Publications by authors named "Chao Tian"

217 Publications

Effects of sleep deprivation of various durations on novelty-related object recognition memory and object location memory in mice.

Behav Brain Res 2021 Oct 5:113621. Epub 2021 Oct 5.

Brain Research Center of Innovation Institute of Traditional Chinese medicine, Shandong University of traditional Chinese Medicine, Jinan, Shandong, China, 250355. Electronic address:

Sleep is essential for important physiological functions. Impairment of learning and memory function caused by lack of sleep is a common physiological phenomenon of which underlying changes in synaptic plasticity in the hippocampus are not well understood. The possible different effects of sleep deprivation (SD) lasting for various durations on learning and memory function and hippocampal synaptic plasticity are still not completely clear. In this study, we used a modified multiple platform method (MMPM) to induce rapid eye movement SD (REM SD), lasting for 24h, 48h, and 72h, separately. The novel place recognition (NPR) and novel object recognition (NOR) tasks were used to test the novelty-related object recognition memory (ORM) and object location memory (OLM) of mice. Then, hippocampal synaptic plasticity was evaluated after all behavioural experiments. The results showed that REM SD played a key role in OLM but not in ORM. Specifically, 24h REM SD improved novelty-related OLM, accompanied by a significantly increased hippocampal synaptic plasticity, including gain of dendritic spines, increased expression of hippocampal GluA1, and enhanced long-term potentiation (LTP), whereas 48h REM SD showed no effect on OLM or the hippocampal synaptic plasticity mentioned above; however, 72h REM SD impaired novelty-related OLM and weakened hippocampal synaptic plasticity, including serious loss of dendritic spines, decreased expression of hippocampal GluA1, and significantly attenuated LTP. Our results suggest that REM SD of various durations has different effects on both novelty-related OLM and hippocampal synaptic plasticity.
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http://dx.doi.org/10.1016/j.bbr.2021.113621DOI Listing
October 2021

The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study.

JAMA Psychiatry 2021 Sep 29. Epub 2021 Sep 29.

23andme, Inc, Sunnyvale, California.

Importance: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.

Objective: To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression.

Design, Setting, And Participants: Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021.

Exposures: Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts.

Main Outcomes And Measures: Depression status was defined based on health records and self-report questionnaires.

Results: There were a total of 194 548 study participants (approximate mean age, 51.3 years; 62.8% women). Participants included 15 771 individuals with depression and 178 777 control individuals of East Asian descent. Five novel associations were identified, including 1 in the meta-analysis for broad depression among those of East Asian descent: rs4656484 (β = -0.018, SE = 0.003, P = 4.43x10-8) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (β = 0.028, SE = 0.005, P = 6.48x10-9 for rs10240457). The lead variants of these 2 novel loci were not associated with depression risk in European ancestry cohorts (β = -0.003, SE = 0.005, P = .53 for rs4656484 and β = -0.005, SE = 0.004, P = .28 for rs10240457). Only 11% of depression loci previously identified in individuals of European descent reached nominal significance levels in the individuals of East Asian descent. The transancestry genetic correlation between cohorts of East Asian and European descent for clinical depression was r = 0.413 (SE = 0.159). Clinical depression risk was negatively genetically correlated with body mass index in individuals of East Asian descent (r = -0.212, SE = 0.084), contrary to findings for individuals of European descent.

Conclusions And Relevance: These results support caution against generalizing findings about depression risk factors across populations and highlight the need to increase the ancestral and geographic diversity of samples with consistent phenotyping.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.2099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482304PMC
September 2021

A Novel Synthetic Precursor of Styryl Sulfone Neuroprotective Agents Inhibits Neuroinflammatory Responses and Oxidative Stress Damage through the P38 Signaling Pathway in the Cell and Animal Model of Parkinson's Disease.

Molecules 2021 Sep 3;26(17). Epub 2021 Sep 3.

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

A novel class of styryl sulfones were designed and synthesized as CAPE derivatives by our work team, which showed a multi-target neuroprotective effect, including antioxidative and anti-neuroinflammatory properties. However, the underlying mechanisms remain unclear. In the present study, the anti-Parkinson's disease (PD) activity of 10 novel styryl sulfone compounds was screened by the cell viability test and the NO inhibition test in vitro. It was found that exhibited the highest activity against PD among them. In a MPTP-induced mouse model of PD, the biological activity of was validated through suppressing dopamine neurotoxicity, microglial activation, and astrocytes activation. With compound , we conducted the mechanistic studies about anti-inflammatory responses through inhibition of p38 phosphorylation to protect dopaminergic neurons, and antioxidant effects through promoting nuclear factor erythroid 2-related factor 2 (Nrf2). The results revealed that could significantly inhibit 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP)-induced p38 mitogen-activated protein kinase (MAPK) activation in both in vitro and in vivo PD models, thus inhibiting the NF-κB-mediated neuroinflammation-related apoptosis pathway. Simultaneously, it could promote Nrf2 nuclear transfer, and upregulate the expression of antioxidant phase II detoxification enzymes HO-1 and GCLC, and then reduce oxidative damage.
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http://dx.doi.org/10.3390/molecules26175371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433997PMC
September 2021

Influence of the shallow groundwater table on the groundwater NO and direct NO emissions in summer maize field in the North China Plain.

Sci Total Environ 2021 Dec 5;799:149495. Epub 2021 Aug 5.

