC transporters, arginine biosynthesis, valine, leucine and isoleucine biosynthesis, and alpha-linolenic acid metabolism; however, they regulated alpha-linolenic acid metabolism, glycerophospholipid metabolism, ABC transporters, and linoleic acid metabolism to resist 7 d Cd stress. A metabolomic expedition to the response of to Cd stress will help to comprehend its tolerance and accumulation mechanisms of Cd.
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http://dx.doi.org/10.3390/metabo11060383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232002PMC
June 2021

Identification of functional lncRNAs through constructing a lncRNA-associated ceRNA network in myocardial infarction.

Math Biosci Eng 2021 May;18(4):4293-4310

Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

Myocardial infarction (MI) is a type of coronary heart disease, which refers to the ischemic necrosis of the heart muscle. A large number of studies have discussed the mechanism of MI from the perspective of competing endogenous RNA (ceRNA) network. However, the mechanisms underlying the function of lncRNAs in MI have still not been explained in an explicit manner. Therefore, we constructed a scale-free lncRNA-associated ceRNA network to identify some crucial lncRNAs in MI. Results showed that the given disease genes for MI were involved in the network, the degrees of which were significantly larger than the other nodes of the network. For measuring the network centrality, we then constructed a hub subnetwork. The miRNAs and mRNAs in the hub subnetwork have been validated to function in MI-related biological function. In addition, we identified 2 MI-related functional modules from the lncRNA-associated ceRNA network, which suggested that lncRNA exerted function in local network. Enrichment analysis showed that these functional modules corresponded to some similar and different pathways related to cardiovascular disease. More importantly, 3 MI-related crucial lncRNAs, CTD-3092A11.2, RP5-821D11.7 and CTC-523E23.1 were detected as potential biomarkers, which may be involved in MI-related biological progresses. Our study identified 20 functional lncRNAs based on ceRNA network analysis, which may provide novel diagnosis and therapeutic targets for MI from the ceRNA network perspective.
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http://dx.doi.org/10.3934/mbe.2021215DOI Listing
May 2021

Multiple Genetic Mutations Related to Insecticide Resistance are Detected in Field Kazakhstani House Flies (Muscidae: Diptera).

J Med Entomol 2021 Jul 1. Epub 2021 Jul 1.

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

The house fly (Musca domestica Linnaeus) is an important disease vector. Insecticide resistance is an obstacle to effective house fly control. Previous studies have demonstrated that point mutations in acetylcholinesterase (Ace), carboxylesterase (MdαE7) and voltage-sensitive sodium channel (Vssc), and over-expression of CYP6D1v1 confer insecticide resistance in the house fly. However, information about the status and underlying mechanisms of insecticide resistance in Kazakhstani house flies is lacking. In this study, we investigated the occurrence of genetic mutations associated with insecticide resistance in field house flies collected at six different locations in southern Kazakhstan. Four mutations (V260L, G342A/V, and F407Y) in Ace and three mutations (G137D and W251L/S) in MdαE7 were detected with appreciable frequencies. Notably, haplotypes carrying triple-loci mutations in Ace and double mutations in MdαE7 were found in Kazakhstan. The L1014H and L1014F mutations in Vssc, and CYP6D1v1 resistance allele were detected at a low frequency in some of the six investigated house fly populations. Phylogenetic analyses of haplotypes supported multiple origins of resistance mutations in Ace and MdαE7. These observations suggest that house flies in southern Kazakhstan may exhibit significant resistance to organophosphates and carbamates. Regular monitoring of insecticide resistance is recommended to achieve effective house fly control by chemical agents in southern Kazakhstan.
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http://dx.doi.org/10.1093/jme/tjab110DOI Listing
July 2021

Healthcare workers' (HCWs) attitudes and related factors towards COVID-19 vaccination: a rapid systematic review.

Postgrad Med J 2021 Jun 30. Epub 2021 Jun 30.

