Publications by authors named "Hui Tang"

649 Publications

Using CRISPR/Cas9 for Large Fragment Deletions in .

Bio Protoc 2017 Jul 20;7(14):e2415. Epub 2017 Jul 20.

Key Laboratory of Microbial Diversity Research and Application of Hebei Province, Key discipline of biological engineering of Hebei province, College of Life Sciences, Hebei University, Baoding, China.

CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) systems have emerged as a powerful tool for genome editing in many organisms. The wide use of CRISPR/Cas9 systems may be due to the fact that these systems contain a simple guide RNA (sgRNA) that is relatively easy to design and they are very versatile with the ability to simultaneously target multiple genes within a cell ( Varshney , 2015 ). We have developed a CRISPR/Cas9 system to delete large genomic fragments (exceeding 30 kb) in One application of this technology is to study the effects of large-scale deletions of non-essential genes which may give insight into the function of gene clusters within chromosomes at the molecular level. In this protocol, we describe the general procedures for large fragment deletion in using CRISPR/Cas9 including: how to design CRISPR arrays and how to construct Cas9-crRNA expression plasmids as well as how to detect mutations introduced by the system within cells.
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http://dx.doi.org/10.21769/BioProtoc.2415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413573PMC
July 2017

Superimposition of metabolic syndrome magnifies post-stenotic kidney injury in dyslipidemic pigs.

Am J Transl Res 2021 15;13(8):8965-8976. Epub 2021 Aug 15.

Division of Nephrology and Hypertension, Mayo Clinic Rochester, MN 55905, The United States.

Background: Dyslipidemia aggravates kidney injury distal to atherosclerotic renal artery stenosis (ARAS). Besides dyslipidemia, metabolic syndrome (MetS) also involves development of obesity and insulin-resistance (IR). We hypothesized that concurrent obesity and IR magnify swine stenotic-kidney damage beyond dyslipidemia.

Methods: Pigs with unilateral RAS were studied after 16 weeks of atherogenic diets without (ARAS) or with (MetS + RAS) development of obesity/IR (n=6 each). Additional pigs on normal diet served as normal or non-dyslipidemic RAS controls (n=6 each). Stenotic-kidney renal blood flow (RBF), glomerular filtration rate (GFR), and microvascular architecture were studied using CT, and oxygenation was studied using blood oxygen level-dependent magnetic-resonance-imaging. We further compared kidney adiposity, oxidative stress, inflammation, apoptosis, fibrosis, and systemic levels of oxidative and inflammatory cytokines.

Results: ARAS and MetS + RAS developed hypertension and dyslipidemia, and MetS + RAS also developed obesity and IR. RBF and GFR were similarly decreased in all post-stenotic pig kidneys compared to normal pig kidneys, yet MetS + RAS aggravated and expanded medullary hypoxia and microvascular loss. RAS and ARAS increased systemic levels of tumor necrosis factor (TNF)-α, which were further elevated in MetS + RAS. Renal oxidative stress and TNF-α expression increased in ARAS and further in MetS + RAS, which also upregulated expression of anti-angiogenic angiostatin, and magnified apoptosis, tubular injury, and fibrosis.

Conclusion: Beyond dyslipidemia, obesity and insulin-resistance aggravate damage in the post-stenotic kidney in MetS, despite relative hyperfiltration-related preservation of renal function. These observations underscore the need to control systemic metabolic disturbances in order to curb renal damage in subjects with ischemic kidney disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430139PMC
August 2021

Sex differences in cognitive function of first-diagnosed and drug-naïve patients with bipolar disorder.

J Affect Disord 2021 Sep 3;295:431-437. Epub 2021 Sep 3.

Department of Psychiatry, National Clinical Research Center for Mental Disorders, China National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China. Electronic address:

Background: Bipolar disorder (BD) is a severe mental illness that affects more than 1% the world's population with high recurrence rates and a series of comorbidities. Cognitive dysfunction is an endophenotype of BD, but sex influences in cognitive impairment remains unclear.

Method: We evaluated the performance of 139 patients with first-diagnosed, drug-naïve BD (44 males and 95 females) and 92 healthy controls (24 males and 68 females) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale and the Stroop color-word test.

Result: Immediate memory, visuospatial/constructional ability, language, attention, delayed memory, total RBANS score, and Stroop color-word scores were significantly lower in patients with first-diagnosed, drug-naïve BD than healthy participants. Thus, male patients had worse attention and delayed memory scores compared with female patients with BD. Importantly, a worse performance in visuospatial/constructional ability was negatively associated with the Young Mania Rating Scale score in male patients only.

Conclusion: Male patients with first-diagnosed, drug-naïve bipolar disorder had worse cognitive dysfunction than female patients in attention and delayed memory. Cognitive deficits were correlated with mania severity only in male patients. These findings reveal the sexual dimorphism in the cognitive deficits of early BD patients with mild and moderated symptoms for further pathophysiological exploration.
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http://dx.doi.org/10.1016/j.jad.2021.08.125DOI Listing
September 2021

Two Novel Pathogenic Variants of Gene and the Underlying Molecular Mechanisms in Progressive Familial Intrahepatic Cholestasis Type 4 Patients.

Front Cell Dev Biol 2021 24;9:661599. Epub 2021 Aug 24.

Department of Medical Imaging Center, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.

Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease that accounts for 10%-15% childhood cholestasis and could lead to infant disability or death. There are three well-established types of PFIC (1-3), caused by mutations in the , , and genes. Biallelic pathogenic variants in the tight junction protein 2 gene () were newly reported as a cause for PFIC type 4; however, only a limited number of patients and undisputable variants have been reported for , and the underlying mechanism for PFIC 4 remains poorly understood. To explore the diagnostic yield of analysis in suspected PFIC patients negative for the PFIC1-3 mutation, we designed a multiplex polymerase chain reaction-based next-generation sequencing method to analyze gene variants in 267 PFIC patients and identified biallelic rare variants in three patients, including three known pathogenic variants and two novel variants in three patients. By using CRISPR-cas9 technology, we demonstrated that c.1202A > G was pathogenic at least partially by increasing the expression and nuclear localization of TJP2 protein. With the minigene assay, we showed that c.2668-11A > G was a new pathogenic variant by inducing abnormal splicing of gene and translation of prematurely truncated TJP2 protein. Furthermore, knockdown of TJP2 protein by siRNA technology led to inhibition of cell proliferation, induction of apoptosis, dispersed F-actin, and disordered microfilaments in LO2 and HepG2celles. Global gene expression profiling of TJP2 knockdown LO2 cells and HepG2 cells identified the dysregulated genes involved in the regulation of actin cytoskeleton. Microtubule cytoskeleton genes were significantly downregulated in TJP2 knockdown cells. The results of this study demonstrate that TJP2 c.1202A > G and TJP2 c.2668-11A > G are two novel pathogenic variants and the cytoskeleton-related functions and pathways might be potential molecular pathogenesis for PFIC.
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http://dx.doi.org/10.3389/fcell.2021.661599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421653PMC
August 2021

Fetoscopy-guided bipolar cord coagulation in selective fetal reduction with complicated monochorionic diamniotic twins: a prospective cohort study.

J Matern Fetal Neonatal Med 2021 Sep 1:1-4. Epub 2021 Sep 1.

Department of Obstetrics and Gynecology, the Affiliated Drum and Tower Hospital of Medical School of Nanjing University, Nanjing, China.

Objective: To assess the feasibility of fetoscopy-guided bipolar umbilical cord coagulation for selective fetal reduction in complicated monochorionic diamniotic (MCDA) twin pregnancies.

Methods: MCDA twins undergoing fetoscopy-guided bipolar cord coagulation (BCC) were enrolled prospectively between December 2015 to March 2020 in a fetal medicine center.

Results: Twenty-three cases undergoing fetoscopy-guided BCC were finally analyzed, including 11 cases for type 2 selective intrauterine growth restriction, 4 cases for twin-twin transfusion syndrome, and 8 cases for a severe discordant anomaly. The overall survival rate was 78.3% (18/23).

Conclusions: Fetoscopy-guided BCC is effective for selective fetal reduction in complicated monochorionic twin pregnancies.
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http://dx.doi.org/10.1080/14767058.2021.1961725DOI Listing
September 2021

The different correlations between obesity and osteoporosis after adjustment of static mechanical loading from weight and fat free mass.

J Musculoskelet Neuronal Interact 2021 09;21(3):351-357

Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, P. R. China.

Objectives: To explore complex correlations between obesity (OB) and osteoporosis (OP) after adjustment of static mechanical loading from weight and fat free mass (FFM).

Methods: A total of 3749 Chinese aged ≥65 years were selected from our ongoing cohort study. OB indices and bone mineral density (BMD) were measured for each subject. Linear regression analyses were performed to explore the correlations between OB indices and OP under three adjustment models (unadjusted, adjusted with weight and adjusted with FFM).

Results: Under no adjustment, three general obesity indices (body mass index: BMI, fat mass: FM, and percentage FM: PFM) were positively associated with BMD at three skeletal sites (P<0.001) in the regression analyses. However, after the adjustment with weight, these associations were mostly significant but reverse i.e., negatively in direction. After adjustment with FFM, the three indices were still positively and significantly (P<0.001) associated with BMD but regression coefficients were smaller compared to the unadjusted associations. Similar associations were observed for central adiposity and lower limb adiposity indices.

Conclusions: The combined relation of OB to OP due to the physiological factors secreted from adipose tissues and the static mechanical loading from FM is positive in direction.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426647PMC
September 2021

Multiplex immunohistochemistry indicates biomarkers in colorectal cancer.

Neoplasma 2021 Aug 31. Epub 2021 Aug 31.

Yunnan Digestive Endoscopy Clinical Medical Center, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, whose survival ratio and indicating biomarkers are limited. The rapid development of multiple immunofluorescences gives rise to widespread applications of this new advanced technology called multiplex immunohistochemistry (mIHC), which makes it possible to detect several fluorescent proteins on the same tumor tissue microarray (TMA) within the same time and spatial organization. By taking advantage of this mIHC technology, we detected three tumor-associated antigens (TAA) including the human epidermal growth factor receptor 2 (HER2), the cluster of differentiation 133 (CD133), the programmed death ligand-1 (PD-L1), and one immune-associated macrophage marker, the cluster of differentiation 68 (CD68) in cancer tissues versus para-carcinomatous normal tissues derived from a cohort of 84 CRC patients. All four markers were upregulated in cancer tissue compared with normal tissues. And the expressions of CD133, HER2, PD-L1, and CD68 were correlated with pathological grade, T stage, tumor size, metastasis, respectively. Accordingly, CD133 and PD-L1 could be applied as potential diagnostic biomarkers for CRC at an early stage, while the enrichment of HER2 might act as an advanced indicator in aggressive cancer status of CRC; whereas, CD68 could be potentially considered as an advanced diagnostic indicator in CRC patients, as well as a metastatic promoter in CRC-related TME. The differential expression of these four proteins, as well as their clinicopathological correlation, indicates that these four proteins could be utilized as specific diagnostic and prognostic biomarkers in CRC patients.
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http://dx.doi.org/10.4149/neo_2021_210312N324DOI Listing
August 2021

Rictor is involved in deletion-induced impairment of spatial learning and memory but not autism-like behaviors.

Front Biosci (Landmark Ed) 2021 Aug;26(8):335-346

Cerebrovascular Disease Laboratory, Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China.