Key Laboratory of Ecosystem Network Observation and Modeling, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100190, China. Electronic address:

Agriculture is an important NO emissions source. Water cycle and nitrogen cycles have important effects on NO in farmland ecosystems. The changes in the groundwater table can lead to changes in farmland the water and nitrogen cycle processes. However, how this such changes will affect N2O emissions from farmland remains unclear. In this study, a two-year volume lysimeter experiment (2019-2020), including four controlled groundwater tables (i.e., 40, 70, 110, and 150 cm), was performed to monitor the variations in the NO and NO concentrations in shallow groundwater as well as the direct NO emissions due to surface soil and groundwater evaporation. Our results showed that NO emissions during fertilization accounted for 80%-90% of the total NO emissions throughout the maize growing period. Direct NO emissions increase with the increase in the groundwater table. The total NO emissions in 2020 were 96.44, 9.75, 6.46, and 6.22 kg ha y at a groundwater table of 40, 70, 110, and 150 cm, respectively. The high water-filled pore space (WFPS) value resulting from the elevated groundwater table increased the groundwater-atmosphere connectivity, leading to significantly increased NO emissions after fertilization. Increased precipitation (454.90 mm in 2020 vs. 180.30 mm in 2019) accelerated the hydrological processes in agroecology, reducing the retention time of NO (6 weeks in 2020 vs. 7.5 weeks in 2019) and NO (6.75 weeks in 2020 vs. 7.25 weeks in 2019) in shallow groundwater. Studying the influence of shallow groundwater tables on direct NO emissions will provide insights into the interaction between the water and nitrogen cycles in agroecosystems. The results of this study suggest that direct NO emissions can be effectively reduced by controlling the groundwater table in agricultural fields in the North China Plain.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149495DOI Listing
December 2021

Role of acetylation in doxorubicin-induced cardiotoxicity.

Redox Biol 2021 Oct 31;46:102089. Epub 2021 Jul 31.

Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; Department of Cardiology, The Affiliated Cardiovascular Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266071, China. Electronic address:

As a potent chemotherapeutic agent, doxorubicin (DOX) is widely used for the treatment of a variety of cancers However, its clinical utility is limited by dose-dependent cardiotoxicity, and pathogenesis has traditionally been attributed to the formation of reactive oxygen species (ROS). Accordingly, the prevention of DOX-induced cardiotoxicity is an indispensable goal to optimize therapeutic regimens and reduce morbidity. Acetylation is an emerging and important epigenetic modification regulated by histone deacetylases (HDACs) and histone acetyltransferases (HATs). Despite extensive studies of the molecular basis and biological functions of acetylation, the application of acetylation as a therapeutic target for cardiotoxicity is in the initial stage, and further studies are required to clarify the complex acetylation network and improve the clinical management of cardiotoxicity. In this review, we summarize the pivotal functions of HDACs and HATs in DOX-induced oxidative stress, the underlying mechanisms, the contributions of noncoding RNAs (ncRNAs) and exercise-mediated deacetylases to cardiotoxicity. Furthermore, we describe research progress related to several important SIRT activators and HDAC inhibitors with potential clinical value for chemotherapy and cardiotoxicity. Collectively, a comprehensive understanding of specific roles and recent developments of acetylation in doxorubicin-induced cardiotoxicity will provide a basis for improved treatment outcomes in cancer and cardiovascular diseases.
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http://dx.doi.org/10.1016/j.redox.2021.102089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350499PMC
October 2021

FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression.

Commun Biol 2021 07 2;4(1):832. Epub 2021 Jul 2.

Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Singapore, Singapore.

Sialyl-Lewis x (sLe, CD15s) is a tetra-saccharide on the surface of leukocytes required for E-selectin-mediated rolling, a prerequisite for leukocytes to migrate out of the blood vessels. Here we show using flow cytometry that sLe expression on basophils and mast cell progenitors depends on fucosyltransferase 6 (FUT6). Using genetic association data analysis and qPCR, the cell type-specific defect was associated with single nucleotide polymorphisms (SNPs) in the FUT6 gene region (tagged by rs17855739 and rs778798), affecting coding sequence and/or expression level of the mRNA. Heterozygous individuals with one functional FUT6 gene harbor a mixed population of sLe and sLe basophils, a phenomenon caused by random monoallelic expression (RME). Microfluidic assay demonstrated FUT6-deficient basophils rolling on E-selectin is severely impaired. FUT6 null alleles carriers exhibit elevated blood basophil counts and a reduced itch sensitivity against insect bites. FUT6-deficiency thus dampens the basophil-mediated allergic response in the periphery, evident also in lower IgE titers and reduced eosinophil counts.
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http://dx.doi.org/10.1038/s42003-021-02295-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253766PMC
July 2021

Enhanced anti-tumor response elicited by a novel oncolytic HSV-1 engineered with an anti-PD-1 antibody.

Cancer Lett 2021 Oct 15;518:49-58. Epub 2021 Jun 15.

School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China; Beijing WellGene Company Ltd., Beijing, 100085, China. Electronic address:

Oncolytic viruses as cancer vaccines modulate the tumor microenvironment and act synergistically with immune checkpoint inhibitors to overcome resistance. Taking advantage of the loading capacity for exogenous genes, we generated a recombinant herpes simplex virus type 1 (HSV-1), HSV-aPD-1, carrying a full-length humanized anti-PD-1 monoclonal antibody (anti-PD-1 mAb) that replicates and expresses anti-PD-1 mAbs in tumor cells in vitro and in vivo. Its anti-tumor effect was assessed in human PD-1 knock-in mice by analyzing tumor inhibition, cell populations and RNA expression in tumors, and serum cytokine levels. Enhanced anti-tumor immune responses and T-cell infiltration were induced by HSV-aPD-1 compared with unloaded virus or anti-PD-1 therapy in both MC38 and B16-F10 models, resulting in improved treatment efficacy in the latter. Moreover, compared with unloaded HSV-1 or HSV-1 loaded with GM-CSF/IL-2 combined with anti-PD-1 mAbs, HSV-aPD-1 displayed similar therapeutic control of tumor growth. Finally, tumor RNAseq analysis in the B16-F10 model showed upregulated IFN pathway and antigen processing and presentation genes, and downregulated angiogenesis and cell adhesion genes, which all contribute to tumor inhibition. These findings indicate the clinical potential of HSV-aPD-1 as monotherapy or combination therapy, especially in tumors resistant to immune checkpoint inhibitors.
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http://dx.doi.org/10.1016/j.canlet.2021.06.005DOI Listing
October 2021

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms.