Department of Nursing, the Affiliated Hospital of Southwest Medical University, Luzhou, China

Herd immunity through vaccination is a key measure to control COVID-19 pandemic. However, vaccine hesitancy remains a public health threat, which is still common among healthcare workers (HCWs). This systematic review aimed to synthesise evidence on HCWs' attitudes towards COVID-19 vaccination and analyse associated factors to provide information for vaccine policy development and practice. We searched PubMed, Embase, ScienceDirect, Web of Science and three Chinese databases for literature published on 12 February 2021. Two researchers screened the literature independently, and 13 studies were included in the systematic review. Vaccine acceptance varied widely and ranged from 27.7% to 77.3%. HCWs had positive attitudes towards future COVID-19 vaccines, while vaccine hesitancy was still common. Demographic variables such as men, older age and physicians were positive predictive factors. Women and nurses had more vaccine hesitancy. Previous influenza vaccination and self-perceived risk were facilitators. Concerns for safety, efficacy and effectiveness and distrust of the government were barriers. Influences of direct (COVID-19) patient care towards vaccination intention were less conclusive. Tailored communication strategies were needed to increase the uptake rate of COVID-19 vaccines among HCWs. More importantly, more data and information on the safety and efficacy of vaccines should be provided with transparency.
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http://dx.doi.org/10.1136/postgradmedj-2021-140195DOI Listing
June 2021

Phosphate recovery from the P-enriched brine of AnMBR-RO-IE treating municipal wastewater via an innovated phosphorus recovery batch reactor with nano-sorbents.

Chemosphere 2021 Jun 25;284:131259. Epub 2021 Jun 25.

Advanced Environmental Biotechnology Centre, Nanyang Environment and Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, Singapore, 637141, Singapore; School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore. Electronic address:

Municipal wastewater is a very unique pool full of energy and useful substances. Though the innovative integrated anaerobic membrane bioreactor and reverse osmosis-ion exchange (AnMBR-RO-IE) process can produce high-grade reclaimed water with high energy efficiency, phosphorus resources recovery in the WWTPs has been rarely reported thus far. This study evaluated the feasibility of a phosphorus recovery batch reactor (PRBR) as an approach for the phosphate production from the P-enriched brine from AnMBR-RO-IE. With operating PRBR for 162 cycles, high to 85% of P recovery rate was obtained for 145 cycles, leading to a P production rate of 6.17 g/m domestic wastewater with nano-sorbents (NSs) consumption rate of 10.2 g/m. Acidification pretreatment efficiently improved the adsorption capacity and reduced the NSs renewing frequency. High adsorption selectivity of NSs contributed to low impurities (<0.3%) in the P-enriched reclaimed solution. Moreover, the integrated AnMBR-RO-IE-PRBR process saved 47% of energy consumption compared to the present NEWater production process in Singapore. The innovative PRBR reactor was competitive compared to the commonly-used chemical precipitation methods in conventional WWTPs in terms of phosphorus recovery/loss and energy balance. It is expected that the proposed integrated process can offer new insights into the direction of phosphorus reclamation in the future WWTPs.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131259DOI Listing
June 2021

High-Normal Serum Thyrotropin Levels Increased the Risk of Non-Alcoholic Fatty Liver Disease in Euthyroid Subjects with Type 2 Diabetes.

Diabetes Metab Syndr Obes 2021 22;14:2841-2849. Epub 2021 Jun 22.

Department of Endocrinology & Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, People's Republic of China.

Purpose: The aim of this study was to investigate the association between high-normal thyrotropin (TSH) levels and the prevalence of non-alcoholic fatty liver disease (NAFLD) in euthyroid patients with T2DM.

Methods: A total of 2289 euthyroid adults with T2DM were included in this cross-sectional study conducted at the Third Affiliated Hospital of Sun Yat-sen University from January 2016 to December 2018. NAFLD was diagnosed by abdominal ultrasound. Thyroid function parameters, including the levels of TSH, free triiodothyronine (FT3) and free thyroxine (FT4), were analyzed. The patients were stratified by quartiles (Q1-4) of TSH levels. Multivariate logistic regression models were used to evaluate the association between the quartiles of TSH levels and the risk of NAFLD in euthyroid adults with T2DM.