: The gene which encodes a δ-catenin protein (CTNND2) is associated with multiple severe neurological disorders. However, the specific role of in spatial cognition and related mechanisms remains obscure. : In this study, we generated a new line of -Knock out (KO) mice with its exon2 deleted, and then characterized their behavioral phenotypes and explore the Biological mechanism. : -KO mice were with typical autism-like behaviors as evidenced by reduced social interaction in three-chamber sociability test, more frequent stereotypic behaviors (self-grooming), and deficits in spatial learning and memory tested by the Morris water maze. Furthermore, the expression of Rictor protein, a core component of the mTORC2 complex, was significantly decreased in the hippocampus of mutant mice. ShRNA-induced knockdown of Rictor protein in the hippocampus of both -KO mice and wild-type mice exacerbated spatial learning and memory deficits but did not affect their autism-like behaviors. Mechanistically, the hippocampal CA1 neurons of -KO mice showed decreased actin polymerization, postsynaptic spine density. Down-regulation of Rictor resulted in altered expression of post-synaptic proteins such as GluR1 and ELKS, but not presynaptic protein Synapsin1, implying abnormal synaptic changes in KO mice. : The gene is involved in spatial learning and memory via Rictor-mediated actin polymerization and synaptic plasticity. Our study provides a novel insight into the role and mechanisms of the gene in cognition at the molecular and synaptic levels.
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http://dx.doi.org/10.52586/4947DOI Listing
August 2021

Dissociation Pattern in Default-Mode Network Homogeneity in Drug-Naive Bipolar Disorder.

Front Psychiatry 2021 9;12:699292. Epub 2021 Aug 9.

National Clinical Research Center for Mental Disorders, Department of Psychiatry, China National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.

Default mode network (DMN) plays a key role in the pathophysiology of in bipolar disorder (BD). However, the homogeneity of this network in BD is still poorly understood. This study aimed to investigate abnormalities in the NH of the DMN at rest and the correlation between the NH of DMN and clinical variables in patients with BD. Forty drug-naive patients with BD and thirty-seven healthy control subjects participated in the study. Network homogeneity (NH) and independent component analysis (ICA) methods were used for data analysis. Support vector machines (SVM) method was used to analyze NH in different brain regions. Compared with healthy controls, significantly increased NH in the left superior medial prefrontal cortex (MPFC) and decreased NH in the right posterior cingulate cortex (PCC) and bilateral precuneus were found in patients with BD. NH in the right PCC was positively correlated with the verbal fluency test and verbal function total scores. NH in the left superior MPFC was negatively correlated with triglyceride (TG). NH in the right PCC was positively correlated with TG but negatively correlated with high-density lipoprotein cholesterol (HDL-C). NH in the bilateral precuneus was positively correlated with cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, NH in the left superior MPFC showed high sensitivity (80.00%), specificity (71.43%), and accuracy (75.61%) in the SVM results. These findings contribute new evidence of the participation of the altered NH of the DMN in the pathophysiology of BD.
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http://dx.doi.org/10.3389/fpsyt.2021.699292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380964PMC
August 2021

Association of phenotypic transformation of circulating tumor cells and early recurrence in patients with hepatocellular carcinoma following liver transplantation.

Asian J Surg 2021 Aug 20. Epub 2021 Aug 20.

Department of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, Organ Transplantation Research Center of Guangdong Province. Guangzhou, Guangdong, China; Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Background: CTCs play a critical role in the diagnosis and prognosis of liver cancer. However, there are few studies on whether different types of CTCs can predict the prognosis in patients with HCC following LT.

Methods: Retrospective data including CTCs detected by the CanPatrolTM platform combined with RNA-ISH were collected and analyzed on 56 patients from December 2016 to December 2019 at the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.

Results: During the study period, fifty-six patients (51 males, 5 females) were included with an mean age of 52 ± 9 years. The 1-, 2- and 3-year recurrence rates of postoperative interstitial CTC-positive and CTC-negative groups were 21.7% vs 10.8%, 37.5% vs 10.8% and 55.5% vs 10.8%, confirming a statistically significant difference between the 2 groups (p = 0.044). The 1-, 2- and 3-year recurrence rates of the increasing interstitial CTCs group were 25.2%, 36.9% and 66.9%, while 12.6%, 24.4% and 24.4% in the decreasing and unchanged group, indicating a significant difference (p = 0.038).

Conclusion: CanPatrolTM platform presents a superior analytical sensitivity, and may be used as a dynamic monitoring tool for CTCs. And interstitial CTCs which are more aggressive and metastatic caused by EMT can be regarded as a predictor of post-transplant tumor recurrence after LT for HCC.
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http://dx.doi.org/10.1016/j.asjsur.2021.07.058DOI Listing
August 2021

HS-GC-IMS detection of volatile organic compounds in Acacia honey powders under vacuum belt drying at different temperatures.

Food Sci Nutr 2021 Aug 24;9(8):4085-4093. Epub 2021 Jun 24.

College of Biochemical Engineering Beijing Union University Beijing China.

Honey is a commodity of great nutritional value, but deep-processed honey products are uncommon. Herein, we used vacuum belt dryer to dry Acacia honey at 60°C, 70°C, and 80°C, prepared it into powder, and analyzed its volatile compound differences. We established HS-GC-IMS method to detect the volatile organic compounds (VOCs) of these three Acacia honey powders (AHPs). In total, 77 peaks were detected, and 23 volatile compounds were identified, including eight aldehydes, six ketones, three furans, one alcohol, one phenol, one lactone, one ester, one acid, and one nitrile. Moreover, principal component analysis (PCA) and fingerprint similarity analysis based on the Euclidean distance distinguished the three heating temperature treatments. Clearly, it was concluded that there are significant differences in volatile substances at different tested temperatures, and when the AHP was incubated at 80°C, more volatile compounds were detected.
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http://dx.doi.org/10.1002/fsn3.2364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358364PMC
August 2021

2D Silicate Materials for Composite Polymer Electrolytes.