World J Gastroenterol 2021 Jun;27(21):2895-2909

Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China.

Background: Poorly differentiated gastric neuroendocrine neoplasms (PDGNENs) include gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma, which are highly malignant and rare tumors, and their incidence has increased over the past few decades. However, the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.

Aim: To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs

Methods: The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.

Results: Among the 232 patients with PDGNENs, 191 (82.3%) were male, with an average age of 62.83 ± 9.11 years. One hundred and thirteen (49.34%) of 229 patients had a stage III disease and 86 (37.55%) had stage IV disease. Three (1.58%) of 190 patients had no clinical symptoms, while 187 (98.42%) patients presented clinical symptoms. The tumors were mainly (89.17%) solitary and located in the upper third of the stomach (cardia and fundus of stomach: 115/215, 53.49%). Most lesions were ulcers (157/232, 67.67%), with an average diameter of 4.66 ± 2.77 cm. In terms of tumor invasion, the majority of tumors invaded the serosa (116/198, 58.58%). The median survival time of the 232 patients was 13.50 mo (7, 31 mo), and the overall 1-year, 3-year, and 5-year survival rates were 49%, 19%, and 5%, respectively. According to univariate analysis, tumor number, tumor diameter, gastric invasion status, American Joint Committee on Cancer (AJCC) stage, and distant metastasis status were prognostic factors for patients with PDGNENs. Multivariate analysis showed that tumor number, tumor diameter, AJCC stage, and distant metastasis status were independent prognostic factors for patients with PDGNENs.

Conclusion: The overall prognosis of patients with PDGNENs is poor. The outcomes of patients with a tumor diameter > 5 cm, multiple tumors, and stage IV tumors are worse than those of other patients.
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http://dx.doi.org/10.3748/wjg.v27.i21.2895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173377PMC
June 2021

Agricultural impacts drive longitudinal variations of riverine water quality of the Aral Sea basin (Amu Darya and Syr Darya Rivers), Central Asia.

Environ Pollut 2021 Sep 19;284:117405. Epub 2021 May 19.

Tashkent Institute of Irrigation and Agricultural Mechanization Engineers, Tashkent, 100000, Uzbekistan.

River ecosystems are under increasing stress in the background of global change and ever-growing anthropogenic impacts in Central Asia. However, available water quality data in this region are insufficient for a reliable assessment of the current status, which come as no surprise that the limited knowledge of regulating processes for further prediction of solute variations hinders the development of sustainable management strategies. Here, we analyzed a dataset of various water quality variables from two sampling campaigns in 2019 in the catchments of two major rivers in Central Asia-the Amu Darya and Syr Darya Rivers. Our results suggested high spatial heterogeneity of salinity and major ion components along the longitudinal directions in both river catchments, pointing to an increasing influence of human activities toward downstream areas. We linked the modeling outputs from the global nutrient model (IMAGE-GNM) to riverine nutrients to elucidate the effect of different natural and anthropogenic sources in dictating the longitudinal variations of the riverine nutrient concentrations (N and P). Diffuse nutrient loadings dominated the export flux into the rivers, whereas leaching and surface runoff constituted the major fractions for N and P, respectively. Discharge of agricultural irrigation water into the rivers was the major cause of the increases in nutrients and salinity. Given that the conditions in Central Asia are highly susceptible to climate change, our findings call for more efforts to establish holistic management of water quality.
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http://dx.doi.org/10.1016/j.envpol.2021.117405DOI Listing
September 2021

A Novel Nomogram for Individually Predicting of Vascular Invasion in Gastric Cancer.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211004924

Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.

Purpose: Vascular invasion (VI) is associated with recurrence and is an indicator of poor prognosis in gastric cancer (GC). Pre-operative identification of VI may guide the selection of the optimal surgical approach and assess the requirement for neoadjuvant therapy.

Methods: A total of 271 patients were retrospectively collected and randomly allocated into the training and validation datasets. The least absolute shrinkage and selection operator regression model was used to select potentially relevant features, and multivariable logistic regression analysis was used to develop the nomogram.

Results: The nomogram consisted of pre-operative serum complement C3 levels, duration of symptoms, pre-operative computed tomography stage, abdominal distension and undifferentiated carcinoma. The nomogram provided good calibration for both the training and the validation set, with area under the curve values of 0.792 and 0.774. Decision curve analysis revealed that the nomogram was clinically useful.

Conclusion: The present study constructed a nomogram for the pre-operative prediction of VI in patients with GC. The nomogram may aid the identification of high-risk patients and aid the optimization of pre-operative decision-making.
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http://dx.doi.org/10.1177/15330338211004924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111553PMC
April 2021

Correction to: Recent developments in photoacoustic imaging and sensing for nondestructive testing and evaluation.

Vis Comput Ind Biomed Art 2021 Apr 29;4(1):10. Epub 2021 Apr 29.

Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, 230026, Anhui, China.

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http://dx.doi.org/10.1186/s42492-021-00077-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085174PMC
April 2021

Potential of exosomes as diagnostic biomarkers and therapeutic carriers for doxorubicin-induced cardiotoxicity.

Int J Biol Sci 2021 27;17(5):1328-1338. Epub 2021 Mar 27.

Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.

