Publications by authors named "Qing He"

722 Publications

Identification of human uridine diphosphate-glucuronosyltransferase isoforms responsible for the glucuronidation of 10,11-dihydro-10-hydroxy-carbazepine.

J Pharm Pharmacol 2021 Mar;73(3):388-397

Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.

Objectives: To determine the kinetics of the formation of 10,11-dihydro-10-hydroxy-carbazepine (MHD)-O-glucuronide in human liver microsomes (HLMs), human intestine microsomes (HIMs), human kidney microsomes (HKMs) and recombinant human UDP-glucuronosyltransferase (UGTs), and identify the primary UGT isoforms catalyzing the glucuronidation of MHD.

Methods: The kinetics of the glucuronidation of MHD was determined in HLMs, HIMs as well as HKMs. Screening assays with 13 recombinant human UGTs, inhibition studies and correlation analysis were performed to identify the main UGTs involved in the glucuronidation of MHD.

Key Findings: MHD-O-glucuronide was formed in HLMs, HIMs as well as HKMs, HLMs showed the highest intrinsic clearance of MHD. Among 13 recombinant human UGTs, UGT2B7 and UGT1A9 were identified to be the principal UGT isoforms mediating the glucuronidation of MHD, while UGT1A4 played a partial role. In addition, inhibition studies and correlation analysis further confirmed that UGT2B7 and UGT1A9 participated in the formation of MHD-O-glucuronide.

Conclusions: MHD could be metabolized by UGTs in the liver, intestine and kidney, and the hepatic glucuronidation was the critical metabolic pathway. UGT2B7 and UGT1A9 were the primary UGT isoforms mediating the formation of MHD-O-glucuronide in the liver.
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http://dx.doi.org/10.1093/jpp/rgaa059DOI Listing
March 2021

Market-oriented job skill valuation with cooperative composition neural network.

Nat Commun 2021 03 31;12(1):1992. Epub 2021 Mar 31.

Rutgers, the State University of New Jersey, Newark, NJ, USA.

The value assessment of job skills is important for companies to select and retain the right talent. However, there are few quantitative ways available for this assessment. Therefore, we propose a data-driven solution to assess skill value from a market-oriented perspective. Specifically, we formulate the task of job skill value assessment as a Salary-Skill Value Composition Problem, where each job position is regarded as the composition of a set of required skills attached with the contextual information of jobs, and the job salary is assumed to be jointly influenced by the context-aware value of these skills. Then, we propose an enhanced neural network with cooperative structure, namely Salary-Skill Composition Network (SSCN), to separate the job skills and measure their value based on the massive job postings. Experiments show that SSCN can not only assign meaningful value to job skills, but also outperforms benchmark models for job salary prediction.
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http://dx.doi.org/10.1038/s41467-021-22215-yDOI Listing
March 2021

Ectopic insulinoma diagnosed by 68Ga-Exendin-4 PET/CT: A case report and review of literature.

Medicine (Baltimore) 2021 Apr;100(13):e25076

Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital.

Rationale: Ectopic insulinomas are extremely rare and challenging to diagnose for clinicians. Precise preoperative localization is essential to successful treatment.

Patient Concerns: A 23-year-old man presented with a 1-year history of recurrent hypoglycemia.

Diagnosis: Examinations in the local hospital did not reveal any pancreatic lesion. After admission, a fasting test and a 5-hour oral glucose tolerance test (OGTT) suggested a diagnosis of endogenous hyperinsulinemic hypoglycemia. Enhanced volume perfusion computed tomography (VPCT) revealed 2 nodules in the tail of the pancreas, a nodule in the gastric antrum, and a nodule in the hilum of the spleen. To differentiate which nodule was responsible for hypoglycemia, we performed 68Ga-Exendin-4 PET/CT and 68Ga-DOTATATE PET/CT which helped to make a conclusive diagnosis that the lesion in the gastric antrum was an ectopic insulinoma.

Interventions: The patient was cured with minimally invasive laparoscopic resection of the tumor.

Outcomes: The symptoms were relieved and the blood glucose level remained normal after surgery.

Conclusions: This case shows that 68Gallium-exendin-4 PET/CT is useful for precise localization and thereby successful treatment of insulinoma, especially for occult insulinomas and those derived from an ectopic pancreas.
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http://dx.doi.org/10.1097/MD.0000000000025076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021326PMC
April 2021

Complete genome sequence of the deep South China Sea-derived Streptomyces niveus SCSIO 3406, the producer of cytotoxic and antibacterial marfuraquinocins.

PLoS One 2021 23;16(3):e0248404. Epub 2021 Mar 23.

CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.

Streptomyces niveus SCSIO 3406 was isolated from a sediment sample collected from South China Sea at a depth of 3536 m. Four new sesquiterpenoid naphthoquinones, marfuraquinocins A-D, and two new geranylated phenazines, i. e. phenaziterpenes A and B, were isolated from the fermentation broth of the strain. Here, we present its genome sequence, which contains 7,990,492 bp with a G+C content of 70.46% and harbors 7088 protein-encoding genes. The genome sequence analysis revealed the presence of a 28,787 bp gene cluster encoding for 24 open reading frames including 1,3,6,8-tetrahydroxynaphthalene synthase and monooxygenase, seven phenazine biosynthesis proteins, two prenyltransferases and a squalene-hopene cyclase. These genes are known to be necessary for the biosynthesis of both marfuraquinocins and phenaziterpenes. Outside the gene cluster (and scattered around the genome), there are seven genes belonging to the methylerythritol phosphate pathway for the biosynthesis of the essential primary metabolite, isopentenyl diphosphate, as well as six geranyl diphosphate/farnesyl diphosphate synthase genes. The strain S. niveus SCSIO 3406 showed type I PKS, type III PKS and nonribosomal peptide synthetase cluster. The sequence will provide the genetic basis for better understanding of biosynthesis mechanism of the above mentioned six compounds and for the construction of improved strain for the industrial production of antimicrobial agents.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248404PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987185PMC
March 2021

Thallium(I) Salts: New Partners for Calix[4]pyrroles.

Org Lett 2021 Apr 18;23(7):2638-2642. Epub 2021 Mar 18.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China.