Chem Asian J 2021 Aug 11. Epub 2021 Aug 11.

School of Optical and Electronic Information, Wuhan National Laboratory for Optoelectronics (WNLO), Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.

Two-dimensional (2D) silicate materials have become one of the promising candidates for constructing composite polymer electrolytes due to their advantages of low cost, high stability, good mechanical property, high ionic conductivity and potential to inhibit the growth of lithium dendrites. However, the application of 2D silicate materials in composite polymer electrolytes (CPEs) is still at the infancy stage and facing a lot of challenges. In this minireview, we summarize the structures and properties of 2D silicate materials that have been applied in CPEs, the processing methods of composite electrolytes based on 2D silicates, and the recent process of 2D silicate materials in CPEs. We hope this review could present a general overview of the 2D silicates for CPEs and promote the further study for potential applications.
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http://dx.doi.org/10.1002/asia.202100838DOI Listing
August 2021

The complete chloroplast genome of ornamental plant C.Wright (Acanthaceae).

Mitochondrial DNA B Resour 2021 17;6(7):2017-2018. Epub 2021 Jun 17.

College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou City, P.R. China.

C.Wright is a perennial plant of the Acanthaceae, which has significant ornamental value. Because of its strong adaptability, it is widely planted in Chinese rural areas. Based on sequencing data from Illumina, the first complete chloroplast (cp) genome of C.Wright is reported in this paper. This cp genome was 143,016bp in length, including a large single-copy region (LSC) of 91,857bp, a small single-copy (SSC) of 17,591bp and two inverted repeat regions (IRs) of 16,784bp. It contained 128 genes, 35 transfer RNA genes, 8 ribosomal RNA genes, with an overall GC content of 38.41%. Additionally, the phylogenetic analysis showed that is closely related to (NC_037485) (MT576695) and (NC_039762). The results of this study provide valuable information for the continued study of its species evolution, genetic engineering and germplasm resource utilization.
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http://dx.doi.org/10.1080/23802359.2021.1935347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344733PMC
June 2021

Prenatal genetic diagnosis of omphalocele by karyotyping, chromosomal microarray analysis and exome sequencing.

Ann Med 2021 12;53(1):1285-1291

Gentic Medical Center, Guangdong Women and Children Hospital, Guangzhou, PR China.

Objectives: The aim of this study is to share our experience in the prenatal diagnosis of omphalocele by karyotyping, chromosomal microarray analysis (CMA) and whole exome sequencing (WES).

Methods: In this retrospective study, 81 cases of omphalocele were identified from 2015 to 2020. Associated anomalies and prenatal diagnosis based on karyotyping, CMA and WES were analysed.

Results: Fifty-eight (71.6%) of the 81 foetuses had other ultrasound anomalies. Giant omphalocele was present in 11 cases (13.6%) and small omphalocele was present in 70 cases (86.4%). Chromosomal abnormalities were found in 24 foetuses (29.6%, 24/81), the most common of which were trisomy 18 (58.8%, 11/24) and trisomy 13 (29.2%, 7/24). Compared to isolated omphalocele, non-isolated omphalocele was accompanied by an increased prevalence of chromosomal abnormalities (4.3% (1/23) 39.7% (23/58),  = 8.226,  = .004). All chromosomal abnormalities were found in small omphalocele. Aside from aneuploidy, CMA showed one pathogenic copy number variants (CNVs) for a detection rate of 1.2%, one variants of unknown significance (VOUS) and one instance of loss of heterozygosity (LOH). WES was performed on 3 non-isolated cases, and one was found to have pathogenic variants.

Conclusions: The most common genetic cause of omphalocele is aneuploidy and the prevalence of chromosomal abnormalities is increased with non-isolated and small omphalocele. CMA and WES can be useful for providing further genetic information to assist in prenatal counselling and pregnancy management.
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http://dx.doi.org/10.1080/07853890.2021.1962966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366676PMC
December 2021

Selective detection of glutathione by flower-like NiVO with only peroxidase-like activity at neutral pH.

Talanta 2021 Nov 25;234:122645. Epub 2021 Jun 25.

College of Science, Harbin Institute of Technology, Shenzhen, 518055, China; College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China. Electronic address:

In view of the broad application prospect of peroxidase-like nanozymes in biomedical analysis, it is of great significance to eliminate the interference of their oxidase-like activity and enable them to work under neutral conditions. Herein, flower-like NiVO was synthesized and their enzyme-mimicking activity was investigated. Through the regulation of pH, NiVO nanozyme showed only peroxidase-like activity but not oxidase-like activity under neutral conditions, which could catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine into its blue product in the presence of HO. Furthermore, based on the competitive effect of glutathione (GSH) on the catalytic activity of nanozymes, a semi-quantitative/quantitative colorimetric assay was established for GSH detection by using peroxidase-like NiVO. The assay exhibited a good linear relationship in GSH concentration ranging from 3-100 μmol L, with a detection limit of 0.89 μmol L. Moreover, in the presence of formaldehyde as masking agent, this method showed satisfactory specificity for GSH under the interference of a variety of interfering substances and even biothiols. Concerning the practical application, the system was applied to monitor GSH level in fetal bovine serum, human serum and SiHa cells. Satisfyingly, the obtained results were consistent well with those of Ultra performance liquid chromatography (UPLC) and assay kit, indicating the constructed assay has great potential in clinical application.
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http://dx.doi.org/10.1016/j.talanta.2021.122645DOI Listing
November 2021

Flavonoids in Ampelopsis grossedentata as covalent inhibitors of SARS-CoV-2 3CL: Inhibition potentials, covalent binding sites and inhibitory mechanisms.