Doxorubicin (DOX) is a kind of representative anthracyclines. It has greatly prolonged lifespan of cancer patients. However, a long course of DOX chemotherapy could induce various forms of deaths of cardiomyocytes, such as apoptosis, pyroptosis and ferroptosis, contributing to varieties of cardiac complications called cardiotoxicity. It has become a major concern considering the large number of cancer patients' worldwide and increased survival rates after chemotherapy. Exosomes, a subgroup of extracellular vesicles (EVs), are secreted by nearly all cells and consist of lipid bilayers, nucleic acids and proteins. They can serve as mediators between intercellular communication via the transfer of bioactive molecules from secretory to recipient cells, modulating multiple pathophysiological processes. It has been proven that exosomes in body fluids can serve as biomarkers for doxorubicin-induced cardiotoxicity (DIC). Moreover, exosomes have attracted considerable attention because of their capacity as carriers of certain proteins, genetic materials (miRNA and lncRNA), and chemotherapeutic drugs to decrease the dosage of DOX and alleviate cardiotoxicity. This review briefly describes the characteristics of exosomes and highlights their clinical application potential as diagnostic biomarkers and drug delivery vehicles for DIC, thus providing a strategy for addressing it based on exosomes.
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http://dx.doi.org/10.7150/ijbs.58786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040474PMC
March 2021

The Molecular Mechanisms of Cardiotoxicity Induced by HER2, VEGF, and Tyrosine Kinase Inhibitors: an Updated Review.

Cardiovasc Drugs Ther 2021 Apr 13. Epub 2021 Apr 13.

Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266100, Shandong, China.

Aim: In recent decades, there has been a revolutionary decrease in cancer-related mortality and an increase in survival due to the introduction of novel targeted drugs. Nevertheless, drugs targeting human epidermal growth factor receptor 2 (HER-2), angiogenesis, and other tyrosine kinases also come with unexpected cardiac side effects, including heart failure, hypertension, arterial thrombosis, and arrhythmias, and have mechanisms that are unlike those of classic chemotherapeutic agents. In addition, it is challenging to address some problems, as the existing guidelines need to be more specific, and further large-scale clinical trials and experimental studies are required to confirm the benefit of administering cardioprotective agents to patients treated with targeted therapies. Therefore, an improved understanding of cardiotoxicity becomes increasingly important to minimize the pernicious effects and maximize the beneficial effects of targeted agents.

Methods: "Cardiotoxicity", "targeted drugs", "HER2", "trastuzumab", "angiogenesis inhibitor", "VEGF inhibitor" and "tyrosine kinase inhibitors" are used as keywords for article searches.

Results: In this article, we report several targeted therapies that induce cardiotoxicity and update knowledge of the clinical evidence, molecular mechanisms, and management measures.
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http://dx.doi.org/10.1007/s10557-021-07181-3DOI Listing
April 2021

Distinct clinical phenotypes for Crohn's disease derived from patient surveys.

BMC Gastroenterol 2021 Apr 9;21(1):160. Epub 2021 Apr 9.

Department of Bioengineering, Stanford University, Shriram Room 209, MC: 4245, 443 Via Ortega Drive, Stanford, CA, 94305-4145, USA.

Background: Defining clinical phenotypes provides opportunities for new diagnostics and may provide insights into early intervention and disease prevention. There is increasing evidence that patient-derived health data may contain information that complements traditional methods of clinical phenotyping. The utility of these data for defining meaningful phenotypic groups is of great interest because social media and online resources make it possible to query large cohorts of patients with health conditions.

Methods: We evaluated the degree to which patient-reported categorical data is useful for discovering subclinical phenotypes and evaluated its utility for discovering new measures of disease severity, treatment response and genetic architecture. Specifically, we examined the responses of 1961 patients with inflammatory bowel disease to questionnaires in search of sub-phenotypes. We applied machine learning methods to identify novel subtypes of Crohn's disease and studied their associations with drug responses.

Results: Using the patients' self-reported information, we identified two subpopulations of Crohn's disease; these subpopulations differ in disease severity, associations with smoking, and genetic transmission patterns. We also identified distinct features of drug response for the two Crohn's disease subtypes. These subtypes show a trend towards differential genotype signatures.

Conclusion: Our findings suggest that patient-defined data can have unplanned utility for defining disease subtypes and may be useful for guiding treatment approaches.
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http://dx.doi.org/10.1186/s12876-021-01740-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034169PMC
April 2021

MicroRNA-302c-3p inhibits endothelial cell pyroptosis via directly targeting NOD-, LRR- and pyrin domain-containing protein 3 in atherosclerosis.

J Cell Mol Med 2021 05 30;25(9):4373-4386. Epub 2021 Mar 30.

Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Inflammation and endothelial dysfunction are important participants and drivers in atherosclerosis. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and the resulting pyroptosis are involved in the initiation and vicious circle of chronic inflammation, thus playing an indispensable role in atherosclerosis. Accordingly, blocking the activation of NLRP3 inflammasome may be a promising treatment strategy to blunt the progression of atherosclerosis. In this study, it was demonstrated that miR-302c-3p exerted anti-pyroptosis effects by directly targeting NLRP3 in vivo and in vitro. In brief, the expression of miR-302c-3p was down-regulated whereas the expression of NLRP3 was up-regulated in human plaques and in vitro pyroptosis model of endothelial cells. Overexpression of miR-302c-3p suppressed endothelial cell pyroptosis by targeting specific sites of NLRP3. By comparison, down-regulation of endogenous miR-302c-3p led to the opposite results, which were reversed by silencing the expression of NLRP3. Finally, the up-regulation of miR-302c-3p inhibited the inflammation and pyroptosis of atherosclerosis mouse model. In conclusion, miR-302c-3p may be a powerful and attractive target for suppressing endothelial inflammation and pyroptosis, providing a novel strategy for preventing or alleviating the progression of atherosclerosis.
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http://dx.doi.org/10.1111/jcmm.16500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093969PMC
May 2021

Quality assessment of clinical guidelines on probiotics therapy in children with IBD using the AGREE II instrument.

J Clin Pharm Ther 2021 Aug 25;46(4):1155-1165. Epub 2021 Mar 25.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

What Is Known And Objective: The morbidity of inflammatory bowel disease (IBD) in children has significantly increased in recent years. The diagnosis and treatment of IBD in children are progressing rapidly. Probiotics have been extensively studied in a variety of gastrointestinal diseases. However, the effectiveness of probiotics for IBD is inconsistent. This study summarized the recommendations on using probiotics from high-quality guidelines, and the recommendations may assist clinicians in the treatment of paediatric IBD.