Results: There were 940 (41.1%) euthyroid adults with T2DM who were diagnosed with NAFLD. The subjects were divided according to the thyroid function parameter quartiles. The prevalence of NAFLD increased with increasing TSH level quartiles (Q1 to Q4: 34.8%, 37.5%, 44.9% and 47.0%, <0.01) but not with increasing FT3 or FT4 level quartiles. In the multivariate logistic regression model, compared with the lowest TSH level quartile (Q1), the highest TSH level quartile (Q4) (OR=1.610, 95% CI=1.131-2.289, =0.008) was independently associated with an increased risk of NAFLD in euthyroid adults with T2DM after adjusting for multiple confounders. After additional stratification by the level of glycosylated haemoglobin (HbA1c) and body mass index (BMI), the highest TSH level quartile was still independently associated with an increased risk of NAFLD in euthyroid patients with T2DM who had an HbA1c level≥7% or a BMI<28 kg/m.

Conclusion: High-normal serum TSH levels are significantly associated with the presence of NAFLD in T2DM patients with euthyroid function, which provide novel insight for treating NAFLD.
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http://dx.doi.org/10.2147/DMSO.S313224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235944PMC
June 2021

Effectiveness of Rehabilitation Nursing versus Usual Therapist-Led Treatment in Patients with Acute Ischemic Stroke: A Randomized Non-Inferiority Trial.

Clin Interv Aging 2021 21;16:1173-1184. Epub 2021 Jun 21.

Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People's Republic of China.

Purpose: To determine the effectiveness of rehabilitation nursing program interventions in patients with acute ischemic stroke.

Patients And Methods: An assessment-blinded randomized controlled trial was conducted at a tertiary referral hospital in China. Eligible patients were stratified according to their weighted corticospinal tract lesion load and then randomly assigned to an experimental group (n = 121) or a control group (n = 103). The experimental group received rehabilitation nursing from well-trained, qualified nurses (30 minutes per session, two sessions per day for seven consecutive days). The control group received therapist-led rehabilitation with the same timing and frequency. Comparative analysis of the primary outcomes was performed to determine non-inferiority with a predetermined non-inferiority margin. The primary outcomes were the Motor Assessment Scale, Fugl-Meyer Assessment, and the Action Research Arm Test assessed at baseline and after seven days of treatment. The secondary outcomes were the modified Barthel Index, the National Institutes of Health Stroke Scale, and the modified Rankin Scale, evaluated before and after the intervention and at 4 and 12 weeks of follow-up.

Results: Two hundred participants completed the trial. In both groups, all outcomes improved significantly after seven days and at follow-ups. The rehabilitation nursing program was non-inferior to therapist-led treatment with lower 95% confidence limits beyond the margins for primary outcomes ( < 0.001).

Conclusion: Both treatments had comparable effects; however, no definite conclusion could be drawn. Adequately powered studies are required.
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http://dx.doi.org/10.2147/CIA.S306255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233001PMC
July 2021

Effects of dexmedetomidine on behavior of and expressions of spinal cord P38 MAPK and spinal cord-related cytokines in rats with neuropathic pain.

Minerva Med 2021 Jun 28. Epub 2021 Jun 28.

Department of Anaesthesiology, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital, Taizhou, Jiangsu, China -

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http://dx.doi.org/10.23736/S0026-4806.21.07603-5DOI Listing
June 2021

An intraoral device for weight loss: initial clinical findings.

Br Dent J 2021 Jun 25. Epub 2021 Jun 25.

RMH Consultancy, Leeds, UK.

Introduction Obesity is a global epidemic, increasing the risk of many associated health issues.Aim The aim of this clinical study was to investigate the acceptability and tolerability of an intraoral device, designed to facilitate weight loss.Method Seven healthy obese participants were recruited. The device, which incorporated closed-field magnets with keepers to restrict mouth opening, was cemented to the participants' first molars. The participants were given a commercially available liquid diet for two weeks. The comfort and tolerability of the device were assessed using a quality of life questionnaire during review appointments at 1, 7 and 14 days and two weeks after device removal.Results The participants reached a mean weight loss of 6.36 (SD = 3.79) kilograms, which represents approximately 5.1% of their body weight. The participants had trouble pronouncing some words and felt tense and embarrassed 'only occasionally'. The participants 'hardly ever' reported a change in taste sensation or felt uncomfortable drinking. However, participants indicated that they occasionally had discomfort and felt that life in general was less satisfying. Qualitative analysis showed that the participants were happy with the outcome and were motivated to lose more weight.Conclusion The participants tolerated the device for a two-week period with satisfactory weight loss and were further motivated to continue their weight loss journey.
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http://dx.doi.org/10.1038/s41415-021-3081-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231740PMC
June 2021

Antitumor efficacy and reduced toxicity using an anti-CD137 Probody therapeutic.