Calix[4]pyrrole can form host-guest complexes with certain thallium salts, for example, TlF, not only in the gas phase but also in solution and in the solid state. The complexation of TlF by calix[4]pyrrole was found to promote self-assembly and the formation of well-defined and highly ordered fibrous supramolecular morphologies, as revealed by polarizing microscopy and scanning electron microscopy. The findings reported here serve to broaden the scope of cationic substrates that may be complexed as ion pairs by calix[4]pyrrole receptors while setting the stage for the development of new hosts for thallium(I) salts.
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http://dx.doi.org/10.1021/acs.orglett.1c00555DOI Listing
April 2021

Comparison of F-FDG PET/CT and Ga-DOTATATE PET/CT in the Targeted Imaging of Culprit Tumors Causing Osteomalacia.

Orthop Surg 2021 Mar 11. Epub 2021 Mar 11.

Department of PET-CT Diagnostic, Tianjin Medical University General Hospital, Tianjin, China.

Objective: To assess and compare the performance of fluorine-18-labeled fluorodeoxyglucose positron emission tomography ( F-FDG-PET/ CT) and gallium-68-labeled tetraazacyclododecanetetraacetic acid-DPhe1-Tyr3-octreotate ( Ga- DOTATATE) PET/CT in the targeted imaging of culprit tumors causing osteomalacia.

Methods: This was a clinical retrospective analysis. We analyzed 13 patients (five men, eight women; mean age, 49 years; range, 19-55 years) with suspicion of tumor-induced osteomalacia (TIO) between March 2017 and October 2019. All patients underwent two functional imaging methods to locate the culprittumors. Studies were performed on a PET/CT scanner. The injection doses of F- FDG and Ga-DOTATATE were 0.5mCi/kg and approximately 5.0mCi, respectively. In the two scans, the whole body was captured from head to toe 45 to 60 min after intravenous tracer injection. Ga-DOTATATE PET/CT and F-FDG PET/CT imaging results locate culprit tumors according to the following criteria: (i) abnormal foci uptake concentration was observed locally, and the uptake level was higher than the background level of the right lobe of the liver; (ii) combined CT showed or did not have obvious abnormal density changes; and (iii) non-specific ingestion lesions due to fracture, arthritis, necrosis of femoral head are excluded. Compared with the results of pathological examination and clinical follow-up, the sensitivity, specificity and accuracy of Ga-DOTATATE PET/CT imaging and F-FDG PET/CT imaging for TIO were analyzed.

Results: All patients had symptoms of osteomalacia and hypophosphatemia. The lag time (symptoms to PET diagnosis) ranged from 2 to 12 years. There were eight cases of TIO patients and five cases of non-TIO patients confirmed by surgery, pathology and follow-up. Among the eight TIO patients, there were six cases (75.0%) of PMTs, one case (12.5%) of giant cell tumor, one case (12.5%) of hemangiopericutoma. Most (n = 6, 75.0%) of the confirmed tumors in our patient population were in the lower extremities, followed by craniofacial regions (n = 1, 12.5%), and torso (n = 1, 12.5%), respectively. Among the five non-TIO patients, there were two cases of Fanconi syndrome, one case of rickets, and two cases of sporadic osteomalacia hypophosphorus. The culprit tumors could be located either in the bone (n = 5, 62.5%) or the soft tissue (n = 3, 37.5%). F-FDG PET/CT was able to localize the tumor in six (6/13, 46.1%) patients. Ga-DOTATATE PET/CT detected tumor in 8 (83.3%) of 13 patients. The sensitivity of Ga-DOTATATE PET/CT imaging and F-FDG PET/CT imaging in the evaluation of TIO in our patient population were 100% (8/8) vs 75% (6/8). The specificity of the two different methods was 80% (4/5). The overall accuracy was 92.3% (12/13) vs 76.9% (10/13).

Conclusions: Ga-DOTATATE PET/CT is very effective in assessing hypophosphatemia patients with TIO typical symptoms compared with F-FDG. Therefore, in clinically suspected cases of hypophosphatemic osteomalacia, Ga-DOTATATE PET/CT should be preferred as an imaging modality investigation to avoid delay in the treatment of this disease.
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http://dx.doi.org/10.1111/os.12980DOI Listing
March 2021

Knowledge graph embedding with shared latent semantic units.

Neural Netw 2021 Feb 27;139:140-148. Epub 2021 Feb 27.

Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Knowledge graph embedding (KGE) aims to project both entities and relations into a continuous low-dimensional space. However, for a given knowledge graph (KG), only a small number of entities and relations occur many times, while the vast majority of entities and relations occur less frequently. This data sparsity problem has largely been ignored by most of the existing KGE models. To this end, in this paper, we propose a general technique to enable knowledge transfer among semantically similar entities or relations. Specifically, we define latent semantic units (LSUs), which are the sub-components of entity and relation embeddings. Semantically similar entities or relations are supposed to share the same LSUs, and thus knowledge can be transferred among entities or relations. Finally, extensive experiments show that the proposed technique is able to enhance existing KGE models and can provide better representations of KGs.
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http://dx.doi.org/10.1016/j.neunet.2021.02.013DOI Listing
February 2021

The NF-κB signalling pathway and TM7SF3 contribute to liver fibrosis caused by secreted phospholipase A2 of Clonorchis sinensis.

Parasit Vectors 2021 Mar 10;14(1):152. Epub 2021 Mar 10.

Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People's Republic of China.

Background: The NF-κB signalling pathway has been reported to be related to liver fibrosis, and we investigated whether the NF-κB signalling pathway is involved in liver fibrosis caused by secreted phospholipase A2 of Clonorchis sinensis (CssPLA2). Furthermore, expression of the receptor of CssPLA2 on the cell surface of hepatic stellate cells (HSCs) may greatly contribute to liver fibrosis.

Methods: CssPLA2 was administered to BALB/c mice by abdominal injection. The levels of markers of NF-κB signalling pathway activation in mouse liver tissue were measured by quantitative RT-PCR, ELISA and western blot. Additionally, HSCs were incubated with CssPLA2, and an NF-κB signalling inhibitor (BAY 11-7082) was applied to test whether the NF-κB signalling pathway plays a role in the effect of CssPLA2. Then, the interaction between CssPLA2 and its receptor transmembrane 7 superfamily member 3 (TM7SF3) was confirmed by co-immunoprecipitation (co-IP) and GST pull-down. To determine how TM7SF3 influences the ability of CssPLA2 to cause liver fibrosis, a TM7SF3 antibody was used to block TM7SF3.

