Publications by authors named "Xiaoying Chen"

229 Publications

Sediment characteristics and environmental quality assessment in Kompong Som Bay, Cambodia.

Mar Pollut Bull 2021 Oct 7;173(Pt A):113019. Epub 2021 Oct 7.

Department of Mineral-Geology, General Department of Mineral Resources, Ministry of Mines and Energy, Phnom Penh 12210, Cambodia.

The grain size and heavy metals (Cu, Pb, Zn, Cr, Cd, and Hg) in 42 seafloor and eight river sediments from the Kompong Som Bay of Cambodia were analyzed to identify sediment characteristics and environmental quality. The high-value areas for all the metals were mainly distributed in the northern and central parts of the bay, occupied by fine-grained sediments. There was slightly to moderately severe enrichment of Pb, Cd, and Hg in the southern and western coastal areas of Sihanoukville. Although the current ecological environment risk was relatively low, the coastal areas of Sihanoukville had low to moderate pollution of Pb, Cd, and Hg, which were closely related to pollutant emissions from the industrial production from power plants and oil refineries. It is recommended to establish a normalized monitoring mechanism and control the discharge of coastal pollutants to ensure the sustainable development of the coastal environment.
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http://dx.doi.org/10.1016/j.marpolbul.2021.113019DOI Listing
October 2021

Cardio-protective effect of tetrahydrocurcumin, the primary hydrogenated metabolite of curcumin in vivo and in vitro: Induction of apoptosis and autophagy via PI3K/AKT/mTOR pathways.

Eur J Pharmacol 2021 Sep 20;911:174495. Epub 2021 Sep 20.

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, PR China. Electronic address:

Tetrahydrocurcumin (THC) is an essential metabolite of curcumin, a major active component of the Curcuma species, which have been used traditionally for the treatment of cardiovascular diseases. The PI3K/AKT/mTOR signaling pathways serve a vital role during myocardial ischemia-reperfusion (MI/R) injury. The aim of the present study was to investigate the cardioprotective potential and mechanism of THC. In the in vivo study, an animal model of MI/R was induced by coronary occlusion. Results indicated that THC (50 mg/kg/day) protected the rat hearts from MI/R-induced heart failure by increasing ejection fraction (EF) and fractional shortening (FS) and decreasing left ventricular end systolic diameter (LVESD) and left ventricular end systolic volume (LVESV). THC also reduced myocardial infarct size and apoptosis. Furthermore, H9c2 cells were incubated with THC (20 μM) to explore its potential effect following exposure to hypoxia and reoxygenation (H/R). THC post-treatment significantly augmented cell viability and prevented lactate dehydrogenase (LDH) release after H/R exposure. THC effectively improved antioxidant activity by increasing SOD and CAT activities and decreasing MDA level. THC also enhanced mitochondrial membrane potential, inhibited apoptotic cell death, diminished the Bax/Bcl-2 ratio and cleaved caspase-3 level relative to the H/R model. In addition, THC effectively decreased Beclin1 expression and LC3 II/LC3 I ratio, but increased p62 expression, compared with the H/R model group, and decreased the formation of H/R-induced autophagosomes and autolysosomes. Furthermore, THC promoted the phosphorylation of PI3K/AKT/mTOR and induced the expression of hypoxia-inducible factor 1α (HIF-1α) after H/R. However, these effects on H9c2 cells were notably abolished by the PI3K inhibitor LY294002 and mTOR inhibitor rapamycin. In conclusion, THC effectively inhibited H/R-induced autophagy and apoptosis via, at least partially, activating the PI3K/AKT/mTOR pathways. THC might have the potential to be further developed into a potential candidate for the treatment of MI/R injury.
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http://dx.doi.org/10.1016/j.ejphar.2021.174495DOI Listing
September 2021

Complete mitochondrial genome of a tropical sea cucumber, .

Mitochondrial DNA B Resour 2021 31;6(10):2788-2790. Epub 2021 Aug 31.

Laboratory of Aquatic Sciences, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture in Rural Affairs, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China.

In this study, we report the complete mitochondrial genome of The mitogenome was 16,247 base pairs (58.55% A + T content) in length, comprising a total of 37 genes, including 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. To resolve the phylogenetic position of , we analyzed all mitochondrial protein-coding genes from 27 species within the Echinodermata. The results showed that belonged to the family and was more closely related to tropical species ( and ) than to other species. Our results will be useful for evolutionary analysis of sea cucumber species.
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http://dx.doi.org/10.1080/23802359.2021.1967218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425741PMC
August 2021

Spontaneous Ventilation Video-Assisted Thoracoscopic Surgery for Geriatric Patients With Non-Small-Cell Lung Cancer.

J Cardiothorac Vasc Anesth 2021 Jul 30. Epub 2021 Jul 30.

Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. Electronic address:

Objectives: The aim of the present study was to compare the short-term outcomes between spontaneous ventilation video-assisted thoracic surgery (SV-VATS) and mechanical ventilation video-assisted thoracic surgery (MV-VATS) in the elderly. All patients included in the present study underwent lobectomy, segmentectomy, or wedge resection and lymph node dissection.

Design: A retrospective cohor.

Setting: The first affiliated hospital of Guangzhou Medical University, Guangzhou, China.

Participants: The present study included 799 elderly patients diagnosed with non-small-cell lung cancer undergoing SV-VATS or MV-VATS. After propensity score matching, 80 patients in the SV-VATS group and 80 patients in the MV-VATS group were analyzed.

Interventions: Patients in the SV-VATS group received spontaneous-ventilation anesthesia, which was administered as follows: intravenous anesthesia + laryngeal mask airway + thoracic paravertebral block + visceral pleural surface anesthesia + thoracic vagus nerve block. Patients in the MV-VATS group received general endotracheal anesthesia. SV-VATS or MV-VATS was performed according to the preference of the patients.