Methods: Guidelines were identified by searching PubMed, EMBASE, three Chinese literature databases and websites of relevant institutions. Guidelines that addressed the treatments of paediatric IBD in Chinese and English were included and evaluated with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument to assess methodological quality. The levels of recommendation were also evaluated, and finally, the recommendations of probiotics application in IBD were summarized.

Results And Discussion: A total of 14 guidelines that met inclusion criteria were identified and evaluated, and 12 of them were evidence-based (EB) guidelines, and the other two guidelines were developed by consensus. The mean percentages for the AGREE II domain scores were as follows: "Scope and purpose" 97.22%, "Clarity of presentation" 93.78%, "Applicability" 55.85%, "Editorial independence" 59.92%, "Stakeholder involvement" 74.34%, and "Rigor of development" 71.58%. Three guidelines received the Grade A-"Strongly recommended," the rest of the guidelines received a B grade-"Recommended with modifications" in the overall assessment.

What Is New And Conclusion: The overall quality of the guidelines on IBD management in children was high. Conversely, the fundamental recommendations on the application of probiotics in the treatment of IBD varied. For instance, the recommendations of probiotics on Crohn's disease (CD) were not available by any of the analysed guidelines, the recommendations of utilizing probiotics in treating ulcerative colitis (UC) were not uniform as several guidelines considered using VSL#3 or Escherichia coli Nissle 1917 for the treatment.
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http://dx.doi.org/10.1111/jcpt.13422DOI Listing
August 2021

Review recent developments in photoacoustic imaging and sensing for nondestructive testing and evaluation.

Vis Comput Ind Biomed Art 2021 Mar 19;4(1). Epub 2021 Mar 19.

Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, 230026, Hefei, Anhui, China.

Photoacoustic (PA) imaging has been widely used in biomedical research and preclinical studies during the past two decades. It has also been explored for nondestructive testing and evaluation (NDT/E) and for industrial applications. This paper describes the basic principles of PA technology for NDT/E and its applications in recent years. PA technology for NDT/E includes the use of a modulated continuous-wave laser and a pulsed laser for PA wave excitation, PA-generated ultrasonic waves, and all-optical PA wave excitation and detection. PA technology for NDT/E has demonstrated broad applications, including the imaging of railway cracks and defects, the imaging of Li metal batteries, the measurements of the porosity and Young's modulus, the detection of defects and damage in silicon wafers, and a visualization of underdrawings in paintings.
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http://dx.doi.org/10.1186/s42492-021-00073-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979856PMC
March 2021

Generation of UCiPSC-derived neurospheres for cell therapy and its application.

Stem Cell Res Ther 2021 03 18;12(1):188. Epub 2021 Mar 18.

CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.

Background: Neural stem cell (NSC) therapy remains one of the most potential approaches for the treatment of neurological disorders. The discovery of human induced pluripotent stem cells (hiPSCs) and the establishment of hiPSC-derived human neural stem cells (hiNSCs) have revolutionized the technique of cell therapy. Meanwhile, it is often required that NSCs are stored and transported to a long distance for research or treatment purposes. Although high survival rates could be maintained, conventional methods for cell transportation (dry ice or liquid nitrogen) are inconvenient and expensive. Therefore, the establishment of a safe, affordable, and low-cost strategy to store and transport easily accessible hiPSCs and hiNSCs, with characteristics that match fetal hNSCs, is incredibly urgent.

Methods: We reprogrammed human urinary cells to iPSCs using a non-integrating, virus-free technique and differentiated the iPSCs toward iNSCs/neurospheres and neurons, under Good Manufacturing Practice (GMP)-compatible conditions. The pluripotency of iPSCs and iNSCs was characterized by a series of classical methods (surface markers, karyotype analysis, and in vitro as well as in vivo differentiation capabilities, etc.).

Results: Here, our results showed that we successfully generated hiNSCs/neurospheres from more available, non-invasive, and more acceptable urinary cells by a virus-free technique. Next, we demonstrated that the iNSCs differentiated into mature cerebral cortical neurons and neural networks. Interestingly, hiNSCs survived longer as neurospheres at ambient temperature (AT) than those cultured in a monolayer. Within 7 days approximately, the neural viability remained at > 80%, while hiNSCs cultured in a monolayer died almost immediately. Neurospheres exposed to AT that were placed under standard culture conditions (37 °C, 5% CO) recovered their typical morphology, and retained their proliferation and differentiation abilities.

Conclusions: In this study, we provided a simple method for the storage of NSCs as neurospheres at AT as an alternative method to more costly and inconvenient traditional methods of cryopreservation. This will enable hiNSCs to be transported over long distances at AT and facilitate the therapeutic application of NSCs as neurospheres without any further treatment.
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http://dx.doi.org/10.1186/s13287-021-02238-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977190PMC
March 2021

Nuclear genome-wide associations with mitochondrial heteroplasmy.

Sci Adv 2021 Mar 17;7(12). Epub 2021 Mar 17.

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

The role of the nuclear genome in maintaining the stability of the mitochondrial genome (mtDNA) is incompletely known. mtDNA sequence variants can exist in a state of heteroplasmy, which denotes the coexistence of organellar genomes with different sequences. Heteroplasmic variants that impair mitochondrial capacity cause disease, and the state of heteroplasmy itself is deleterious. However, mitochondrial heteroplasmy may provide an intermediate state in the emergence of novel mitochondrial haplogroups. We used genome-wide genotyping data from 982,072 European ancestry individuals to evaluate variation in mitochondrial heteroplasmy and to identify the regions of the nuclear genome that affect it. Age, sex, and mitochondrial haplogroup were associated with the extent of heteroplasmy. GWAS identified 20 loci for heteroplasmy that exceeded genome-wide significance. This included a region overlapping mitochondrial transcription factor A (), which has multiple roles in mtDNA packaging, replication, and transcription. These results show that mitochondrial heteroplasmy has a heritable nuclear component.
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http://dx.doi.org/10.1126/sciadv.abe7520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968846PMC
March 2021

Research in porous structure of cellulose aerogel made from cellulose nanofibrils.