Proc Natl Acad Sci U S A 2021 Jun;118(26)

Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Universidad de Navarra, 31008 Pamplona, Spain;

Costimulation via CD137 (4-1BB) enhances antitumor immunity mediated by cytotoxic T lymphocytes. Anti-CD137 agonist antibodies elicit mild liver inflammation in mice, and the maximum tolerated dose of Urelumab, an anti-human CD137 agonist monoclonal antibody, in the clinic was defined by liver inflammation-related side effects. A protease-activated prodrug form of the anti-mouse CD137 agonist antibody 1D8 (1D8 Probody therapeutic, Pb-Tx) was constructed and found to be selectively activated in the tumor microenvironment. This construct, which encompasses a protease-cleavable linker holding in place a peptide that masks the antigen binding site, exerted antitumor effects comparable to the unmodified antibody but did not result in liver inflammation. Moreover, it efficaciously synergized with both PD-1 blockade and adoptive T-cell therapy. Surprisingly, minimal active Pb-Tx reached tumor-draining lymph nodes, and regional lymphadenectomy did not abrogate antitumor efficacy. By contrast, S1P receptor-dependent recirculation of T cells was absolutely required for efficacy. The preferential cleavage of the anti-CD137 Pb-Tx by tumor proteases offers multiple therapeutic opportunities, including neoadjuvant therapy, as shown by experiments in which the Pb-Tx is given prior to surgery to avoid spontaneous metastases.
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http://dx.doi.org/10.1073/pnas.2025930118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255787PMC
June 2021

Transcriptome Dynamics Underlying Chlamydospore Formation in GV29-8.

Front Microbiol 2021 8;12:654855. Epub 2021 Jun 8.

Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.

spp. are widely used biocontrol agents which are antagonistic to a variety of plant pathogens. Chlamydospores are a type of propagules produced by many fungi that have thick walls and are highly resistant to adverse environmental conditions. Chlamydospore preparations of spp. can withstand various storage conditions, have a longer shelf life than conidial preparations and have better application potential. However, large-scale production of chlamydospores has proven difficult. To understand the molecular mechanisms governing chlamydospore formation (CF) in fungi, we performed a comprehensive analysis of transcriptome dynamics during CF across 8 different developmental time points, which were divided into 4 stages according to PCA analysis: the mycelium growth stage (S1), early and middle stage of CF (S2), flourishing stage of CF (S3), and late stage of CF and mycelia initial autolysis (S4). 2864, 3206, and 3630 DEGs were screened from S2 vs S1, S3 vs S2, and S4 vs S3, respectively. We then identified the pathways and genes that play important roles in each stage of CF by GO, KEGG, STC and WGCNA analysis. The results showed that DEGs in the S2 vs S1 were mainly enriched in organonitrogen compound metabolism, those in S3 vs S2 were mainly involved in secondary metabolite, cell cycle, and N-glycan biosynthesis, and DEGs in S4 vs S3 were mainly involved in lipid, glycogen, and chitin metabolic processes. We speculated that mycelial assimilation and absorption of exogenous nitrogen in the early growth stage (S1), resulted in subsequent nitrogen deficiency (S2). At the same time, secondary metabolites and active oxygen free radicals released during mycelial growth produced an adverse growth environment. The resulting nitrogen-deficient and toxin enriched medium may stimulate cell differentiation by initiating cell cycle regulation to induce morphological transformation of mycelia into chlamydospores. High expression of genes relating to glycogen, lipid, mannan, and chitin synthetic metabolic pathways during the flourishing (S3) and late stages (S4) of CF may be conducive to energy storage and cell wall construction in chlamydospores. For further verifying the functions of the amino sugar and nucleotide sugar metabolism (tre00520) pathway in the CF of GV29-8 strain, the chitin synthase gene (TRIVIDRAFT_90152), one key gene of the pathway, was deleted and resulted in the dysplasia of mycelia and an incapability to form normal chlamydospores, which illustrated the pathway affecting the CF of GV29-8 strain. Our results provide a new perspective for understanding the genetics of biochemical pathways involved in CF of spp.
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http://dx.doi.org/10.3389/fmicb.2021.654855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217873PMC
June 2021