Measurements And Main Results: There were no significant differences in anesthesia time (226.3 ± 79.8 v 238.5 ± 66.2 min; p = 0.44), surgery time (166.2 ± 102.6 v 170.1 ± 83.4 min; p = 0.66), and number of dissected lymph nodes (5.3 ± 7.5 v 4.4 ± 7.4; p = 0.23) between the two groups. There were significant differences in intraoperative bleeding (61.5 ± 165.1 v 82.2 ± 116.9 mL; p < 0.001). After surgery, the two groups were statistically comparable in terms of hospitalization (17.6 ± 7.6 v 17.2 ± 6.9 days; p = 0.95) and incidence of complications (7.5% v 13.8%; p = 0.20), while there were significant differences in chest tube duration (6.1 ± 3.3 v 4.5 ± 1.2 days; p < 0.001).

Conclusions: SV-VATS is feasible and as safe as MV-VATS, and it could be considered as an alternative treatment for the elderly.
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http://dx.doi.org/10.1053/j.jvca.2021.07.042DOI Listing
July 2021

Early decompressive hemicraniectomy in thrombolyzed acute ischemic stroke patients from the international ENCHANTED trial.

Sci Rep 2021 08 13;11(1):16495. Epub 2021 Aug 13.

The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

Decompressive hemicraniectomy (DHC) can improve outcomes for patients with severe forms of acute ischemic stroke (AIS), but the evidence is mainly derived from non-thrombolyzed patients. We aimed to determine the characteristics and outcomes of early DHC in thrombolyzed AIS participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analyses of ENCHANTED, an international, partial-factorial, open, blinded outcome-assessed, controlled trial in 4557 thrombolysis-eligible AIS patients randomized to low- versus standard-dose intravenous alteplase (Arm A, n = 2350), intensive versus guideline-recommended blood pressure control (Arm B, n = 1280), or both (Arms A + B, n = 947). Logistic regression models were used to identify baseline variables associated with DHC, with inverse probability of treatment weights employed to eliminate baseline imbalances between those with and without DHC. Logistic regression was also used to determine associations of DHC and clinical outcomes of death/disability, major disability, and death (defined by scores 2-6, 3-5, and 6, respectively, on the modified Rankin scale) at 90 days post-randomization. There were 95 (2.1%) thrombolyzed AIS patients who underwent DHC, who were significantly younger, of non-Asian ethnicity, and more likely to have had prior lipid-lowering treatment and severe neurological impairment from large vessel occlusion than other patients. DHC patients were more likely to receive other management interventions and have poor functional outcomes than non-DHC patients, with no relation to different doses of intravenous alteplase. Compared to other thrombolyzed AIS patients, those who received DHC had a poor prognosis from more severe disease despite intensive in-hospital management.
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http://dx.doi.org/10.1038/s41598-021-96087-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363671PMC
August 2021

Endocannabinoid activation of the TRPV1 ion channel is distinct from activation by capsaicin.

J Biol Chem 2021 Sep 30;297(3):101022. Epub 2021 Jul 30.

Department of Biophysics, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. Electronic address:

Transient receptor potential vanilloid 1 (TRPV1) ion channel serves as the detector for noxious temperature above 42 °C, pungent chemicals like capsaicin, and acidic extracellular pH. This channel has also been shown to function as an ionotropic cannabinoid receptor. Despite the solving of high-resolution three-dimensional structures of TRPV1, how endocannabinoids such as anandamide and N-arachidonoyl dopamine bind to and activate this channel remains largely unknown. Here we employed a combination of patch-clamp recording, site-directed mutagenesis, and molecular docking techniques to investigate how the endocannabinoids structurally bind to and open the TRPV1 ion channel. We found that these endocannabinoid ligands bind to the vanilloid-binding pocket of TRPV1 in the "tail-up, head-down" configuration, similar to capsaicin; however, there is a unique interaction with TRPV1 Y512 residue critical for endocannabinoid activation of TRPV1 channels. These data suggest that a differential structural mechanism is involved in TRPV1 activation by endocannabinoids compared with the classic agonist capsaicin.
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http://dx.doi.org/10.1016/j.jbc.2021.101022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387766PMC
September 2021

A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5-Mediated GDF6 Expression.

Adv Sci (Weinh) 2021 Sep 28;8(18):e2004629. Epub 2021 Jul 28.

Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, P. R. China.

Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under-explored. Human embryonic stem cell-derived mesenchymal stem cells (hES-MSCs) are shown to exert more potent cardioprotective effects against cardiac ischemia than human bone marrow-derived MSCs (hBM-MSCs), associated with enhanced neovascularization. The purpose of this study is to search for angiogenic lncRNAs enriched in hES-MSCs, and investigate their roles and mechanisms. AC103746.1 is one of the most highly expressed intergenic lncRNAs detected in hES-MSCs versus hBM-MSCs, and named as SCDAL (stem cell-derived angiogenic lncRNA). SCDAL knockdown significantly reduce the angiogenic potential and reparative effects of hES-MSCs in the infarcted hearts, while overexpression of SCDAL in either hES-MSCs or hBM-MSCs exhibits augmented angiogenesis and cardiac function recovery. Mechanistically, SCDAL induces growth differentiation factor 6 (GDF6) expression via direct interaction with SNF5 at GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis via non-canonical vascular endothelial growth factor receptor 2 activation. Furthermore, SCDAL-GDF6 is expressed in human endothelial cells, and directly enhances endothelial angiogenesis in vitro and in vivo. Thus, these findings uncover a previously unknown lncRNA-dependent regulatory circuit for angiogenesis. Targeted intervention of the SCDAL-GDF6 pathway has potential as a therapy for ischemic heart diseases.
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http://dx.doi.org/10.1002/advs.202004629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456203PMC
September 2021

Designing specific bacterial 16S primers to sequence and quantitate plant endo-bacteriome.