Int J Biol Macromol 2021 Sep 30;187:976-987. Epub 2021 Jul 30.

Shanghai Frontiers Science Center for Chinese Medicine Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:

Coronavirus 3C-like protease (3CL) is a crucial target for treating coronavirus diseases including COVID-19. Our preliminary screening showed that Ampelopsis grossedentata extract (AGE) displayed potent SARS-CoV-2-3CL inhibitory activity, but the key constituents with SARS-CoV-2-3CL inhibitory effect and their mechanisms were unrevealed. Herein, a practical strategy via integrating bioactivity-guided fractionation and purification, mass spectrometry-based peptide profiling and time-dependent biochemical assay, was applied to identify the crucial constituents in AGE and to uncover their inhibitory mechanisms. The results demonstrated that the flavonoid-rich fractions (10-17.5 min) displayed strong SARS-CoV-2-3CL inhibitory activities, while the constituents in these fractions were isolated and their SARS-CoV-2-3CL inhibitory activities were investigated. Among all isolated flavonoids, dihydromyricetin, isodihydromyricetin and myricetin strongly inhibited SARS-CoV-2 3CL in a time-dependent manner. Further investigations demonstrated that myricetin could covalently bind on SARS-CoV-2 3CL at Cys300 and Cys44, while dihydromyricetin and isodihydromyricetin covalently bound at Cys300. Covalent docking coupling with molecular dynamics simulations showed the detailed interactions between the orthoquinone form of myricetin and two covalent binding sites (surrounding Cys300 and Cys44) of SARS-CoV-2 3CL. Collectively, the flavonoids in AGE strongly and time-dependently inhibit SARS-CoV-2 3CL, while the newly identified SARS-CoV-2 3CL inhibitors in AGE offer promising lead compounds for developing novel antiviral agents.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322037PMC
September 2021

TSC1/2 mutations-a unique type of mutation suitable for liver transplantation of Hepatocellular carcinoma.

J Gastrointest Oncol 2021 Jun;12(3):1074-1085

Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: This study aimed to investigate the relationship between the prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation and mammalian target of rapamycin (mTOR) pathway-related genes-.

Methods: We retrospectively analyzed the clinical data of 46 patients who underwent liver transplantation for HCC and performed next generation sequencing to analyze the relationship between the efficacy of sirolimus after liver transplantation for HCC and mutations in mTOR pathway-related genes, especially tuberous sclerosis complex (TSC) mutations.

Results: The average age of 46 patients with liver transplantation for HCC was 51±21 years. After surgery, 35 patients received an anti-rejection/anti-tumor regimen that included sirolimus, and 11 patients did not receive sirolimus. There was no significant difference in survival rate between the two groups (P=0.761). The gene sequencing results showed mTOR-related pathway mutations in 10 patients, of whom five (10.9%) had TSC1/2 mutations. Of the 35 patients using sirolimus, those with mTOR-related mutations had significantly better survival rates than patients without mTOR-related mutations (P=0.016).

Conclusions: According to genetic sequencing results, a personalized treatment plan for specific genetic mutations should be selected in patients undergoing liver transplantation for HCC. Patients with mTOR-related gene mutations, especially TSC mutations, can gain significant benefits from the use of mTOR inhibitors such as sirolimus.
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http://dx.doi.org/10.21037/jgo-20-378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261316PMC
June 2021

Whole-exome sequencing identified a novel mutation in of a Chinese family.

J Genet 2021 ;100

Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People's Republic of China.

Choroideraemia (CHM) is a rare X-linked progressive-inherited retinal disease. In this study, we diagnosed and explored the genetic cause in a Chinese pedigree exhibiting nyctalopia and decreased visual acuity in early life. Clinical data and peripheral blood samples were collected from available family members. Sanger sequencing of and genes, and subsequently whole-exome sequencing was carried out to investigate the molecular cause. The proband was initially diagnosed as retinitis pigmentosa and experienced night blindness at an early age and decreased visual acuity in teens. The other affected males in this family suffered from the same problem. Direct sequencing failed to reveal the genetic cause and hence a novel hemizygous mutation c.861_862insGCTT was detected by WES in gene resulting in a premature stop codon and a truncated protein. Subsequently, it was confirmed by Sanger sequencing and cosegregation analysis. We describe a novel mutation c.861_862insGCTT in gene in a Chinese pedigree with choroideraemia. Our study emphasizes the utilization of next-generation sequencing in the diagnosis and genetic analysis of retinal diseases.
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September 2021

Renal Revascularization Attenuates Myocardial Mitochondrial Damage and Improves Diastolic Function in Pigs with Metabolic Syndrome and Renovascular Hypertension.

J Cardiovasc Transl Res 2021 Jul 16. Epub 2021 Jul 16.

Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Percutaneous transluminal renal angioplasty (PTRA) may improve cardiac function in renovascular hypertension (RVH), but its effect on the biological mechanisms implicated in cardiac damage remains unknown. We hypothesized that restoration of kidney function by PTRA ameliorates myocardial mitochondrial damage and preserves cardiac function in pigs with metabolic syndrome (MetS) and RVH. Pigs were studied after 16 weeks of MetS+RVH, MetS+RVH treated 4 weeks earlier with PTRA, and Lean and MetS Sham controls (n=6 each). Cardiac function was assessed by multi-detector CT, whereas cardiac mitochondrial morphology and function, microvascular remodeling, and injury pathways were assessed ex vivo. PTRA attenuated myocardial mitochondrial damage, improved capillary and microvascular maturity, and ameliorated oxidative stress and fibrosis, in association with attenuation of left ventricular remodeling and diastolic dysfunction. Myocardial mitochondrial damage correlated with myocardial injury and renal dysfunction. Preservation of myocardial mitochondria with PTRA can enhance cardiac recovery, underscoring its therapeutic potential in experimental MetS+RVH.
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http://dx.doi.org/10.1007/s12265-021-10155-3DOI Listing
July 2021

Unidirectional large-scale waveguide grating with uniform radiation for optical phased array.