Chemical-mediated translocation in protocell-based microactuators.

Nat Chem 2021 Jun 24. Epub 2021 Jun 24.

Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, Bristol, UK.

Artificial cell-like communities participate in diverse modes of chemical interaction but exhibit minimal interfacing with their local environment. Here we develop an interactive microsystem based on the immobilization of a population of enzyme-active semipermeable proteinosomes within a helical hydrogel filament to implement signal-induced movement. We attach large single-polynucleotide/peptide microcapsules at one or both ends of the helical protocell filament to produce free-standing soft microactuators that sense and process chemical signals to perform mechanical work. Different modes of translocation are achieved by synergistic or antagonistic enzyme reactions located within the helical connector or inside the attached microcapsule loads. Mounting the microactuators on a ratchet-like surface produces a directional push-pull movement. Our methodology opens up a route to protocell-based chemical systems capable of utilizing mechanical work and provides a step towards the engineering of soft microscale objects with increased levels of operational autonomy.
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http://dx.doi.org/10.1038/s41557-021-00728-9DOI Listing
June 2021

NADPH is superior to NADH or edaravone in ameliorating metabolic disturbance and brain injury in ischemic stroke.

Acta Pharmacol Sin 2021 Jun 24. Epub 2021 Jun 24.

Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

Our previous studies confirm that exogenous reduced nicotinamide adenine dinucleotide phosphate (NADPH) exerts a neuroprotective effect in animal models of ischemic stroke, and its primary mechanism is related to anti-oxidative stress and improved energy metabolism. However, it is unknown whether nicotinamide adenine dinucleotide (NADH) also plays a neuroprotective role and whether NADPH is superior to NADH against ischemic stroke? In this study we compared the efficacy of NADH, NADPH, and edaravone in ameliorating brain injury and metabolic stress in ischemic stroke. Transient middle cerebral artery occlusion/reperfusion (t-MCAO/R) mouse model and in vitro oxygen glucose deprivation/reoxygenation (OGD/R) model were established. The mice were intravenously administered the optimal dose of NADPH (7.5 mg/kg), NADH (22.5 mg/kg), or edaravone (3 mg/kg) immediately after reperfusion. We showed that the overall efficacy of NADPH in ameliorating ischemic injury was superior to NADH and edaravone. NADPH had a longer therapeutic time window (within 5 h) after reperfusion than NADH and edaravone (within 2 h) for ischemic stroke. In addition, NADPH and edaravone were better in alleviating the brain atrophy, while NADH and NADPH were better in increasing the long-term survival rate. NADPH showed stronger antioxidant effects than NADH and edaravone; but NADH was the best in terms of maintaining energy metabolism. Taken together, this study demonstrates that NADPH exerts better neuroprotective effects against ischemic stroke than NADH and edaravone.
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http://dx.doi.org/10.1038/s41401-021-00705-5DOI Listing
June 2021

Fabrication and characterization of zein-tea polyphenols-pectin ternary complex nanoparticles as an effective hyperoside delivery system: Formation mechanism, physicochemical stability, and in vitro release property.