Sci China Life Sci 2021 Jul 22. Epub 2021 Jul 22.

State Key Laboratory of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.

Plant endophytic bacteria colonize the internal tissues of plants and interact with plants closely. The past two decades have witnessed the increasing application of next-generation 16S rRNA gene sequencing in the investigation of bacterial communities. However, deciphering plant endo-bacterial communities by this method is difficult because of the co-amplification of massive plant organellar DNAs with bacterial 16S. Here, we designed polymerase chain reaction (PCR) primer sets, including 799F/1107R, 322F/796R, and 322F-Dr/796Rs (primer pair 322F/796R with a penultimate-base substitution in 322F), that can specifically amplify bacterial 16S from plant total DNAs. We computationally and experimentally evaluated the specificity, coverage, and accuracy of the newly designed primer sets. Both 799F/1107R and 322F-Dr/796Rs produced plant DNA-free 16S amplicon libraries or reduced plant DNA contamination to lower than 5% for the plant materials with extremely-low-abundance bacterial communities. The primer set 322F-A/796R was used through absolute quantitative PCR to quantitate the population size of rice leaf or root endo-bacteriome, which revealed 10-10 and 10-10 bacteria per gram fresh weight, respectively. These 16S primer sets and amplification methods enable the simple and inexpensive next-generation sequencing and quantification of plant endo-bacteriome, which will significantly advance studies on the plant-related microbiome.
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http://dx.doi.org/10.1007/s11427-021-1953-5DOI Listing
July 2021

L₁ Sparsity-Regularized Attention Multiple-Instance Network for Hyperspectral Target Detection.

IEEE Trans Cybern 2021 Jul 8;PP. Epub 2021 Jul 8.

Attention-based deep multiple-instance learning (MIL) has been applied to many machine-learning tasks with imprecise training labels. It is also appealing in hyperspectral target detection, which only requires the label of an area containing some targets, relaxing the effort of labeling the individual pixel in the scene. This article proposes an L1 sparsity-regularized attention multiple-instance neural network (L1-attention MINN) for hyperspectral target detection with imprecise labels that enforces the discrimination of false-positive instances from positively labeled bags. The sparsity constraint applied to the attention estimated for the positive training bags strictly complies with the definition of MIL and maintains better discriminative ability. The proposed algorithm has been evaluated on both simulated and real-field hyperspectral (subpixel) target detection tasks, where advanced performance has been achieved over the state-of-the-art comparisons, showing the effectiveness of the proposed method for target detection from imprecisely labeled hyperspectral data.
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http://dx.doi.org/10.1109/TCYB.2021.3087662DOI Listing
July 2021

Mutation analysis of 28 autosomal short tandem repeats in the Chinese Han population.

Mol Biol Rep 2021 Jun 2;48(6):5363-5369. Epub 2021 Jul 2.

Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Short tandem repeats (STRs) have been extensively used in forensic genetics. However, according to previous studies, the mutation rates of STRs are relatively high and are affected by many factors. Therefore, it is important to analyze STR mutations and determine the influence of underlying factors on STR mutation rates. Mutation rates of 28 autosomal STRs were determined from 8708 paternity testing cases in the Chinese Han population, and the relationships between STR mutation rates and population, sex, age, allele length and heterozygosity were investigated. A total of 279 mutations were observed at 27 loci in a total of 233,530 meiosis cases, including 273 (97.8%) one-step, 5 (1.8%) two-step and 1 (0.4%) three-step mutations. The overall average mutation rate was 1.19 × 10 (95% CI 1.06 × 10 - 1.34 × 10) ranging from 0 (TPOX) to 2.79 × 10 (D13S325). Mutation rate comparisons revealed statistically significant differences at several STRs among populations. Paternal mutations occurred more frequently than maternal mutations, at a ratio of 6.04:1, and the mutation rate tended to increase with paternal age. Moreover, our study revealed a bias towards contraction mutations for long alleles and expansion mutations for short alleles. No obvious bias was observed in the overall mutation direction. In addition, STR loci with higher expected heterozygosity (H) tended to have higher mutation rates. This work revealed the relationships between STR mutation rates and several influencing factors, providing useful data and information for further research on STR mutations in forensic genetics.
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http://dx.doi.org/10.1007/s11033-021-06522-7DOI Listing
June 2021

Reduced Oligodendrocyte Precursor Cell Impairs Astrocytic Development in Early Life Stress.

Adv Sci (Weinh) 2021 08 21;8(16):e2101181. Epub 2021 Jun 21.

Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing, 400038, China.

Astrocyte maldevelopment is implicated in various neuropsychiatric diseases associated with early life stress. However, the underlying astrocytopathy mechanism, which can result in the psychiatric symptoms, remains unclear. In this study, it is shown that a reduced oligodendrocyte precursor cell (OPC) population accompanies hindered hippocampal astrocytic development in an improved parental isolation mouse model, and that the loss of OPCs suppresses astrocytic network formation and activity. It is further demonstrated that OPC-derived Wnt ligands, in particular Wnt7b, are required for Wnt/β-catenin pathway-mediated astrocytic development and subsequent effects related to neuronal function. In addition, focal replenishment of Wnt7a/b is sufficient to rescue astrocytic maldevelopment. These results elucidate a Wnt-paracrine-dependent but myelin-independent role of OPCs in regulating astrocytic development, which provides a unique insight into the astrocytopathy mechanism in early life stress, and can be implicated in the pathogenesis of human early life stress-related neuropsychiatric disorders.
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http://dx.doi.org/10.1002/advs.202101181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373108PMC
August 2021

Disparities between Asian and Non-Asian Thrombolyzed Acute Ischemic Stroke Patients in the Enhanced Control of Hypertension and Thrombolysis Stroke Trial.