Opt Express 2021 Jun;29(13):20995-21010

Two novel waveguide gratings for optical phased array transmitters are investigated. By offsetting the grating structures along the waveguide on the upper and lower surfaces of the silicon nitride (SiN) waveguide, the dual-level chain and dual-level fishbone structures can achieve 95% of unidirectional radiation with a single SiN layer by design. With apodized perturbation along the gratings, both structures can achieve uniform radiation without compromising the unidirectional radiation performance. In experiment, both demonstrate ∼ 80-90% unidirectionality. With further analysis, it is found that the dual-level fishbone structure is more feasible and robust to process variations in uniform radiation.
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http://dx.doi.org/10.1364/OE.427999DOI Listing
June 2021

YAP-Dependent Induction of CD47-Enriched Extracellular Vesicles Inhibits Dendritic Cell Activation and Ameliorates Hepatic Ischemia-Reperfusion Injury.

Oxid Med Cell Longev 2021 22;2021:6617345. Epub 2021 Jun 22.

Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Hepatic ischemia-reperfusion injury (IRI) is the most common cause of liver damage leading to surgical failures in hepatectomy and liver transplantation. Extensive inflammatory reactions and oxidative responses are reported to be the major processes exacerbating IRI. The involvement of Yes-associated protein (YAP) in either process has been suggested, but the role and mechanism of YAP in IRI remain unclear. In this study, we constructed hepatocyte-specific YAP knockout (YAP-HKO) mice and induced a hepatic IRI model. Surprisingly, the amount of serum EVs decreased in YAP-HKO compared to WT mice during hepatic IRI. Then, we found that the activation of YAP increased EV secretion through F-actin by increasing membrane formation, while inhibiting the fusion of multivesicular body (MVB) and lysosomes in hepatocytes. Further, to explore the essential elements of YAP-induced EVs, we applied mass spectrometry and noticed CD47 was among the top targets highly expressed on hepatocyte-derived EVs. Thus, we enriched CD47 EVs by microbeads and applied the isolated CD47 EVs on IRI mice. We found ameliorated IRI symptoms after CD47 EV treatment in these mice, and CD47 EVs bound to CD172 on the surface of dendritic cells (DCs), which inhibited DC activation and the cascade of inflammatory responses. Our data showed that CD47-enriched EVs were released in a YAP-dependent manner by hepatocytes, which could inhibit DC activation and contribute to the amelioration of hepatic IRI. CD47 EVs could be a potential strategy for treating hepatic IRI.
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http://dx.doi.org/10.1155/2021/6617345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241504PMC
June 2021

[Simultaneous determination of three quaternary ammonium muscle relaxants in blood by high performance liquid chromatography-tandem mass spectrometry].

Se Pu 2021 Jul;39(7):695-701

State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China.

Vecuronium, rocuronium, and pancuronium are widely used as non-depolarizing muscle relaxants. There have been occasional cases of allergic reactions and even death when using such muscle relaxants. Rapid determination of the concentration of these muscle relaxants in blood can provide valuable information for early clinical diagnosis. As quaternary ammonium compounds, these muscle relaxants are highly polar. Hence, they cannot be retained effectively on reversed-phase chromatographic columns with conventional mobile phases. These quaternary ammonium muscle relaxants are mainly separated by ion-pair chromatography. Using an ion-pairing reagent can help improve the retention capabilities of quaternary ammonium muscle relaxants. Nevertheless, the sensitivity of MS detection is significantly decreased because of ionic inhibition caused by the ion-pairing reagent in the mobile phase. Furthermore, ion-pairing reagents can pollute the MS system. A method based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the simultaneous determination of the three quaternary ammonium muscle relaxants in blood. The blood samples were diluted and subjected to high-speed centrifugation. The supernatant was purified on a Bond Elut AL-N solid phase extraction column and then filtered through a 0.45 μm microporous membrane. The quaternary ammonium muscle relaxants were separated on a ZIC-cHILIC analytical column (50 mm×2.1 mm, 3.0 μm) with gradient elution. Acetonitrile and 0.1% formic acid aqueous solution were used as mobile phases. The separated compounds were analyzed by tandem MS with an electrospray ionization (ESI) source in positive and multiple reaction monitoring (MRM) modes. The matrix effects of vecuronium, rocuronium, and pancuronium in blood were 88.1% to 95.4%. The calibration curves for vecuronium, rocuronium, and pancuronium showed good linear relationships in each range, and all correlation coefficients () were > 0.996. The limits of detection of vecuronium, rocuronium, and pancuronium were 0.2-0.8 ng/mL, with the corresponding limits of quantification being 0.5-2.0 ng/mL. The recoveries of vecuronium, rocuronium, and pancuronium were 92.8% to 110.6%, with relative standard deviations (RSDs) of 3.2%-9.4%. This method is sensitive, accurate, and easy to operate, and it can be used to rapidly determine vecuronium, rocuronium, and pancuronium in blood.
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http://dx.doi.org/10.3724/SP.J.1123.2020.09020DOI Listing
July 2021

Increased Global-Brain Functional Connectivity Is Associated with Dyslipidemia and Cognitive Impairment in First-Episode, Drug-Naive Patients with Bipolar Disorder.

Neural Plast 2021 5;2021:5560453. Epub 2021 Jun 5.

National Clinical Research Center on Mental Disorders and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.