Results: The levels of the NF-ΚB signalling pathway activation markers TNF-α, IL-1β and phospho-p65 were increased by CssPLA2 in the context of liver fibrosis. In addition, the interaction between TM7SF3 and CssPLA2 was confirmed by co-IP and GST pull-down. When TM7SF3 was blocked by an antibody targeting 1-295 amino acids of TM7SF3, activation of HSCs caused by CssPLA2 was alleviated.

Conclusions: The NF-ΚB signalling pathway is involved in the activation of HSCs by CssPLA2. TM7SF3, the receptor of CssPLA2, plays important roles in liver fibrosis caused by CssPLA2.
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http://dx.doi.org/10.1186/s13071-021-04663-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945307PMC
March 2021

Sampling cores and sequencing depths affected the measurement of microbial diversity in soil quadrats.

Sci Total Environ 2021 May 30;767:144966. Epub 2021 Jan 30.

Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, China.

Due to the massive quantity and broad phylogeny, an accurate measurement of microbial diversity is highly challenging in soil ecosystems. Initially, the deviation caused by sampling should be adequately considered. Here, we attempted to uncover the effect of different sampling strategies on α diversity measurement of soil prokaryotes. Four 1 m sampling quadrats in a typical grassland were thoroughly surveyed through deep 16S rRNA gene sequencing (over 11 million reads per quadrat) with numerous replicates (33 soil sampling cores with total 141 replicates per quadrat). We found the difference in diversity was relatively small when pooling soil cores before and after DNA extraction and sequencing, but they were both superior to a non-pooling strategy. Pooling a small number of soil cores (i.e., 5 or 9) combined with several technical replicates is sufficient to estimate diversities for soil prokaryotes, and there is great flexibility in pooling original samples or data at different experimental steps. Additionally, the distribution of local α diversity varies with sampling core number, sequencing depth, and abundance distribution of the community, especially for high orders of Hill diversity index (i.e., Shannon entropy and inverse Simpson index). For each grassland soil quadrat (1 m), retaining 100,000 reads after taxonomic clustering might be a realistic option, as these number of reads can efficiently cover the majority of common species in this area. Our findings provide important guidance for soil sampling strategy, and the general results can serve as a basis for further studies.
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http://dx.doi.org/10.1016/j.scitotenv.2021.144966DOI Listing
May 2021

JKAMP inhibits the osteogenic capacity of adipose-derived stem cells in diabetic osteoporosis by modulating the Wnt signaling pathway through intragenic DNA methylation.

Stem Cell Res Ther 2021 Feb 12;12(1):120. Epub 2021 Feb 12.

Department of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, 646000, China.

Background: Diabetic osteoporosis (DOP) is a systemic metabolic bone disease caused by diabetes mellitus (DM). Adipose-derived stem cells (ASCs) play an important role in bone regeneration. Our previous study confirmed that ASCs from DOP mice (DOP-ASCs) have a lower osteogenesis potential compared with control ASCs (CON-ASCs). However, the cause of this poor osteogenesis has not been elucidated. Therefore, this study investigated the underlying mechanism of the decline in the osteogenic potential of DOP-ASCs from the perspective of epigenetics and explored methods to enhance their osteogenic capacity.

Methods: The expression level of JNK1-associated membrane protein (JKAMP) and degree of DNA methylation in CON-ASCs and DOP-ASCs were measured by mRNA expression profiling and MeDIP sequencing, respectively. JKAMP small interfering RNA (siRNA) and a Jkamp overexpression plasmid were used to assess the role of JKAMP in osteogenic differentiation of CON-ASCs and DOP-ASCs. Immunofluorescence, qPCR, and western blotting were used to measure changes in expression of Wnt signaling pathway-related genes and osteogenesis-related molecules after osteogenesis induction. Alizarin red and ALP staining was used to confirm the osteogenic potential of stem cells. Bisulfite-specific PCR (BSP) was used to detect JKAMP methylation degree.

Results: Expression of JKAMP and osteogenesis-related molecules (RUNX2 and OPN) in DOP-ASCs was decreased significantly in comparison with CON-ASCs. JKAMP silencing inhibited the Wnt signaling pathway and reduced the osteogenic ability of CON-ASCs. Overexpression of JKAMP in DOP-ASCs rescued the impaired osteogenic capacity caused by DOP. Moreover, JKAMP in DOP-ASCs contained intragenic DNA hypermethylated regions related to the downregulation of JKAMP expression.

Conclusions: Intragenic DNA methylation inhibits the osteogenic ability of DOP-ASCs by suppressing expression of JKAMP and the Wnt signaling pathway. This study shows an epigenetic explanation for the reduced osteogenic ability of DOP-ASCs and provides a potential therapeutic target to prevent and treat osteoporosis.
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http://dx.doi.org/10.1186/s13287-021-02163-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881648PMC
February 2021

Temperature and microbial interactions drive the deterministic assembly processes in sediments of hot springs.

Sci Total Environ 2021 Jun 30;772:145465. Epub 2021 Jan 30.

CAS Key Laboratory for Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (CAS), Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100190, China.

Terrestrial geothermal ecosystems, as a representative of extreme environments, exhibit a variety of geochemical gradients, and their microbes are thought to be under high stress through environmental selection. However, it is still unclear how stochasticity and biotic interactions contribute to the microbial community assembly in hot springs. Here, we investigated the assembly processes and co-occurrence patterns of microbiota (i.e. bacteria and archaea) in both water and sediments sampled from fifteen hot springs in the Tengchong area, Southwestern of China, using 16S rRNA gene sequencing combined with multivariate ecological and statistical methods. These hot springs harbored more specialists than non-geothermal ecosystems, which are well-adapted to the extreme conditions, as shown by extremely high nearest-taxon index (NTI) and narrower niche width. Habitat differentiation led to the differences in microbial diversity, species-interactions, and community assembly between water and sediment communities. The sediment community showed stronger phylogenetic clustering and was primarily governed by heterogeneous selection, while undominated stochastic processes and dispersal limitation were the major assembly processes in the water community. Temperature and ferrous iron were the major factors mediating the balance of stochastic and deterministic assembly processes in sediment communities, as evidenced by how divergences in temperature and ferrous iron increased the proportion of determinism. Microbial interactions in sediments contributed to deterministic community assembly, as indicated by more complex associations and greater responsiveness to environmental change than water community. These findings uncover the ecological processes underlying microbial communities in hot springs, and provide potential insight into understanding the mechanism to maintain microbial diversity in extreme biospheres.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145465DOI Listing
June 2021

Changes in precipitation amounts and extremes across Xinjiang (northwest China) and their connection to climate indices.