Cerebrovasc Dis 2021 21;50(5):560-566. Epub 2021 Jun 21.

The George Institute for Global Health, Faculty of Medicine, UNSW, Sydney, New South Wales, Australia.

Background And Purpose: As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED).

Methods: ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130-140 mm Hg) or guideline-recommended (<180 mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2-6), major disability (mRS 3-5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1-24 h.

Results: Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2-6 or 3-5; adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85-1.19 [p = 0.958] and OR 0.95, 95% CI 0.80-1.13 [p = 0.572], respectively), or death (OR 1.25, 95% CI 0.95-1.65; p = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23-1.86; p = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18-2.12; p = 0.002).

Conclusions: Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups.
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http://dx.doi.org/10.1159/000516487DOI Listing
June 2021

Degradation of antibiotic Cephalosporin C in different water matrices by ionizing radiation: Degradation kinetics, pathways, and toxicity.

Sci Total Environ 2021 Oct 4;791:148253. Epub 2021 Jun 4.

Laboratory of Environmental Technology, INET, Tsinghua University, Beijing 100084, PR China; Beijing Key Laboratory of Radioactive Waste Treatment, Tsinghua University, Beijing 100084, PR China. Electronic address:

Cephalosporin antibiotics are ubiquitous emerging pollutants in various aquatic environments due to their extensive production and application. Herein, the radiolytic degradation of antibiotic Cephalosporin C (CEP-C) in different water matrices was comprehensively investigated using gamma radiation at various experimental conditions. The results revealed that CEP-C oxidation obeyed pseudo first-order kinetics, and 100%, 94.9%, 67.0%, 44.6% and 34.5% removal of CEP-C with 10-200 mg/L was achieved at 0.4 kGy, respectively. The degradation was faster at higher absorbed dose and acidic conditions (pH = 3.5). The inorganic anions, including SO, NO, and HCO, had negative influence on the degradation of CEP-C, the corresponding rate constant decreased from 4.603 to 3.667, 1.677 and 2.509 kGy respectively in the presence of SO, NO, and HCO. The analysis of intermediate products indicated that CEP-C was oxidized to generate about 10 intermediate products. Besides, it was inferred that the thioether sulfur oxidation, β-lactam ring opening, acetyl dissociation from dihydrothiazine ring and D-α-aminohexylamide group abscission were the major reaction mechanisms of CEP-C degradation by gamma radiation. Importantly, the antibacterial activity of CEP-C could be completely vanished by gamma radiation alone, while more toxic intermediate products might be formed. Addition of hydrogen peroxide and peroxymonosulfate could significantly improve the CEP-C degradation, and reduce the toxicity of intermediates of CEP-C degradation. Similar degradation behavior was observed in the groundwater and wastewater, implying that ionizing radiation can be used for degradation of Cephalosporin in water and wastewater.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148253DOI Listing
October 2021

Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target.

Int J Stroke 2021 Jun 24:17474930211025436. Epub 2021 Jun 24.

211065The George Institute for Global Health, Faculty of Medicine, 7800University of New South Wales, Sydney, Australia.

Background: We explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).

Methods: ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models.

Results: There were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56-2.90]) but comparable in MVO (1.34 [0.96-1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54-1.30]/0.48 [0.25-0.91]/0.99 [0.75-2.09], P = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74-2.38]/0.78 [0.31-1.94]/1.24 [0.64-2.41], P = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14-2.72]/0.17 [0.02-1.47]/2.69 [0.90-8.04], P = 0.05).

Conclusions: Functional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power. http://www.clinicaltrials.gov. Unique identifiers: NCT01422616.
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http://dx.doi.org/10.1177/17474930211025436DOI Listing
June 2021

miR-224-5p Carried by Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes Regulates Autophagy in Breast Cancer Cells via HOXA5.

Front Cell Dev Biol 2021 21;9:679185. Epub 2021 May 21.

Department of Clinical Laboratory Medicine, Taizhou Central Hospital (Taizhou University Hospital), Taizhou City, China.

In this study, we focused on the potential mechanism of miRNAs carried by human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-exo) in breast cancer (BC). RT-qPCR was conducted for the expression of miR-224-5p and HOXA5 in tissues and cells. After co-culture of exosomes and MCF-7 or MDA-MB-231 cells, the cell proliferation was observed by MTT and cell colony formation assay, while apoptosis was measured by flow cytometry. In addition, the expression of HOXA5 and autophagy pathway-related proteins LC3-II, Beclin-1 and P62 was detected by western blotting. And immunofluorescence was applied for detection of LC3 spots. The binding of miR-224-5p to HOXA5 was verified by the luciferase reporter gene assay and RNA-binding protein immunoprecipitation assay. Finally, experiment was performed to investigate the effect of miR-224-5p on BC growth. MiR-224-5p was up-regulated and HOXA5 was down-regulated in BC tissues and cells. HOXA5 was confirmed to be the target gene of miR-224-5p. MiR-224-5p carried by hUCMSCs-exo was able to promote the proliferation and autophagy of BC cells, while inhibited apoptosis. Bases on xenograft models in nude mice, it was also revealed that miR-224-5p carried by hUCMSCs-exo could regulate autophagy and contribute to the occurrence and development of BC . MiR-224-5p carried by hUCMSCs-exo can regulate autophagy via inhibition of HOXA5, thus affecting the proliferation and apoptosis of BC cells.
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http://dx.doi.org/10.3389/fcell.2021.679185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176026PMC
May 2021

Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.

Exp Dermatol 2021 May 28. Epub 2021 May 28.

Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves' disease (GD). Although fibroblast stimulated by thyroid-stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid-stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin-associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.
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http://dx.doi.org/10.1111/exd.14402DOI Listing
May 2021

Genetic analysis of 32 InDels in four ethnic minorities from Chinese Xinjiang.