Int J Biol Macromol 2021 Mar 14;172:573-579. Epub 2021 Jan 14.

China National Pulp and Paper Research Institute Co., Ltd., Beijing, China; National Engineering Laboratory for Pulp and Paper, Beijing, China. Electronic address:

In this study, a simple strategy to fabricate the cellulose aerogel with homogeneous porous structure and good compression strength properties has been demonstrated. The cellulose aerogel was simply prepared by adding styrene acrylic emulsion (SAE) to the TEMPO-oxidized cellulose nanofibrils (CNF), followed by freeze-drying and oven-heating, in which covalent bond between CNF and SAE was confirmed by FT-IR. Meanwhile, the regulation process of porous structure of cellulose aerogels was investigated by varying the properties of CNF, and the addition of carboxymethyl cellulose (CMC) and SAE. The results demonstrated that the porous structure of cellulose aerogel was gradually improved with increasing carboxyl content of CNF. CMC could effectively increase in specific surface area of cellulose aerogel, achieving a more preferred porous structure due to the elimination of hornification. SAE could highly enhance the uniformity of structure with specific surface area up to 184 m/g, porosity up to 99%, and successfully improve the strength properties, showing the fabricated cellulose aerogel as a potential cushion packaging material.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.080DOI Listing
March 2021

Spatial Resolution in Photoacoustic Computed Tomography.

Rep Prog Phys 2021 Jan 12. Epub 2021 Jan 12.

University of Science and Technology of China, Hefei, 230026, CHINA.

Photoacoustic computed tomography (PACT) is a novel biomedical imaging modality and has experienced fast developments in the past two decades. Spatial resolution is an important criterion to measure the imaging performance of a PACT system. Here we survey state-of-the-art literature on the spatial resolution of PACT and analyze resolution degradation models from signal generation, propagation, reception, to image reconstruction. Particularly, the impacts of laser pulse duration, acoustic attenuation, acoustic heterogeneity, detector bandwidth, detector aperture, detector view angle, discrete sampling, and image reconstruction algorithms are reviewed and discussed. Analytical expressions of point spread functions related to these impacting factors are summarized based on rigorous mathematical formulas. State-of-the-art approaches devoted to enhancing spatial resolution are also reviewed. This work is expected to elucidate the concept of spatial resolution in PACT and inspire novel image quality enhancement techniques.
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http://dx.doi.org/10.1088/1361-6633/abdab9DOI Listing
January 2021

Influence of land use and change in the proportion of electron donors required for denitrification on NO in groundwater.

Environ Sci Pollut Res Int 2021 Apr 5;28(14):17684-17696. Epub 2021 Jan 5.

State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing, 100875, China.

Nitrate (NO) and nitrous oxide (NO) accumulate in groundwater in relation to human activities and pose multiple threats to the global environment (harming human health and atmospheric damage). This study focused on the evaluation of groundwater NO, NO, and its indirect emission factor under different land use types (agricultural land, urban land, and forest) and response mechanism of major anions to dissolved NO within groundwater in Dexing which has the largest copper mine in Asia. Specifically, this work used self-organizing maps (SOMs) to identify which anion conditions (NO, SO, F, Cl) and water quality parameters were suitable for the accumulation of groundwater NO. Finally, we found that the shallow groundwater of agricultural land has a high concentration of NO and NO and the agricultural activity has a significant effect on the temporal and spatial variation of NO in groundwater. The result of SOMs combined with the positive correlation between NO and NO/SO suggested that the electron donor required for denitrification has a significant effect on NO accumulation. In this respect, when an increased proportion of reduced sulfur is available as an electron donor for autotrophic denitrification, this results in lower concentrations of NO in groundwater. Through the comprehensive evaluation of the anion conditions and NO in groundwater under different land use types, this study case can help to estimate the NO indirect emission from groundwater, so as to constrain the global nitrogen budget.
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http://dx.doi.org/10.1007/s11356-020-12258-xDOI Listing
April 2021

Meta-analysis of prognostic factors for recurrence of resected well-differentiated pancreatic neuroendocrine tumors.

Neuroendocrinology 2020 Dec 28. Epub 2020 Dec 28.

Well-differentiated pancreatic neuroendocrine tumors (WDPNETs) are a group of rare and heterogeneous tumors. However, the prognostic factors for recurrence after curative resection still remain controversial. We aim to illustrate the prognostic factors for recurrence of resected WDPNETs. All relevant articles published through June 2020 were identified via PubMed, Embase, Web of Science and the Cochrane Library. Articles that examined the prognostic factors of WDPNETs were enrolled. 10 articles were finally included in this study. From 1993 to 2018, 2863 patients underwent curative resection and 358 patients had recurrence, the combined recurrence rate was 13%. Furthermore, the pooled data indicated that patients with G2, positive lymph node and surgical resection margin, vascular invasion and perineural invasion had a decreased disease free survival for WDPNETs. However, gender, function, and tumor size had no significant relationship with WDPNETs recurrence. These findings demonstrated that G2, positive lymph node and surgical resection margin, vascular invasion and perineural invasion could be prognostic factors for recurrence of resected WDPNETs, indicating that patients with these high-risk factors need closer postoperative follow-up, and may benefit from adjuvant therapy.
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http://dx.doi.org/10.1159/000514047DOI Listing
December 2020

A semi-analytical algorithm for deriving the particle size distribution slope of turbid inland water based on OLCI data: A case study in Lake Hongze.