PeerJ 2021 25;9:e10792. Epub 2021 Jan 25.

Institute of Desert Meteorology, China Meteorological Administration, Urumqi, China.

Xinjiang is a major part of China's arid region and its water resource is extremely scarcity. The change in precipitation amounts and extremes is of significant importance for the reliable management of regional water resources in this region. Thus, this study explored the spatiotemporal changes in extreme precipitation using the Mann-Kendall (M-K) trend analysis, mutation test, and probability distribution functions, based on the observed daily precipitation data from 89 weather stations in Xinjiang, China during 1961-2018. We also examined the correlations between extreme precipitation and climate indices using the cross-wavelet analysis. The results indicated that the climate in Xinjiang is becoming wetter and the intensity and frequency of extreme precipitation has begun to strengthen, with these trends being more obvious after the 1990s. Extreme precipitation trends displayed spatial heterogeneity in Xinjiang. Extreme precipitation was mainly concentrated in mountainous areas, northern Xinjiang, and western Xinjiang. The significant increasing trend of extreme precipitation was also concentrated in the Tianshan Mountains and in northern Xinjiang. In addition, the climate indices, North Atlantic Oscillation, Atlantic Multidecadal Oscillation, Multivariate ENSO Index and Indian Ocean Dipole Index had obvious relationships with extreme precipitation in Xinjiang. The relationships between the extreme precipitation and climate indices were not clearly positive or negative, with many correlations advanced or delayed in phase. At the same time, extreme precipitation displayed periodic changes, with a frequency of approximately 1-3 or 4-7 years. These periodic changes were more obvious after the 1990s; however, the exact mechanisms involved in this require further study.
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http://dx.doi.org/10.7717/peerj.10792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842144PMC
January 2021

Association between Physical Activity and Fundamental Movement Skills in Preschool-Aged Children: Does Perceived Movement Skill Competence Mediate This Relationship?

Int J Environ Res Public Health 2021 02 1;18(3). Epub 2021 Feb 1.

Department of Sports Science and Physical Education, Faculty of Education, The Chinese University of Hong Kong, Hong Kong 999077, China.

Objectives: The purpose of this research is to examine whether perceived fundamental movement skills (FMS) competence mediated the relationship between actual FMS and physical activity (PA) in Hong Kong preschool-aged children.

Design: A cross-sectional study.

Methods: 148 preschool-aged children (43% girls; mean age = 4.52 ± 0.67 years) from five preschools/childcare centres completed all assessments. Actual FMS was rated using the Test of Gross Motor Development-2, whilst perceived FMS was assessed via the Pictorial Scale for Perceived Movement Skill Competence. PA was measured through accelerometry. A bootstrap method was used to assess the potential mediating effect of perceived movement skill competence on the relationship between actual FMS and PA. All mediation models were adjusted for sex and age.

Results: Mediation analyses showed that the direct path between actual FMS and moderate-to-vigorous physical activity (MVPA) was significant (b = 0.228, = 0.008), as was the path between MVPA and actual FMS (b = 0.214, = 0.008). However, perceived FMS competence did not mediate the association between actual FMS and MVPA in the models.

Conclusions: Our results showed evidence of reciprocal pathways between actual FMS and MVPA, reinforcing the need to simultaneously target both domains as part of broader developmental strategies, initiated in early childhood. Unlike emergent adolescence, perceptions of movement skill competence do not play a significant role in influencing the relationship between actual FMS proficiency and MVPA in this developmental period.
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http://dx.doi.org/10.3390/ijerph18031289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908079PMC
February 2021

Offline transcranial direct current stimulation improves the ability to perceive crowded targets.

J Vis 2021 Feb;21(2)

School of Psychological and Cognitive Sciences and Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, People's Republic of China.

The deleterious effect of nearby flankers on target identification in the periphery is known as visual crowding. Studying visual crowding can advance our understanding of the mechanisms of visual awareness and object recognition. Alleviating visual crowding is one of the major ways to improve peripheral vision. The aim of the current study was to examine whether transcranial direct current stimulation (tDCS) was capable of alleviating visual crowding at different visual eccentricities and with different visual tasks. In the present single-blind sham-controlled study, subjects were instructed to perform an orientation discrimination task or a letter identification task with isolated and crowded targets in the periphery, before and after applying 20 minutes of 2 mA anodal tDCS to visual cortex of the hemisphere contralateral or ipsilateral to visual stimuli. Contralateral tDCS significantly alleviated the orientation crowding effect at two different eccentricities and the letter crowding effect. This alleviation was absent after sham or ipsilateral stimulation and could not be fully explained by the performance improvement with the isolated targets. These findings demonstrated that offline tDCS was effective in alleviating visual crowding across different visual eccentricities and tasks, therefore providing a promising way to improve spatial vision rapidly in crowded scenes.
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http://dx.doi.org/10.1167/jov.21.2.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862736PMC
February 2021

Cardiac Shock Wave Therapy Alleviates Hypoxia/Reoxygenation-Induced Myocardial Necroptosis by Modulating Autophagy.

Biomed Res Int 2021 19;2021:8880179. Epub 2021 Jan 19.

Department of Cardiology, Beijing Hospital, Beijing 100730, China.

Regulated necrosis (necroptosis) is crucially involved in cardiac ischaemia-reperfusion injury (MIRI). The aim of our study is to investigate whether shock wave therapy (SWT) is capable of exerting protective effects by inhibiting necroptosis during myocardial ischaemia-reperfusion (I/R) injury and the possible role of autophagy in this process. We established a hypoxia/reoxygenation (H/R) model using HL-1 cells to simulate MIRI. MTS assays and LDH cytotoxicity assay were performed to measure cell viability and cell damage. Annexin V/PI staining was used to determine apoptosis and necrosis. Western blotting was performed to assess the changes in cell signaling pathways associated with autophagy, necroptosis, and apoptosis. Reactive oxygen species (ROS) production was detected using DHE staining. Autophagosome generation and degradation (autophagic flux) were analysed using GFP and RFP tandemly tagged LC3 (tfLC3). HL-1 cells were then transfected with p62/SQSTM1 siRNA in order to analyse its role in cardioprotection. Our results revealed that SWT increased cell viability in the H/R model and decreased receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3 expression. ROS production was also inhibited by SWT. Moreover, SWT decreased Beclin1 expression and the ratio of LC3-II/LC3-I following H/R. Simultaneously, in the tfLC3 assay, the SWT provoked a decrease in the cumulative autophagosome abundance. siRNA-mediated knockdown of p62 attenuated H/R-induced necroptosis, and SWT did not exert additive effects. Taken together, SWT ameliorated H/R injury by inhibiting necroptosis. SWT also relieved the blockade of autophagic flux in response to H/R injury. The restoration of autophagic flux by SWT might contribute to its cardioprotective effect on necroptosis following H/R injury.
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http://dx.doi.org/10.1155/2021/8880179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837773PMC
January 2021

Assessment of a novel oleaginous filamentous microalga Klebsormidium sp. Lgx80 (Streptophyta, Klebsormidiales) for biomass and lipid production.