PLoS One 2021 22;16(4):e0250206. Epub 2021 Apr 22.

Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

The present study used the previously constructed 32-plex InDels panel to investigated the genetic diversity of four ethnic minorities (Hui, Mongol, Uygur and Kazakh) from Xinjiang, and analyzed the genetic relationships between the four populations and 27 reference populations. No significant deviations were observed from the Hardy-Weinberg equilibrium (HWE) at the 32 InDels for each population. The average observed heterozygosity (Hexp), average polymorphic information content (PIC), combined power of discrimination (CPD) and cumulative probability of exclusion (CPE) for the 32 InDels were all higher than the Qiagen Investigator DIPplex kit in the four populations from Xinjiang. The CPD ranged from 0.999999999999903 (Kazakh) to 0.999999999999952 (Hui) and CPE ranged from 0.9971 (Uygur) to 0.9985 (Hui), which indicated that the 32 InDels were capable for individual identification and could be a supplementary tool in paternity test for these populations. Population genetic analysis by the method of analysis of molecular variance (AMOVA), FST, phylogenetic tree, TreeMix-based topology, multi-dimensional scale analysis (MDS), principal components analysis (PCA) and STRUCTURE analysis showed that Xinjiang Hui population has a close relationship with East Asians (EAS), especially Chinese Han, and the populations of Xinjiang Mongol, Uygur and Kazakh showed mixed ancestral components related to EAS and Europeans (EUR).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250206PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061914PMC
September 2021

A Sensitive and Rapid Assay for Mycoplasma hominis Detection Based on Recombinase Polymerase Amplification.

Clin Lab 2021 Apr;67(4)

Background: Mycoplasma hominis (MH) is an opportunistic pathogen, which often causes funisitis, spontaneous abortion, and low birth weight. However, current laboratory methods are time-consuming, labor-intensive, or require specialized laboratory instruments. Recombinase polymerase amplification (RPA) technology is a rapidly developing field because of the significance for clinical application and commercial value. Few studies have reported the use of RPA to detect MH. In this study, we developed the rapid MH detection assay, which may be potentially used as a sensitive point-of-care testing (POCT) in clinic.

Methods: Primers based on the MH 16SrRNA gene and gap gene were explored and screened out. The probe of RPA-LFD was designed based on the optimal primer and confirmed. The reaction conditions of temperature and time for RPA were optimized. The sensitivity and specificity of the analysis were explored. A total of 60 clinical specimens were used to verify the efficiency of the two methods.

Results: The optimal reaction conditions were determined as 15 minutes and 39°C. The sensitivity of RPA was 10-6 ng for MH, which is 100,000 times more sensitive than traditional PCR. Moreover, we observed another six non-target reproductive tract common pathogens without amplification products. Furthermore, we found that there was no significant difference between RPA and the cultivation method (p > 0.05). These two methods were in good agreement (κ = 0.938) when detecting clinical specimens.

Conclusions: A new method for sensitive and rapid detection of MH based on RPA was successfully developed, which can be applied in large-scale screening and as a supplementary method to classical methods.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200826DOI Listing
April 2021

Pulmonary embolism secondary to deep venous thrombosis: A retrospective and observational study for clinical characteristics and risk stratification.

Phlebology 2021 Sep 24;36(8):627-635. Epub 2021 Mar 24.

The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Objective: To investigate the risk factors, predilection sites in pulmonary embolism (PE) patients caused by deep venous thrombosis (DVT) and explore the value of scoring systems in assessing the risk of PE in DVT patients.

Methods: A total of 692 DVT patients were enrolled, and divided into no pulmonary embolism (NPE, 226, 32.66%), silent pulmonary embolism (SPE, 330, 47.67%) and featuring pulmonary embolism (FPE, 136, 19.65%) groups. For each group, the differences of clinical data and PE locations were compared, and the risk factors of PE secondary to DVT were analyzed. The predictive value of the scoring system for the diagnosis of PE and FPE was evaluated.

Results: PE presented more in the bilateral pulmonary arteries (PAs) (249, 53.43%) and has no significant difference in PESI scores in different locations. Gender, DVT locations, and previous surgery were the independent risk factors of PE. DVT locations, previous history of COPD, and previous surgical interventions were the independent risk factors of FPE. The results for areas under the ROC curves were: AUC = 0.675, AUC  = 0.601, AUC = 0.595 in the PE group; AUC = 0.722, AUC  = 0.643, AUC = 0.557 in the FPE group.

Conclusions: PE secondary to DVT mostly occurs in the bilateral PAs. Male gender, DVT locations, and previous surgery increased the risk of PE. The Wells scoring system was more advantageous for evaluating the diagnosis of PE in patients with DVT.
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http://dx.doi.org/10.1177/0268355521990964DOI Listing
September 2021

Quetiapine promotes oligodendroglial process outgrowth and membrane expansion by orchestrating the effects of Olig1.

Glia 2021 Jul 4;69(7):1709-1722. Epub 2021 Mar 4.

Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing, China.

Oligodendroglial lineage cells go through a series of morphological changes before myelination. Prior to myelination, cell processes and membrane structures enlarge by approximately 7,000 times, which is required to support axonal wrapping and myelin segment formation. Failure of these processes leads to maldevelopment and impaired myelination. Quetiapine, an atypical antipsychotic drug, was proved to promote oligodendroglial differentiation and (re)myelination, pending detailed effects and regulatory mechanism. In this study, we showed that quetiapine promotes morphological maturation of oligodendroglial lineage cells and myelin segment formation, and a short-term quetiapine treatment is sufficient to induce these changes. To uncover the underlying mechanism, we examined the effect of quetiapine on the Oligodendrocyte transcription factor 1 (Olig1). We found that quetiapine upregulates Olig1 expression level and promotes nuclear Olig1 translocation to the cytosol, where it functions not as a transcription modulator, but in a way that highly correlates with oligodendrocyte morphological transformation. In addition, quetiapine treatment reverses the negative regulatory effect of the Olig1-regulated G protein-coupled receptor 17 (GPR17) on oligodendroglial morphological maturation. Our results demonstrate that quetiapine enhances oligodendroglial differentiation and myelination by promoting cell morphological transformation. This would shed light on the orchestration of oligodendroglia developmental mechanisms, and provides new targets for further therapeutic research.
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http://dx.doi.org/10.1002/glia.23986DOI Listing
July 2021

Review of the Efficacy and Mechanisms of Traditional Chinese Medicines as a Therapeutic Option for Ionizing Radiation Induced Damage.