Food Chem 2021 Jun 9;364:130335. Epub 2021 Jun 9.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

Hyperoside (HYP) has various potential benefits, however, its low water-solubility and poor bioavailability have restricted its application. Here, HYP-loaded zein-tea polyphenols (TP)-pectin ternary complex nanoparticles (Z/TP/P-HYP) were prepared by the antisolvent precipitation method for HYP delivery. The formed Z/TP/P-HYP are negatively charged spherical particles with a size of 246 nm, and have the highest HYP encapsulation efficiency (94.2%) at TP was 0.25 mg/mL. Fourier transform infrared spectroscopy revealed that hydrogen bonding, electrostatic interactions, and hydrophobic effects were major interactions to Z/TP/P-HYP formation. Differential scanning calorimetry confirmed that encapsulated HYP was in an amorphous state. Freeze-dried Z/TP/P-HYP displayed good water-redispersibility and high particle yield (95.2%). Z/TP/P-HYP exhibited improved pH (2.0-8.0) and ionic (0-500 mM) stability. Furthermore, Z/TP/P-HYP demonstrated stronger antioxidant properties than free HYP and provided HYP sustained release under simulated gastrointestinal conditions. Therefore, Z/TP/P-HYP have great potential as an effective HYP delivery system for applications in foods.
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http://dx.doi.org/10.1016/j.foodchem.2021.130335DOI Listing
June 2021

Health-related quality of life in men with osteoporosis: a systematic review and meta-analysis.

Endocrine 2021 Jun 24. Epub 2021 Jun 24.

Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Dongcheng District, Beijing, China.

Purpose: The increased social and economic burdens make osteoporosis in men an emerging public health issue. However, the quality of life among men with osteoporosis is still unclear. This systematic review and meta-analysis aimed to evaluate the health-related quality of life (HRQoL) among men with osteoporosis or osteoporotic fracture.

Methods: PubMed, EMBASE, and the Cochrane Library database were systematically searched from inception to May 2021. Studies were included if they used validated questionnaires to measure HRQoL among osteoporotic men. A meta-analysis was performed using a random-effects model or fixed-effects model to calculate the standard mean difference (SMD) or mean difference (MD) with 95% confidential interval (95% CI).

Results: 14 studies involving 6338 male participants were chosen for systematic review, of which 10 were included in the meta-analysis. Men with osteoporosis had poorer global HRQoL and multiple dimensions of HRQoL than men without osteoporosis. Hip fracture, vertebral fractures, or wrist fractures dramatically impaired HRQoL of men, and physical function was declined even before hip fracture (SMD = -0.60, 95% CI, -0.82 to -0.39). Femoral and lumbar BMD was positively correlated with HRQoL, and a number of fragility fractures and time since fracture had negative effects on HRQoL. Effective anti-osteoporotic drugs could improve HRQoL of men.

Conclusion: The health-related life quality of men was significantly impaired by osteoporosis and fracture of the hip, vertebral, or wrist. We should pay more attention to the diagnosis and treatment of male osteoporosis to improve the life quality of men.
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http://dx.doi.org/10.1007/s12020-021-02792-0DOI Listing
June 2021

LINC00842 inactivates transcription co-regulator PGC-1α to promote pancreatic cancer malignancy through metabolic remodelling.

Nat Commun 2021 06 22;12(1):3830. Epub 2021 Jun 22.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

The molecular mechanism underlying pancreatic ductal adenocarcinoma (PDAC) malignancy remains unclear. Here, we characterize a long intergenic non-coding RNA LINC00842 that plays a role in PDAC progression. LINC00842 expression is upregulated in PDAC and induced by high concentration of glucose via transcription factor YY1. LINC00842 binds to and prevents acetylated PGC-1α from deacetylation by deacetylase SIRT1 to form PGC-1α, an important transcription co-factor in regulating cellular metabolism. LINC00842 overexpression causes metabolic switch from mitochondrial oxidative catabolic process to fatty acid synthesis, enhancing the malignant phenotypes of PDAC cells. High LINC00842 levels are correlated with elevated acetylated- PGC-1α levels in PDAC and poor patient survival. Decreasing LINC00842 level and inhibiting fatty acid synthase activity significantly repress PDAC growth and invasiveness in mouse pancreatic xenograft or patient-derived xenograft models. These results demonstrate that LINC00842 plays a role in promoting PDAC malignancy and thus might serve as a druggable target.
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http://dx.doi.org/10.1038/s41467-021-23904-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219694PMC
June 2021
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