Objectives: Previous researches have demonstrated that abnormal functional connectivity (FC) is associated with the pathophysiology of bipolar disorder (BD). However, inconsistent results were obtained due to different selections of regions of interest in previous researches. This study is aimed at examining voxel-wise brain-wide functional connectivity (FC) alterations in the first-episode, drug-naive patient with BD in an unbiased way.

Methods: A total of 35 patients with BD and 37 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Global-brain FC (GFC) was applied to analyze the image data. Support vector machine (SVM) was adopted to probe whether GFC abnormalities could be used to identify the patients from the controls.

Results: Patients with BD exhibited increased GFC in the left inferior frontal gyrus (LIFG), pars triangularis and left precuneus (PCu)/superior occipital gyrus (SOG). The left PCu belongs to the default mode network (DMN). Furthermore, increased GFC in the LIFG, pars triangularis was positively correlated with the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with the scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) coding test and Stroop color. Increased GFC values in the left PCu/SOG can be applied to discriminate patients from controls with preferable sensitivity (80.00%), specificity (75.68%), and accuracy (77.78%).

Conclusions: This study found increased GFC in the brain regions of DMN; LIFG, pars triangularis; and LSOG, which was associated with dyslipidemia and cognitive impairment in patients with BD. Moreover, increased GFC values in the left PCu/SOG may be utilized as a potential biomarker to differentiate patients with BD from controls.
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http://dx.doi.org/10.1155/2021/5560453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203345PMC
June 2021

Low BDNF levels in serum are associated with cognitive impairments in medication-naïve patients with current depressive episode in BD II and MDD.

J Affect Disord 2021 10 18;293:90-96. Epub 2021 Jun 18.

National Clinical Research Center for Mental Disorders, Department of Psychiatry, China National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China. Electronic address:

Objective: This study aimed to investigate the role of Brain-derived neurotrophic factor (BDNF) in clinical and cognitive outcomes in medication-naïve patients with Bipolar type II disorder (BD II) and Major depressive disorder (MDD).

Methods: 45 outpatients with BD II, 40 outpatients with MDD and 40 healthy controls (HCs) were recruited, and sociodemographic and clinical data were collected. Their BDNF serum levels were measured and analyzed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Results: BDNF levels were significantly lower in BD II patients than in MDD patients and HCs (p = 0.001). BD II and MDD patients had similar cognitive performance deficits shown on Attention (p = 0.001), Delayed memory (p = 0.001), and RBANS total score (p = 0.001). BDNF levels were positively associated with Visuospatial / constructional and Stroop color-word in BD II group, and with language in MDD group. The area under the curve (AUC) of the ROC analysis in BD II vs. MDD was 0.664, therefore, BDNF levels could not distinguish BD II from MDD.

Conclusion: Our study showed the decreased serum BDNF in MDD and BD II patients, suggesting BDNF may be involved in the pathophysiology of MDD and BD II. BDNF and cognitive deficits are both of low efficiency in distinguishing BD II from MDD. Decrease of BDNF may potentially indicate cognitive dysfunction in BD II and MDD patients with a current depressive episode.
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http://dx.doi.org/10.1016/j.jad.2021.06.018DOI Listing
October 2021

[Application advances in the computational fluid dynamics in tissue engineering].

Authors:
Hui Tang Jinjin Wu

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jun;35(6):776-780

Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, 400042, P.R.China.

Objective: To review the advances in the computational fluid dynamics (CFD) in tissue engineering.

Methods: The latest research of CFD applied to tissue engineering were extensively retrieved and analyzed, the optimization of bioreactor design and the simulation of fluid dynamics and cell growth kinetics during tissue regeneration were mainly reviewed.

Results: The simulation and predictive capabilities of CFD can provide important guidance for the optimization of bioreactor design, and the cultivation of engineering tissue. The accuracy of model prediction results can be further improved by combining with experimental research.

Conclusion: As a new and effective research tool, CFD has its unique advantages in the application of tissue engineering. However, a more comprehensive and accurate simulation of the whole process of tissue regeneration still needs further studies.
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http://dx.doi.org/10.7507/1002-1892.202012098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218176PMC
June 2021

Risk factors for the mortality of hemodialysis patients with COVID-19: A multicenter study from the overall hemodialysis population in Wuhan.

Semin Dial 2021 Jun 16. Epub 2021 Jun 16.

Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Introduction: Maintenance hemodialysis (MHD) patients are highly threatened in the novel coronavirus disease 2019 (COVID-19) pandemic, but evidence of risk factors for mortality in this population is still lacking.

Methods: We followed outcomes of the overall MHD population of Wuhan, including 7154 MHD patients from 65 hemodialysis centers, from January 1 to May 4, 2020. Among them, 130 were diagnosed with COVID-19. The demographic and clinical data of them were collected and compared between survivors and nonsurvivors.

Results: Compared to the corresponding period of last year, the all-cause mortality rate of the Wuhan MHD population significantly rose in February, and dropped down in March 2020. Of the 130 COVID-19 cases, 51 (39.2%) were deceased. Advanced age, decreased oxygen saturation, low diastolic blood pressure (DBP) on admission, and complications including acute cardiac injury (HR 5.03 [95% CI 2.21-11.14], p < 0.001), cerebrovascular event (HR 2.80 [95% CI 1.14-6.86], p = 0.025) and acute respiratory distress syndrome (HR 3.50 [95% CI 1.63-7.51], p = 0.001) were identified as independent risk factors for the death of COVID-19. The median virus shedding period of survivors was 25 days, longer than the general population.