Front Pharmacol 2021 15;12:617559. Epub 2021 Feb 15.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Ionizing radiation damage refers to acute, delayed, or chronic tissue damage associated with ionizing radiation. Specific or effective therapeutic options for systemic injuries induced by ionizing radiation have not been developed. Studies have shown that Chinese herbal Medicine or Chinese Herbal Prescription exhibit preventive properties against radiation damage. These medicines inhibit tissue injuries and promote repair with very minimal side effects. This study reviews traditional Chinese herbal medicines and prescriptions with radiation protective effects as well as their mechanisms of action. The information obtained will guide the development of alternative radioprotectants.
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http://dx.doi.org/10.3389/fphar.2021.617559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917257PMC
February 2021

The histone deacetylase HDA703 interacts with OsBZR1 to regulate rice brassinosteroid signaling, growth and heading date through repression of Ghd7 expression.

Plant J 2020 10 14;104(2):447-459. Epub 2020 Aug 14.

State Key Laboratory of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

The plant steroid hormones brassinosteroids (BRs) play crucial roles in plant growth and development. The BR signal transduction pathway from perception to the key transcription factors has been well understood in Arabidopsis thaliana and in rice (Oryza sativa); however, the mechanisms conferring BR-mediated growth and flowering remain largely unknown, especially in rice. In this study, we show that HDA703 is a histone H4K8 and H4K12 deacetylase in rice. Hda703 mutants display a typical BR loss-of-function phenotype and reduced sensitivity to brassinolide, the most active BR. Rice plants overexpressing HDA703 exhibit some BR gain-of-function phenotypes dependent on BR biosynthesis and signaling. We also show that HDA703 is a direct target of BRASSINAZOLE-RESISTANT1 (OsBZR1), a primary regulator of rice BR signaling, and HDA703 interacts with OsBZR1 in rice. We further show that GRAIN NUMBER, PLANT HEIGHT, and HEADING DATE 7 (Ghd7), a central regulator of growth, development, and the stress response, is a direct target of OsBZR1. HDA703 directly targets Ghd7 and represses its expression through histone H4 deacetylation. HDA703-overexpressing rice plants phenocopy Ghd7-silencing rice plants in both growth and heading date. Together, our study suggests that HDA703, a histone H4 deacetylase, interacts with OsBZR1 to regulate rice BR signaling, growth, and heading date through epigenetic regulation of Ghd7.
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http://dx.doi.org/10.1111/tpj.14936DOI Listing
October 2020

Oxidative Stress-Induced Hypermethylation of KLF5 Promoter Mediated by DNMT3B Impairs Osteogenesis by Diminishing the Interaction with β-Catenin.

Antioxid Redox Signal 2021 Jul 5;35(1):1-20. Epub 2021 Apr 5.

Department of Orthopaedics, Medical College of Zhejiang University, Sir Run Run Shaw Hospital, Hangzhou, People's Republic of China.

Emerging evidence suggests that the pathogenesis of osteoporosis, characterized by impaired osteogenesis, is shifting from estrogen centric to oxidative stress. Our previous studies have shown that the zinc-finger transcription factor krüppel-like factor 5 (KLF5) plays a key role in the degeneration of nucleus pulposus and cartilage. However, its role in osteoporosis remains unknown. We aimed to investigate the effect and mechanism of KLF5 on osteogenesis under oxidative stress. First, KLF5 was required for osteogenesis and stimulated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). KLF5 was hypermethylated and downregulated in ovariectomy-induced osteoporosis mice and in BMSCs treated with HO. Interestingly, DNA methyltransferases 3B (DNMT3B) upregulation mediated the hypermethylation of KLF5 induced by oxidative stress, thereby impairing osteogenic differentiation. The inhibition of KLF5 hypermethylation using DNMT3B siRNA or 5-AZA-2-deoxycytidine (5-AZA) protected osteogenic differentiation of BMSCs from oxidative stress. Regarding the downstream mechanism, KLF5 induced β-catenin expression. More importantly, KLF5 promoted the nuclear translocation of β-catenin, which was mediated by the armadillo repeat region of β-catenin. Consistently, oxidative stress-induced KLF5 hypermethylation inhibited osteogenic differentiation by reducing the expression and nuclear translocation of β-catenin. We describe the novel effect and mechanism of KLF5 on osteogenesis under oxidative stress, which is linked to osteoporosis for the first time. Our results suggested that oxidative stress-induced hypermethylation of KLF5 mediated by DNMT3B impairs osteogenesis by diminishing the interaction with β-catenin, which is likely to contribute to osteoporosis. Targeting the hypermethylation of KLF5 might be a new strategy for the treatment of osteoporosis. 35, 1-20.
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http://dx.doi.org/10.1089/ars.2020.8200DOI Listing
July 2021

Low-Dose vs Standard-Dose Alteplase in Acute Lacunar Ischemic Stroke: The ENCHANTED Trial.

Neurology 2021 03 3;96(11):e1512-e1526. Epub 2021 Feb 3.