Environ Pollut 2021 Feb 11;270:116288. Epub 2020 Dec 11.

Department of Earth Sciences, Indiana University-Purdue University Indianapolis (IUPUI), IN, 46202, USA.

The particle size distribution (PSD) slope (ξ) can indicate the predominant particle size, material composition, and inherent optical properties (IOPs) of inland waters. However, few semi-analytical methods have been proposed for deriving ξ from the surface remote sensing reflectance due to the variable optical state of inland waters. A semi-analytical algorithm was developed for inland waters having a wide range of turbidity and ξ in this study. Application of the proposed model to Ocean and Land Color Instrument (OLCI) imagery of the water body resulted in several important observations: (1) the proposed algorithm (754 nm and 779 nm combination) was capable of retrieving ξ with R2 being 0.72 (p < 0.01, n = 60), and MAPE and RMSE being 4.37% and 0.22 (n = 30) respectively; (2) the ξ in HZL was lower in summer than other seasons during the period considered, this variation was driven by the phenological cycle of algae and the runoff caused by rainfall; (3) the band optimization proposed in this study is important for calculating the particle backscattering slope (η) and deriving ξ because it is feasible for both algae dominant and sediment governed turbid inland lakes. These observations help improve our understanding of the relationship between IOPs and ξ, which are affected by different bio-optic processes and algal phenology in the lake environment.
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http://dx.doi.org/10.1016/j.envpol.2020.116288DOI Listing
February 2021

Correlation Between Anatomic Variations of Sphenoid Sinuses and Pituitary Adenoma.

J Craniofac Surg 2021 Jul-Aug 01;32(5):1685-1688

Department of Neurosurgery, Tianjin Huanhu Hospital.

Background: Many persons have studied relationship between anatomic variations (AVs) of sphenoid sinuses (SS) and paranasal disease, but no research has been done to reveal the correlation between AVs of SS and sellar region lesions.

Objective: To compare AVs of SS between sellar region lesions and healthy persons and analyze factors affecting the volume of SS and explore the correlation between AVs of SS and pituitary adenomas (PAs).

Methods: Clinical data of 53 PAs as experiment group and 30 healthy persons as control team was reviewed. Computed tomography images of SS performed at Tianjin Huanhu Hospital were studied. The AVs of SS including degree of pneumatization, type of intersinus septum (IS), and volume of SS were evaluated by ITK-SNAP software.

Results: Age, gender, degree of pneumatization, and type of IS had no significant difference between groups, while the volume of SS in experiment group was smaller than that in control group (P < 0.05). The volume of SS was associated with age, sex, degree of pneumatization, type of IS in control group, and degree of pneumatization, type of IS in experiment group. In experiment group, patients with postoperative pathological examination ki67 ≥ 3% had bigger volume and higher recurrent rate (P < 0.05).

Conclusion: Visualizing different orientations and 3D model of SS is conducive to the success of trans-sphenoid surgery. Pituitary adenomas can deform the SS leading to smaller volume. The volume of SS can be a factor used to predict the outcome of PAs.
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http://dx.doi.org/10.1097/SCS.0000000000007293DOI Listing
July 2021

Lymphatic Flow: A Potential Target in Sepsis-Associated Acute Lung Injury.

J Inflamm Res 2020 23;13:961-968. Epub 2020 Nov 23.

Department of Anaesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.

Sepsis is life-threatening organ dysfunction caused by an imbalance in the body's response to infection and acute lung injury (ALI) related to sepsis is a common complication. The rapid morbidity and high mortality associated with sepsis is a significant clinical problem facing critical care medicine. Inflammation plays a vital role in the occurrence of sepsis. Notably, the body produces different immune cells and pro-inflammatory factors to clear pathogens. However, excessive inflammation can damage multiple tissues and organs when it fails to resolve in time. Additionally, lymphatic vessels could effectively transfer inflammatory cells and factors away from tissues and into blood circulation, thereby reducing damage, and promoting the resolution of inflammation. Therefore, any dysfunction and/or destruction of the lymphatic system may result in lymphedema followed by inflammatory storms and eventual sepsis. Consequently, the present study aimed to review and highlight the role of lymphatic vessels in related body tissues and organs during sepsis and other associated diseases.
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http://dx.doi.org/10.2147/JIR.S284090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695606PMC
November 2020

The association of clinical phenotypes to known AD/FTD genetic risk loci and their inter-relationship.

PLoS One 2020 5;15(11):e0241552. Epub 2020 Nov 5.

Johnson & Johnson Innovation, South San Francisco, CA, United States of America.

To elucidate how variants in genetic risk loci previously implicated in Alzheimer's Disease (AD) and/or frontotemporal dementia (FTD) contribute to expression of disease phenotypes, a phenome-wide association study was performed in two waves. In the first wave, we explored clinical traits associated with thirteen genetic variants previously reported to be linked to disease risk using both the 23andMe and UKB cohorts. We tested 30 additional AD variants in UKB cohort only in the second wave. APOE variants defining ε2/ε3/ε4 alleles and rs646776 were identified to be significantly associated with metabolic/cardiovascular and longevity traits. APOE variants were also significantly associated with neurological traits. ABI3 variant rs28394864 was significantly associated with cardiovascular (e.g. (hypertension, ischemic heart disease, coronary atherosclerosis, angina) and immune-related trait asthma. Both APOE variants and CLU variant were significantly associated with nearsightedness. HLA- DRB1 variant was associated with diseases with immune-related traits. Additionally, variants from 10+ AD genes (BZRAP1-AS1, ADAMTS4, ADAM10, APH1B, SCIMP, ABI3, SPPL2A, ZNF232, GRN, CD2AP, and CD33) were associated with hematological measurements such as white blood cell (leukocyte) count, monocyte count, neutrophill count, platelet count, and/or mean platelet (thrombocyte) volume (an autoimmune disease biomarker). Many of these genes are expressed specifically in microglia. The associations of ABI3 variant with cardiovascular and immune-related traits are one of the novel findings from this study. Taken together, it is evidenced that at least some AD and FTD variants are associated with multiple clinical phenotypes and not just dementia. These findings were discussed in the context of causal relationship versus pleiotropy via Mendelian randomization analysis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241552PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644002PMC
December 2020

Genome-wide association studies of antidepressant class response and treatment-resistant depression.