Conclusions: Maintenance hemodialysis patients are a highly vulnerable population at increased risk of mortality and prolonged virus shedding period in the ongoing COVID-19 pandemic. Advanced age, decreased oxygen saturation, low DBP on admission, and complications like acute cardiac injury are parameters independently associated with poor prognosis.
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http://dx.doi.org/10.1111/sdi.12995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447194PMC
June 2021

Plasma DNA Integrity as a Prognostic Biomarker for Colorectal Cancer Chemotherapy.

J Oncol 2021 26;2021:5569783. Epub 2021 May 26.

Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Objectives: To verify whether the concentrations and integrity index of circulating cell-free DNA (cfDNA) in serum may be clinically useful for the progression monitoring of colorectal cancer (CRC) patients.

Methods: Serum samples were collected from 76 primary CRC patients who underwent surgery, including 60 with chemotherapy and 43 with follow-up. Long (247 bp) and short (115 bp) DNA fragments in serum were detected by real-time quantitative PCR by amplifying the ALU repeats. Ten serum traditional biomarkers levels were detected by chemiluminescence immunoassay assay.

Results: The median DNA integrity index (ALU247/ALU115) of serum DNA in the preoperative group was significantly higher than those in the postchemotherapy and the follow-up groups, while cfDNA concentration (ALU115) was significantly lower in the preoperative group compared with the postchemotherapy and the follow-up groups. CEA and CA242 were significantly lower in the postoperative group than in the preoperative group.

Conclusions: Serum DNA integrity index (ALU247/115) may prove to be a promising candidate biomarker for prognostic prediction of CRC who underwent chemotherapy and during short-term follow-up.
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http://dx.doi.org/10.1155/2021/5569783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175143PMC
May 2021

Association of T2285C polymorphism in PARP1 gene coding region with its expression, activity and NSCLC risk along with prognosis.

Mutagenesis 2021 Aug;36(4):281-293

Emergency Center, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.

Poly (ADP-ribose) polymerase-1 (PARP1), a DNA repair gene, is the crucial player in the maintenance of genome integrity. T2285C polymorphism in coding region of PARP1 has been reported to be associated with susceptibility to tumours. We explored the relationship and mechanism of T2285C polymorphism of PARP1 to its expression and activity along with risk and prognosis in non-small cell lung cancer (NSCLC). mRNA expression was measured using quantitative RT-PCR assay or collected from TCGA dataset. Protein expression was examined with immunoblotting assay. Genotypes were determined by PCR-RFLP and sequencing approaches. PARP1 activity was determined with enzyme activity assay. Regulation of SIRT7 to PARP1 was determined by overexpression and small interference experiment. Association of PARP1 T2285C polymorphism with NSCLC risk was evaluated via multiple logistic regression analysis. Comparison of treatment response and progression-free survival (PFS) of NSCLC patients among different genotypes or regimens was made by chi-square test. Results indicated that mRNA and protein expression of PARP1 dramatically increased in NSCLC tissues in comparison with paired para-carcinoma tissues (P < 0.05). TC/CC mutant genotypes were associated with markedly enhanced PARP1 mRNA level compared with TT genotype (P = 0.011). No significant difference was discovered in PARP1 protein expression among TT, TC or CC genotypes (P > 0.05). Subjects with variant allele C had higher risk of NSCLC in comparison with allele T carriers [odds ratio = 1.560; P = 0.000]. NSCLC patients carrying mutational TC or CC genotypes were correlated with unfavourable response to platinum-based chemotherapy (TT vs. TC vs. CC, P = 0.010), and shorter PFS compared with TT genotype (TT vs. TC vs. CC, P = 0.009). T2285C mutation of PARP1 resulted in the enhancement of its mRNA, but the decrease of enzyme activity in tumour cell. Overexpression of SIRT7 attenuated PARP1 expression and activity. These findings suggest the variant allele C of T2285C polymorphism of PARP1 linked to an increase of NSCLC risk, and unfavourable efficacy and prognosis of NSCLC patients with platinum-based chemotherapy, which might be associated with enhancement of its mRNA expression and the diminishment of activity. Identification of PARP1 T2285C polymorphism and mRNA expression may be the promising way for the individualised treatment of NSCLC.
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http://dx.doi.org/10.1093/mutage/geab022DOI Listing
August 2021

Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression.

Stroke 2021 Aug 10;52(9):2792-2801. Epub 2021 Jun 10.

Department of Cardiovascular Medicine (M.G., V.N., M.P., F.F., M.D.Y., A.L.), Mayo Clinic, Rochester, MN.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.032964DOI Listing
August 2021

Towards Uncovering the Intrinsic Data Structures for Unsupervised Domain Adaptation using Structurally Regularized Deep Clustering.

IEEE Trans Pattern Anal Mach Intell 2021 Jun 9;PP. Epub 2021 Jun 9.

Unsupervised domain adaptation (UDA) is to learn classification models that make predictions for unlabeled data on a target domain, given labeled data on a source domain whose distribution diverges from the target one. Mainstream UDA methods strive to learn domain-aligned features. Although impressive results have been achieved, these methods have a potential risk of damaging the intrinsic data structures of target discrimination, raising an issue of generalization particularly for UDA tasks in an inductive setting. To address this issue, we are motivated by a UDA assumption of structural similarity across domains, and propose to directly uncover the intrinsic target discrimination via constrained clustering, where we constrain the clustering solutions using structural source regularization that hinges on the very same assumption. Technically, we propose a hybrid model of Structurally Regularized Deep Clustering, which integrates the regularized discriminative clustering of target data with a generative one, and we thus term our method as H-SRDC. By enriching the structural similarity assumption, we extend H-SRDC for a pixel-level UDA task of semantic segmentation. We conduct extensive experiments on image classification and semantic segmentation. With no explicit feature alignment, our proposed H-SRDC outperforms all the existing methods under both the inductive and transductive settings.
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http://dx.doi.org/10.1109/TPAMI.2021.3087830DOI Listing
June 2021
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