J Phycol 2021 Feb 2. Epub 2021 Feb 2.

SDIC Microalgae Biotechnology Center, SDIC Biotech Investment Co. LTD, Beijing, 100000, China.

Commercial cultivation of eukaryotic microalgae has so far employed a unicellular form of species only (e.g., Chlorella pyrenoidosa, Dunaliella salina and Haematococcus pluvialis). In this study, we assessed the feasibility of using the filamentous eukaryotic microalga Klebsormidium sp. LGX80 as a new cultivar for biomass and lipid production. The effects of different forms and concentrations of nitrogen on growth and lipid production of Klebsormidium sp. LGX80 were studied by using a glass column (ø4.5×60 cm) photobioreactor under laboratory conditions. Growth and lipid production of the new strain were further evaluated in a pilot-scale tubular photobioreactor outdoors. The results showed that when supplied with urea as a source of nitrogen Klebsormidium sp. LGX80 yielded a final biomass concentration of 8.49±0.10 g · L in which a cellular lipid content of was 59.2±0.4% DW. Under such conditions, the biomass and lipid productivities were 471.7±5.9 and 248.1±0.0 mg · L · d , respectively. Fatty acid analysis revealed that the main fatty acids of Klebsormidium sp. LGX80 were palmitic acid (C16:0), linoleic acid (C18:2ω6) and linolenic acid (C18:3ω3), of which linoleic acid (C18:2ω6) accounted for up to 67.5±0.1% of total fatty acids. When grown in a 13,000 liter tubular photobioreactor outdoors with an initial nitrogen concentration of 3 mM urea, Klebsormidium sp. LGX80 reached the highest biomass concentration of 2.63±0.09 g · L with the cells containing 38.0±0.5% lipids (% DW), resulting in the volumetric biomass and lipid productivities of 147.2±3.6 and 37.9±0.9 mg · L d respectively. The results of light:dark cycle experiment showed that a durative and prolonged light irradiation hindered the biosynthesis of chlorophyll a and chlorophyll b in the cells, but promoted the carotenoid accumulation. These results suggested that Klebsormidium sp. LGX80 can be a potential oleaginous filamentous microalga for commercial production of microalgal oils.
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http://dx.doi.org/10.1111/jpy.13137DOI Listing
February 2021

Analyzing Risk of Service Failures in Heavy Haul Rail Lines: A Hybrid Approach for Imbalanced Data.

Risk Anal 2021 Jan 27. Epub 2021 Jan 27.

Department of Industrial and Systems Engineering, University at Buffalo, the State University of New York, Buffalo, NY, USA.

An incident in which a rail defect of size over a threshold value is noticed and the track is taken out of service is known as a service failure. This article aims at building accurate prediction models with binary outcome for risk of service failures on heavy haul rail segments. An analysis of the factors that influence the risk of a service failure is conducted and quantitative models are developed to predict locations where service failures are most likely to occur until the next inspection. To this end, data are collected from a Class I U.S. Railroads for six years from 2011 to 2016. Four prediction models (i.e., logistic regression, decision tree, multilayer perceptron, and gradient boosting classifier) are implemented and their results are compared. To account for the imbalanced classes between the normal operation and service failure, two treatments have been used including undersampling and oversampling. To improve the model performance, the parameters of each method are tuned using random search hyperparameter optimization. Later, bootstrap aggregation (or bagging) is incorporated into each method. The findings of the study show that the prediction performance is the highest when using bagging and oversampling as treatments with gradient boosting method. It was also identified that gross tonnage, presence of geometry defects, ambient temperature, segment length, and rail defect presence are the most important factors for predicting the risk of service failures. The results of this study are useful for railroads to develop effective strategies for rail inspections, preventive maintenance, and capital planning.
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http://dx.doi.org/10.1111/risa.13694DOI Listing
January 2021

Aerosol optical depth (AOD): spatial and temporal variations and association with meteorological covariates in Taklimakan desert, China.

PeerJ 2021 5;9:e10542. Epub 2021 Jan 5.

College of Resources and Environment Sciences, Xinjiang University, Urumqi, China.

Aerosol optical depth (AOD) is a key parameter that reflects aerosol characteristics. However, research on the AOD of dust aerosols and various environmental variables is scarce. Therefore, we conducted in-depth studies on the distributions and variations of AOD in the Taklimakan Desert and its margins, China. We examined the correlation characteristics between AOD and meteorological factors combined with satellite remote sensing detection methods using MCD19A2-MODIS AOD products (from 2000, 2005, 2010, and 2015), MOD13Q1-MODIS normalized difference vegetation index products, and meteorological data. We analyzed the temporal and spatial distributions of AOD, periodic change trends, and important impacts of meteorological factors on AOD in the Taklimakan Desert and its margins. To explore the relationships between desert aerosols and meteorological factors, a random forest model was used along with environmental variables to predict AOD and rank factor contributions. Results indicated that the monthly average AOD exhibited a clear unimodal curve that reached its maximum in April. The AOD values followed the order spring (0.28) > summer (0.27) > autumn (0.18) > winter (0.17). This seasonality is clear and can be related to the frequent sandstorms occurring in spring and early summer. Interannual AOD showed a gradually increasing trend to 2010 then large changes to 2015. AOD tends to increase from south to north. Based on the general trend, the maximum value of AOD is more dispersed and its low-value area is always stable. The climatic index that has the most significant effect on AOD is relative humidity.
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http://dx.doi.org/10.7717/peerj.10542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792517PMC
January 2021

Development and validation of a novel index for the differential diagnosis of corticotropin-dependent Cushing syndrome.

Pituitary 2021 Jan 27. Epub 2021 Jan 27.

Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, No. 154, Anshan, Road, Heping District, Tianjin, 300052, China.

Purpose: To develop an index for the differential diagnosis of corticotropin-dependent Cushing syndrome (CS).