Transl Psychiatry 2020 10 26;10(1):360. Epub 2020 Oct 26.

23andMe, Inc., Sunnyvale, CA, USA.

The "antidepressant efficacy" survey (AES) was deployed to > 50,000 23andMe, Inc. research participants to investigate the genetic basis of treatment-resistant depression (TRD) and non-treatment-resistant depression (NTRD). Genome-wide association studies (GWAS) were performed, including TRD vs. NTRD, selective serotonin reuptake inhibitor (SSRI) responders vs. non-responders, serotonin-norepinephrine reuptake inhibitor (SNRI) responders vs. non-responders, and norepinephrine-dopamine reuptake inhibitor responders vs. non-responders. Only the SSRI association reached the genome-wide significance threshold (p < 5 × 10): one genomic region in RNF219-AS1 (SNP rs4884091, p = 2.42 × 10, OR = 1.21); this association was also observed in the meta-analysis (13,130 responders vs. 6,610 non-responders) of AES and an earlier "antidepressant efficacy and side effects" survey (AESES) cohort. Meta-analysis for SNRI response phenotype derived from AES and AESES (4030 responders vs. 3049 non-responders) identified another genomic region (lead SNP rs4955665, p = 1.62 × 10, OR = 1.25) in an intronic region of MECOM passing the genome-wide significance threshold. Meta-analysis for the TRD phenotype (31,068 NTRD vs 5,714 TRD) identified one additional genomic region (lead SNP rs150245813, p = 8.07 × 10, OR = 0.80) in 10p11.1 passing the genome-wide significance threshold. A stronger association for rs150245813 was observed in current study (p = 7.35 × 10, OR = 0.79) than the previous study (p = 1.40 × 10, OR = 0.81), and for rs4955665, a stronger association in previous study (p = 1.21 × 10, OR = 1.27) than the current study (p = 2.64 × 10, OR = 1.21). In total, three novel loci associated with SSRI or SNRI (responders vs. non-responders), and NTRD vs TRD were identified; gene level association and gene set enrichment analyses implicate enrichment of genes involved in immune process.
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http://dx.doi.org/10.1038/s41398-020-01035-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589471PMC
October 2020

Triple isotope variations of monthly tap water in China.

Sci Data 2020 10 12;7(1):336. Epub 2020 Oct 12.

Department of Hydraulic Engineering, State Key Laboratory of Hydroscience and Engineering, Tsinghua University, Beijing, 100084, P.R. China.

Tap water isotopic compositions could potentially record information on local climate and water management practices. A new water isotope tracer O-excess became available in recent years providing additional information of the various hydrological processes. Detailed data records of tap water O-excess have not been reported. In this report, monthly tap water samples (n = 652) were collected from December 2014 to November 2015 from 92 collection sites across China. The isotopic composition (δH, δO, and δO) of tap water was analyzed by a Triple Water Vapor Isotope Analyzer (T-WVIA) based on Off-Axis Integrated Cavity Output Spectroscopy (OA-ICOS) technique and two second-order isotopic variables (d-excess and O-excess) were calculated. The geographic location information of the 92 collection sites including latitude, longitude, and elevation were also provided in this dataset. This report presents national-scale tap water isotope dataset at monthly time scale. Researchers and water resource managers who focus on the tap water issues could use them to probe the water source and water management strategies at large spatial scales.
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http://dx.doi.org/10.1038/s41597-020-00685-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550354PMC
October 2020

NLRP3 inflammasome in endothelial dysfunction.

Cell Death Dis 2020 09 18;11(9):776. Epub 2020 Sep 18.

Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.

Inflammasomes are a class of cytosolic protein complexes. They act as cytosolic innate immune signal receptors to sense pathogens and initiate inflammatory responses under physiological and pathological conditions. The NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome is the most characteristic multimeric protein complex. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18, which are mediated by caspase-1, and secretes mature forms of these mediators from cells to promote the further inflammatory process and oxidative stress. Simultaneously, cells undergo pro-inflammatory programmed cell death, termed pyroptosis. The danger signals for activating NLRP3 inflammasome are very extensive, especially reactive oxygen species (ROS), which act as an intermediate trigger to activate NLRP3 inflammasome, exacerbating subsequent inflammatory cascades and cell damage. Vascular endothelium at the site of inflammation is actively involved in the regulation of inflammation progression with important implications for cardiovascular homeostasis as a dynamically adaptable interface. Endothelial dysfunction is a hallmark and predictor for cardiovascular ailments or adverse cardiovascular events, such as coronary artery disease, diabetes mellitus, hypertension, and hypercholesterolemia. The loss of proper endothelial function may lead to tissue swelling, chronic inflammation, and the formation of thrombi. As such, elimination of endothelial cell inflammation or activation is of clinical relevance. In this review, we provided a comprehensive perspective on the pivotal role of NLRP3 inflammasome activation in aggravating oxidative stress and endothelial dysfunction and the possible underlying mechanisms. Furthermore, we highlighted the contribution of noncoding RNAs to NLRP3 inflammasome activation-associated endothelial dysfunction, and outlined potential clinical drugs targeting NLRP3 inflammasome involved in endothelial dysfunction. Collectively, this summary provides recent developments and perspectives on how NLRP3 inflammasome interferes with endothelial dysfunction and the potential research value of NLRP3 inflammasome as a potential mediator of endothelial dysfunction.
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http://dx.doi.org/10.1038/s41419-020-02985-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501262PMC
September 2020
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