From The George Institute for Global Health, Faculty of Medicine (Z.Z., C.D., C.X., S. Yoshimura, C.C., T.T.-Y., A.M., X.C., M.L.H., M.W., J.C., C.S.A.), and South Western Clinical School (M.W.P.), University of New South Wales Sydney, Australia; Department of Radiology (Z.Z., J.X.), Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China; Department of Neurology (C.D., C.C., C.S.A.), Royal Prince Alfred Hospital, Sydney Health Partners; Sydney Medical School (C.D., C.C.), University of Sydney, Australia; Department of Neurosurgery (C.X.), West China Hospital, Sichuan University, Chengdu, China; Department of Cerebrovascular Medicine (S. Yoshimura, T.T.-Y.), National Cerebral and Cardiovascular Center, Osaka; Department of Neurology and Neuroscience (T.T.-Y.), Nagoya City University Graduate School of Medical Science, Japan; Department of Neurology (S. You), the Second Affiliated Hospital of Soochow University, Suzhou, China; The George Institute for Global Health, School of Public Health (M.W.), Imperial College, London; Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Center (T.G.R.), University of Leicester, UK; Melbourne Brain Centre, Royal Melbourne Hospital University Department of Medicine (M.W.P.), University of Melbourne, Australia; Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, Cumming School of Medicine (A.M.D.), University of Calgary, Canada; Westmead Applied Research Centre (R.I.L.), University of Sydney, Australia; Division of Neuroimaging Sciences, Edinburgh Imaging and Centre for Clinical Brain Sciences (G.M., J.M.W.), and UK Dementia Research Institute (J.M.W.), University of Edinburgh; and The George Institute China at Peking University Health Science Center (C.S.A.), Beijing, China.

Objective: To determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.

Methods: In a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.

Results: Of 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% confidence interval] 0.60 [0.47-0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all ≥0.07).

Conclusions: We found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.

Classification Of Evidence: This study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.

Clinical Trial Registration: Clinicaltrials.gov identifier NCT01422616.
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http://dx.doi.org/10.1212/WNL.0000000000011598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032382PMC
March 2021

Associations of an Abnormal Physiological Score With Outcomes in Acute Intracerebral Hemorrhage: INTERACT2 Study.

Stroke 2021 Jan 11;52(2):722-725. Epub 2021 Jan 11.

The George Institute China, Peking University Health Science Center, Beijing (L. Song, L. Sun, C.S.A.).

Background And Purpose: We determined associations of physiological abnormalities (systolic blood pressure, glucose, and body temperature) and warfarin use with outcomes in spontaneous intracerebral hemorrhage.

Methods: Post hoc analyses of INTERACT2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial) comparing systolic blood pressure control (<140 versus <180 mm Hg) in 2839 hypertensive patients with intracerebral hemorrhage (onset <6 hours). Multivariable logistic regression defined associations of baseline scores assigned as 0 to 6 per 10 mm Hg systolic blood pressure increase (range, 150-220 mm Hg) and 0 or 1 for serum glucose (≤6.5 versus >6.5 mmol/L), body temperature (≤37.5 °C versus >37.5 °C), and warfarin use (no versus yes) and death or major disability (modified Rankin Scale scores 3-6 at 90 days).

Results: Baseline score distribution was 0 (7.7%), 1 (15.6%), 2 (19.0%), 3 (19.1%), 4 (15.2%), 5 (11.6%), 6 (8.9%), and 7 (2.9%). After adjustment for baseline neurological severity and potential confounders, significant linear associations were evident for increasing (per point) score and death or major disability (odds ratio, 1.12 [95% CI, 1.07-1.17]), death (odds ratio, 1.15 [95% CI, 1.07-1.23]), and major disability (odds ratio, 1.10 [95% CI, 1.05-1.15]).

Conclusions: Combination of abnormal physiological parameters and warfarin use is associated with poor outcomes in intracerebral hemorrhage. Effects of their early control is under investigation in INTERACT3 (Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00716079.
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http://dx.doi.org/10.1161/STROKEAHA.120.030435DOI Listing
January 2021

The association between herpes simplex virus type 1 infection and Alzheimer's disease.

J Clin Neurosci 2020 Dec 8;82(Pt A):63-70. Epub 2020 Nov 8.

Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address:

There is growing evidence demonstrating the relationship between herpes simplex virus type 1 (HSV-1) infection and Alzheimer's disease (AD). We searched PubMed, Embase, and Cochrane databases for relevant articles. The Newcastle-Ottawa Scale (NOS) was used to evaluate the qualities of these studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. We also performed subgroup analyses stratified by apolipoprotein ε4 (APOE ε4), NOS score, and the method of confirming AD. A total of 21 studies between 1990 and 2020 were identified. The pooled OR suggested that HSV-1 infection is a risk factor of AD: pooled OR 1.40 (95% CI: 1.13-1.75; I = 3%, P = 0.42). In the subgroup analyses, the pooled ORs of HSV-1 infection associated with AD were 0.75 (95% CI: 0.24-2.37) among the APOE ε4-positive individuals; 0.85 (95% CI: 0.61-1.17) among the APOE ε4-negative individuals; 1.51 (95% CI: 1.10-2.06) in the high NOS score studies; 1.23 (95% CI: 0.85-1.76) in the moderate NOS score studies; 1.47 (95% CI: 1.16-1.87) in the clinical diagnosis group, and 1.20 (95% CI: 0.77-1.87) in the autopsy group. Our up-to-date systematic review and meta-analysis suggest that HSV-1 infection is a risk factor of AD.
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http://dx.doi.org/10.1016/j.jocn.2020.10.044DOI Listing
December 2020

Small Molecule Phenotypic Screen Identifies Novel Regulators of LDLR Expression.

ACS Chem Biol 2020 12 3;15(12):3262-3274. Epub 2020 Dec 3.

AbbVie Inc., 1 North Waukegan Road, North Chicago, Illinois 60064, United States.