Methods: The development cohort included 112 consecutive patients with clinicopathologically confirmed corticotropin-dependent CS at the Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, from December 2004 to May 2020, and data of 126 patients from studies published from 2016 to August 2020, identified through search in PubMed, Embase and the Cochrane Library, was extracted for external validation. The index was calculated as the product of plasma adrenocorticotropic hormone (ACTH, pmol/L) and urinary free cortisol (UFC, nmol/24 h) divided by 10,000. The discriminative ability was tested using receiver operating characteristics (ROC) curve analysis.

Results: In development cohort, area under curve of ROC analysis of the ACTH-UFC index in identifying Cushing disease (CD) was 0.977. The diagnostic accuracy of ACTH-UFC index ≤ 11 was comparable to that of 48 h 8 mg/d high-dose dexamethasone test (HDDST) in identifying CD, with sensitivity, specificity, positive and negative likelihood ratios of 96.6%, 87.5%, 7.73, and 0.04, respectively. The sensitivity of ACTH-UFC index ≤ 11 in parallel combination with pituitary magnetic resonance imaging (MRI) was 100% for identifying CD. The performance of the ACTH-UFC index in parallel or serial combination with pituitary MRI was similar in the validation cohort.

Conclusions: ACTH-UFC index provides a rapid, convenient and non-invasive adjunctive approach for the differential diagnosis of corticotropin-dependent CS, with no risk of aggravating metabolic disturbances. Investigations for ectopic causes of corticotropin-dependent CS should be performed with ACTH-UFC index > 11 and negative contrasted pituitary MRI.
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http://dx.doi.org/10.1007/s11102-021-01126-7DOI Listing
January 2021

Analysis of Coal Gasification Reactivity, Kinetics, and Mechanism with Iron-Based Catalyst from Coal Liquefaction.

ACS Omega 2021 Jan 6;6(2):1584-1592. Epub 2021 Jan 6.

Institute of Clean Coal Technology, East China University of Science and Technology, Shanghai 200237, P. R. China.

In this work, the effect of an iron-based catalyst from coal liquefaction on coal gasification was studied. Two catalyst loading methods and three catalyst loading contents were taken into consideration. Besides, the carbon structure, surface morphology, and element distribution of coal char and gasified semi-char were investigated, and the interactions between the catalyst and internal minerals of coal were studied. The results showed that the coal char prepared by wet impregnation had higher reactivity than that prepared by a dry mixing method. From the perspective of improving the coal reactivity, the optimal addition method should be wet impregnation with a 2% catalyst. The model-free and model-fitting methods were applied to study the catalytic gasification kinetics. The iron-based catalyst would be broken during wet impregnation, and the catalyst fragments could stick to the surface of coal char, resulting in higher reactivity. The graphitization of char increased with the addition of the iron-based catalyst. This can imply that the carbon structure cannot effectively represent the gasification reactivity in the presence of the iron-based catalyst. The Iron-based catalyst can accelerate the gasification rate alone and can also provide higher catalytic activity with the internal minerals of coal.
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http://dx.doi.org/10.1021/acsomega.0c05425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818629PMC
January 2021

Comparison of Clinical Characteristics and Outcomes of Pediatric and Adult Patients with Coronavirus Disease 2019 in Shenzhen, China.

Biomed Environ Sci 2020 Dec;33(12):906-915

National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Department of Hepatology, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, Guangdong, China.

Objective: Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19.

Methods: A total of 333 consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated in the departments of Internal medicine of Shenzhen Third People's Hospital from January 11 to February 10 , 2020 were included. The data were obtained from electronic medical records. The epidemiological data, clinical characteristics, length of hospital stays, and outcomes of pediatric and adult patients were compared.

Results: Compared with adult patients, pediatric patients had a shorter time of symptom onset to hospitalization than adults [median time, 1 ( , 1.0-1.0) d 3 ( , 2.0-6.0) d, < 0.001], milder or fewer symptoms, less severe chest CT findings. The clinical severity classification of children was less severe than adults. Up to 15 March, the end of the follow-up, 33 (100%) children and 292 (97.3%) adult patients had been discharged from hospital. Only 2 (0.7%) adult patients died, with an overall case mortality of 0.6%. The median length of hospital stay of pediatric patients was shorter than that of adult patients [19 (95% : 16.6-21.4) d 21 (95% : 19.9-22.1) d, = 0.024].

Conclusion: Pediatric patients with COVID-19 had milder or less clinical symptoms, less evident pulmonary imaging changes, better prognosis, and shorter length of hospital stay.
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http://dx.doi.org/10.3967/bes2020.124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817450PMC
December 2020

ERECTA signaling regulates plant immune responses via chromatin-mediated promotion of WRKY33 binding to target genes.

New Phytol 2021 04 18;230(2):737-756. Epub 2021 Feb 18.

College of Life Sciences, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Key Laboratory of Genetics, Breeding and Multiple Utilization of Crops, Ministry of Education, State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

The signaling pathway mediated by the receptor-like kinase ERECTA (ER) plays important roles in plant immune responses, but the underlying mechanism is unclear. Genetic interactions between ER signaling and the chromatin remodeling complex SWR1 in the control of plant immune responses were studied. Electrophoretic mobility shift assay and yeast one-hybrid analysis were applied to identify ER-WRKY33 downstream components. Chromatin immunoprecipitation analyses were further investigated. In this study, we show that the chromatin remodeling complex SWR1 enhances resistance to the white mold fungus Sclerotinia sclerotiorum in Arabidopsis thaliana via a process mediated by ER signaling. We identify a series of WRKY33 target YODA DOWNSTREAM (YDD) genes and demonstrate that SWR1 and ER signaling are required to enrich H2A.Z histone variant and H3K4me3 histone modification at YDDs and the binding of WRKY33 to YDD promoters upon S. sclerotiorum infection. We also reveal that the binding of WRKY33 to YDD promoters in turn promotes the enrichment of H2A.Z and H3K4me3 at YDD genes, thereby forming a positive regulatory loop to activate YDDs expression. Our study reveals how H2A.Z, H3K4me3 and ER signaling mutually regulate YDDs gene expression upon pathogen infection, highlighting the critical role of chromatin structure in ER-signaling-mediated plant immune responses.
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http://dx.doi.org/10.1111/nph.17200DOI Listing
April 2021

CD133 peptide-conjugated pyropheophorbide-a as a novel photosensitizer for targeted photodynamic therapy in colorectal cancer stem cells.