Alzheimer's Disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The current treatment options for AD are limited to ameliorating cognitive decline temporarily and not reversing or preventing the progression of dementia. Hence, more effective therapeutic strategies are needed to combat this devastating disease. The low-density lipoprotein receptor has been shown to modulate the neuronal metabolism of cholesterol and apolipoprotein E, a major genetic risk factor for AD. LDLR overexpression in mice has been shown to increase amyloid-β clearance and reduce amyloid deposition. We conducted a phenotypic screen to identify novel signaling pathways and targets that regulate LDLR expression in glial cells using an annotated compound library of approximately 29 000 compounds. The screen identified novel targets such as polo like kinase 1 (PLK1), activin receptor like kinase 5 (ALK5), and serotonin transporter (SERT). We used genetic, chemical biology and pathway analysis to confirm the target hypothesis. This work highlights that phenotypic screening is a promising strategy to identify novel mechanisms and targets for therapeutic intervention of complex neurodegenerative disorders.
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http://dx.doi.org/10.1021/acschembio.0c00851DOI Listing
December 2020

Astrocyte deletion of α2-Na/K ATPase triggers episodic motor paralysis in mice via a metabolic pathway.

Nat Commun 2020 12 2;11(1):6164. Epub 2020 Dec 2.

Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Familial hemiplegic migraine is an episodic neurological disorder characterized by transient sensory and motor symptoms and signs. Mutations of the ion pump α2-Na/K ATPase cause familial hemiplegic migraine, but the mechanisms by which α2-Na/K ATPase mutations lead to the migraine phenotype remain incompletely understood. Here, we show that mice in which α2-Na/K ATPase is conditionally deleted in astrocytes display episodic paralysis. Functional neuroimaging reveals that conditional α2-Na/K ATPase knockout triggers spontaneous cortical spreading depression events that are associated with EEG low voltage activity events, which correlate with transient motor impairment in these mice. Transcriptomic and metabolomic analyses show that α2-Na/K ATPase loss alters metabolic gene expression with consequent serine and glycine elevation in the brain. A serine- and glycine-free diet rescues the transient motor impairment in conditional α2-Na/K ATPase knockout mice. Together, our findings define a metabolic mechanism regulated by astrocytic α2-Na/K ATPase that triggers episodic motor paralysis in mice.
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http://dx.doi.org/10.1038/s41467-020-19915-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710756PMC
December 2020

Conversion between Mini-Mental State Examination and Montreal Cognitive Assessment scores in older adults undergoing selective surgery using Rasch analysis.

J Adv Nurs 2021 Feb 29;77(2):729-741. Epub 2020 Nov 29.

Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Aims: To develop and validate a conversion table between the MMSE and the MoCA using Rasch analysis in older adults undergoing selective surgery and examine its diagnostic accuracy in detecting cognitive impairment.

Design: Cross-sectional study.

Methods: Older patients [N = 129; age 66.0 (4.6) years, education 7.7 (3.5) years] undergoing elective surgery were recruited from December 2017 to June 2018. All participants completed the MMSE and MoCA and 113 of them completed a battery of neuropsychological tests. Common person linking based on Rasch analysis was performed to develop the conversion table. The conversions were validated by calculating the intraclass correlation coefficient (ICC), score differences between actual and converted scores, and root mean squared error of the difference (RMSE). The diagnostic accuracy of the conversions for detecting cognitive impairment was also tested.

Results: The MoCA [person measure: 1.3 (1.1) logits] was better targeted to the patients than the MMSE [person measure: 3.2 (1.3) logits]. Conversion from MoCA to MMSE scores (ICC 0.84, 95% CI 0.77-0.88; RMSE 1.36) was more precise than conversion from MMSE to MoCA (ICC 0.82, 95% CI 0.75-0.87; RMSE 2.56). Conversion from MoCA to MMSE demonstrated better diagnostic accuracy in detecting cognitive impairment than the actual MMSE, whereas conversion from MMSE to MoCA exhibited the opposite pattern.

Conclusion: Conversion from MoCA to MMSE was more precise and had better diagnostic accuracy in detecting pre-operative cognitive impairment in older patients undergoing selective surgery than conversion from MMSE into MoCA.

Impact: The finding is useful for interpreting, comparing, and integrating cognitive measurements in surgical settings and clinical research. Statistically sound conversion between MoCA and MMSE based on Rasch analysis is now possible for surgical setting and clinical research.
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http://dx.doi.org/10.1111/jan.14638DOI Listing
February 2021

Working memory training improves emotion regulation in drug abstainers: Evidence from frontal alpha asymmetry.

Neurosci Lett 2021 01 20;742:135513. Epub 2020 Nov 20.

Department of Psychology, School of Social and Behavior Sciences, Nanjing University, Nanjing, 210023, China. Electronic address:

Drug addiction has been associated with unsuccessful emotion regulation, which can be improved by working memory training (WMT) in healthy populations. This study aimed to assess the effect of WMT on emotion regulation in drug abstainers. We divided 40 male drug abstainers into two groups: (i) the training group (n=20) participated in a running memory task for 20 days, and (ii) the control group (n=20) did not participate in any training task. We assessed the emotion regulation questionnaire (ERQ) and frontal electroencephalographic (EEG) activity while viewing pictures (including neutral, positive, negative and drug-related contents) for all participants before and after the training. After WMT for 20 days, the training group adopted more spontaneous emotion regulation strategies compared with control group. The asymmetry scores of training group improved while viewing negative and drug-related pictures compared to pretest, which suggests that they converted from right-brain asymmetry to left-brain asymmetry. However, the control group declined both in the ERQ scores and the asymmetry scores. These results suggest that WMT improves the emotion regulation of drug abstainers.
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http://dx.doi.org/10.1016/j.neulet.2020.135513DOI Listing
January 2021
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