Biomater Sci 2021 Mar 13;9(6):2020-2031. Epub 2021 Jan 13.

Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

Colorectal cancer (CRC) is the third most common cancer around the world. Recent findings suggest that cancer stem cells (CSCs) play a pivotal role in the resistance to current therapeutic modalities, including surgery and chemotherapy. Photodynamic therapy (PDT) is a promising non-invasive therapeutic strategy for advanced metastatic CRC. Traditional photosensitizers such as pyropheophorbide-a (Pyro) lack tumor selectivity, causing unwanted treatment-related toxicity to the surrounding normal tissue. In order to enhance the targeting properties of Pyro, we synthesize a novel photosensitizer, CD133-Pyro, via the conjugation of Pyro to a peptide domain targeting CD133, which is highly expressed on CRC CSCs and correlated with poor prognosis of CRC patients. We demonstrate that CD133-Pyro possesses the targeted delivery capacity both in CRC CSCs derived from HT29 and SW620 cell lines and in a xenograft mouse model of tumor growth. CD133-Pyro PDT can promote the production of reactive oxygen species (ROS), suppress the stemness properties, and induce autophagic cell death in CRC CSCs. Furthermore, CD133-Pyro PDT has a potent inhibitory effect on CRC CSC-derived xenograft tumors in nude mice. These findings may offer a useful and important strategy for the treatment of CRC through targeting CSCs.
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http://dx.doi.org/10.1039/d0bm01874kDOI Listing
March 2021

Cognitive Gains of Aerobic Exercise in Patients With Ischemic Cerebrovascular Disorder: A Systematic Review and Meta-Analysis.

Front Cell Dev Biol 2020 18;8:582380. Epub 2020 Dec 18.

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

Cognitive impairment has become an important problem in ischemic cerebrovascular disorder survivors as disease related deaths have been significantly reduced. Aerobic exercise, the most prevalent mode of physical activity, positively contributes to cognition in both healthy population and people with cognitive impairment. However, studies on its associations with cognitive gains in patients with ischemic cerebrovascular disease showed mixed findings. To explore the cognitive effects of aerobic exercise on ischemic cerebrovascular disorder survivors and investigate the possible moderators on exercise benefits. Randomized controlled trials investigating the effects of sole aerobic exercise on cognitive function in population with ischemic intracranial vascular disorder compared to any control group who did not receive the intervention were enrolled in this systematic review and meta-analysis. Four online database (Pubmed, Cochrane Library, Embase, and Web of Science) were searched. The initial search returned 1,522 citations and ultimately 11 studies were included in the systematic review. Analysis of seven studies showed the beneficial but not statistically significant impact of aerobic exercise on global cognitive function (0.13; 95% Cl -0.09 to 0.35; = 0.25). Participants already with cognitive impairment benefited more from this intervention (0.31; 95% Cl 0.07-0.55; = 0.01) and moderate intensity might be the optimal choice (0.34; 95% Cl -0.01 to 0.69; = 0.06). The program duration and initiation time after stroke occurrence did not predict better cognitive outcome. Aerobic exercise was not associated with improvement of processing speed and executive function, the two subdomains of cognitive function. Aerobic exercise may contribute to cognitive gains in survivors of ischemic cerebrovascular disorder, especially for population already with cognitive decline. Our findings suggest that the adoption of moderate intensity aerobic exercise might improve cognition in such population.
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http://dx.doi.org/10.3389/fcell.2020.582380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775417PMC
December 2020

Broadband Visible Nonlinear Absorption and Ultrafast Dynamics of the TiC Nanosheet.

Nanomaterials (Basel) 2020 Dec 17;10(12). Epub 2020 Dec 17.

Electronic Engineering College, Heilongjiang University, Harbin 150080, China.

The TiC nanosheet, as a new two-dimensional (2D) group, has been found to have attractive characteristics as material for electromagnetic shielding and energy storage. In this study, the nonlinear broadband absorption and ultrafast dynamics of the TiC nanosheet were investigated using nanosecond open-aperture Z-scan and transient absorption techniques. The mechanism of two-photon absorption (TPA) was revealed in the visible region (475-700 nm). At lower incident energies, nonlinear absorption could not happen. When the laser energy increased to 0.64 GW/cm, electrons in the valence band could absorb two photons and jump to the conduction band, with TPA occurring, which meant that the sample exhibited reverse saturable absorption (RSA). In addition, when transient absorption was used to investigate the ultrafast carrier dynamics of the sample, it demonstrated that the relaxation contains a fast decay component and a slow one, which are obtained from electron-phonon and phonon-phonon interactions, respectively. Moreover, with the increasing pump fluence, the fast decay lifetime τ increased from 3.9 to 4.5 ps, and the slow one τ increased from 11.1 to 13.2 ps. These results show that the TiC nanosheet has potential applications in broadband optical limiters.
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http://dx.doi.org/10.3390/nano10122544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767056PMC
December 2020

Acarbose bioequivalence: Exploration of eligible protocol design.

J Clin Pharm Ther 2021 Apr 16;46(2):492-503. Epub 2020 Dec 16.

Drug Clinical Trial Institution, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi Jiangsu, China.

What Is Known And Objective: Acarbose is a poorly absorbed α-glucosidase inhibitor that acts locally in the intestinal tract. Therefore, the evaluation of its bioequivalence (BE) should be based on pharmacodynamic (PD) rather than pharmacokinetic (PK) endpoints. Currently, there is no consensus on the best method for acarbose BE evaluation. The optimal protocol design regarding dosing time/dose and PD parameters requires further exploration. The aim of the study was to identify an optimum protocol for establishing acarbose BE in healthy Chinese volunteers using PD endpoints.

Methods: Three pilot studies were conducted in healthy Chinese subjects. Study 1 was an open, randomized, two-period crossover study using the reference (R) drug at the dose of 1 × 50 mg. Study 1 aimed to determine appropriate dosing time by comparing the PD effect of acarbose between two administration methods. One method was concomitant administration of sucrose and acarbose, and another method was acarbose administration 10 min before sucrose. Study 2 was an open, randomized, three-period crossover study. Subjects were given the R drug at the dose of 1 × 50 mg, 2 × 50 mg or 3 × 50 mg in a random sequence. The aim of Study 2 was to identify a reasonable dose of acarbose in the BE study. Study 3 was conducted with an open, randomized, three-period crossover design using the test (T) or R drug in an R-T-R sequence at the dose of 2 × 50 mg. Study 3 aimed to compare the BE between the R and T drug and determine intra-individual variation. Twelve subjects were recruited in Study 1, Study 2 and Study 3, respectively, with a one-week washout period. Serum glucose and insulin concentrations were determined after sucrose administration (baseline) and sucrose/acarbose co-administration.

Results And Discussion: In Study 1, no significant differences in PD parameters were found between the two administration methods. The results of Study 2 revealed that the optimal dose was between 1 × 50 mg and 2 × 50 mg. The comparison of PD parameters indicated that the rectifying method could distinguish between different formulations. Study 3 showed that the geometric mean ratios of C , AUC and AUC were 90.06%, 84.55% and 84.21%, respectively, using the rectifying method. The 90% CIs of C were within acceptance limits (80.00%-125.00%), whereas that of AUC and AUC were out of the range. The intra-individual variation was approximately 21% for R formulation. Based on the variation, the number of subjects needed to identify formulation differences in the pivotal study would be 55 with 90% power at the 5% level of significance.

What Is New And Conclusion: The results from our study manifested that a randomized, balanced, two-way crossover design was eligible to evaluate acarbose BE. The appropriate dosing time was concomitant administration of sucrose and acarbose, and the optimal dose was 2 × 50 mg. The rectifying method exhibited preferable sensitivity and applicability in acarbose BE evaluation. A practical sample size of the pivotal study would be 55. These results may help to provide new insights into the protocol design of acarbose BE study.
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http://dx.doi.org/10.1111/jcpt.13313DOI Listing
April 2021

Steeper spatial scaling patterns of subsoil microbiota are shaped by deterministic assembly process.

Mol Ecol 2021 02 26;30(4):1072-1085. Epub 2020 Dec 26.

CAS Key Laboratory for Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (CAS), Beijing, China.

Although many studies have investigated the spatial scaling of microbial communities living in surface soils, very little is known about the patterns within deeper strata, nor is the mechanism behind them. Here, we systematically assessed spatial scaling of prokaryotic biodiversity within three different strata (Upper: 0-20 cm, Middle: 20-40 cm, and Substratum: 40-100 cm) in a typical grassland by examining both distance-decay (DDRs) and species-area relationships (SARs), taxonomically and phylogenetically, as well as community assembly processes. Each layer exhibited significant biogeographic patterns in both DDR and SAR (p < .05), with taxonomic turnover rates higher than phylogenetic ones. Specifically, the spatial turnover rates, β and z values, respectively, ranged from 0.016 ± 0.005 to 0.023 ± 0.005 and 0.065 ± 0.002 to 0.077 ± 0.004 across soil strata, and both increased with depth. Moreover, the prokaryotic community in grassland soils assembled mainly according to deterministic rather than stochastic mechanisms. By using normalized stochasticity ratio (NST) based on null model, the relative importance of deterministic ratios increased from 48.0 to 63.3% from Upper to Substratum, meanwhile a phylogenetic based method revealed average βNTI also increased with depth, from -5.29 to 19.5. Using variation partitioning and distance approaches, both geographic distance and soil properties were found to strongly affect biodiversity structure, the proportions increasing with depth, but spatial distance was always the main underlying factor. These indicated increasingly deterministic proportions in accelerating turnover rates for spatial assembly of prokaryotic biodiversity. Our study provided new insights on biogeography in different strata, revealing importance of assembly patterns and mechanisms of prokaryote communities in below-surface soils.
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http://dx.doi.org/10.1111/mec.15777DOI Listing
February 2021

Adipocytes promote breast tumorigenesis through TAZ-dependent secretion of Resistin.

Proc Natl Acad Sci U S A 2020 12 14;117(52):33295-33304. Epub 2020 Dec 14.

The Brain Science Center, Beijing Institute of Basic Medical Sciences, 100850 Beijing, China;

Adipocytes have been implicated in breast tumor growth and stemness maintenance through secreted factors. However, the mechanisms by which these cytokines are regulated during diet-induced obesity and contribute to breast tumorigenesis remain largely unknown. Here we show that transcription cofactor TAZ in adipocytes is directly up-regulated by the free fatty acid/PPARγ axis upon dietary fat stimulation. TAZ knockdown alters the expression profile of a series of secreted proteins and attenuates the tumor-supporting function of adipocytes. Moreover, we identify Resistin, an adipose-derived hormone, as a functional downstream target of TAZ, which facilitates tumorigenesis, and its expression correlated with adipocyitc TAZ in triple-negative breast cancer samples. Further, Adiponectin-cre-mediated TAZ knockout in adipocytes mitigates breast tumor growth. Taken together, our findings highlight how diet-induced TAZ expression in adipocytes promotes tumorigenesis, suggesting promising cancer therapeutic targets.
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http://dx.doi.org/10.1073/pnas.2005950117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776784PMC
December 2020

Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility.

Cell Discov 2020 Nov 10;6(1):83. Epub 2020 Nov 10.

The Third People's Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518112, China.

The COVID-19 pandemic has accounted for millions of infections and hundreds of thousand deaths worldwide in a short-time period. The patients demonstrate a great diversity in clinical and laboratory manifestations and disease severity. Nonetheless, little is known about the host genetic contribution to the observed interindividual phenotypic variability. Here, we report the first host genetic study in the Chinese population by deeply sequencing and analyzing 332 COVID-19 patients categorized by varying levels of severity from the Shenzhen Third People's Hospital. Upon a total of 22.2 million genetic variants, we conducted both single-variant and gene-based association tests among five severity groups including asymptomatic, mild, moderate, severe, and critical ill patients after the correction of potential confounding factors. Pedigree analysis suggested a potential monogenic effect of loss of function variants in GOLGA3 and DPP7 for critically ill and asymptomatic disease demonstration. Genome-wide association study suggests the most significant gene locus associated with severity were located in TMEM189-UBE2V1 that involved in the IL-1 signaling pathway. The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population. We identified that the HLA-A*11:01, B*51:01, and C*14:02 alleles significantly predispose the worst outcome of the patients. This initial genomic study of Chinese patients provides genetic insights into the phenotypic difference among the COVID-19 patient groups and highlighted genes and variants that may help guide targeted efforts in containing the outbreak. Limitations and advantages of the study were also reviewed to guide future international efforts on elucidating the genetic architecture of host-pathogen interaction for COVID-19 and other infectious and complex diseases.
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http://dx.doi.org/10.1038/s41421-020-00231-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653987PMC
November 2020