Publications by authors named "Xiaohui Li"

694 Publications

Immune-Related lncRNA Signature for Predicting the Immune Landscape of Head and Neck Squamous Cell Carcinoma.

Front Mol Biosci 2021 13;8:689224. Epub 2021 Jul 13.

Department of Otorhinolaryngology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.

Long non-coding RNA (lncRNA) plays a significant role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). This article aims to develop an immune-related lncRNA (irlncRNA) model, regardless of expression levels, for risk assessment and prognosis prediction in HNSCC patients. We obtained clinical data and corresponding full transcriptome expression of HNSCC patients from TCGA, downloaded GTF files to distinguish lncRNAs from Ensembl, discerned irlncRNAs based on co-expression analysis, distinguished differentially expressed irlncRNAs (DEirlncRNAs), and paired these DEirlncRNAs. Univariate Cox regression analysis, LASSO regression analysis, and stepwise multivariate Cox regression analysis were then performed to screen lncRNA pairs, calculate the risk coefficient, and establish a prognosis model. Finally, the predictive power of this model was validated through the AUC and the ROC curves, and the AIC values of each point on the five-year ROC curve were calculated to select the maximum inflection point, which was applied as a cut-off point to divide patients into low- or high-risk groups. Based on this methodology, we were able to more effectively differentiate between these groups in terms of survival, clinico-pathological characteristics, tumor immune infiltrating status, chemotherapeutics sensitivity, and immunosuppressive molecules. A 13-irlncRNA-pair signature was built, and the ROC analysis demonstrated high sensitivity and specificity of this signature for survival prediction. The Kaplan-Meier analysis indicated that the high-risk group had a significantly shorter survival rate than the low-risk group, and the chi-squared test certified that the signature was highly related to survival status, clinical stage, T stage, and N stage. Additionally, the signature was further proven to be an independent prognostic risk factor the Cox regression analyses, and immune infiltrating analyses showed that the high-risk group had significant negative relationships with various immune infiltrations. Finally, the chemotherapeutics sensitivity and the expression level of molecular markers were also significantly different between high- and low-risk groups. The signature established by paring irlncRNAs, with regard to specific expression levels, can be utilized for survival prediction and to guide clinical therapy in HNSCC.
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http://dx.doi.org/10.3389/fmolb.2021.689224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313825PMC
July 2021

Contamination With Fumonisin B and Deoxynivalenol Is a Threat to Egg Safety and Contributes to Gizzard Ulcerations of Newborn Chickens.

Front Microbiol 2021 12;12:676671. Epub 2021 Jul 12.

College of Life Science and Engineering, Foshan University, Foshan, China.

Fumonisin B (FB) and other fumonisins, deoxynivalenol (DON), and zearalenone (ZEN) are mycotoxins (secondary metabolites of fungi) present at high levels of contamination in poultry diets and threatening the sustainability of the poultry industry and egg safety for consumers. However, residual mycotoxins in breeder eggs and their effects on chicken progeny and gizzard ulcerations remain unclear. To unveil mycotoxin contaminations from daily diets to breeder eggs, 293 poultry feed samples were collected from three large-scale poultry provinces across Northern China to Southern China. Average levels of 1,628 ± 4.36 μg/kg of FB, 593 ± 11.16 μg/kg of DON, 69 ± 9.21 μg/kg of ZEN, 52 ± 7.33 μg/kg of OTA, and 24 ± 5.85 μg/kg of AFB were found in feedstuffs and poultry diets using commercial ELISA kits. In terms of residual mycotoxins in breeder eggs, FB and DON contaminations dominated residues in egg albumen and yolk samples. Out of 221 breeder eggs, the average residual of FB in albumen were 320.6 ± 10.12 μg/kg (Hebei), 420.2 ± 10.98 μg/kg (Guangdong), and 549.4 ± 10.27 (Guangxi). Moreover, higher residual of DONs were determined in Guangdong and Guangxi provinces compared to Hebei province. ZEN, ochratoxins A (OTA), and aflatoxin B (AFB) contamination at low levels were found in the above samples collected from afronmentioned three provinces. Based on residual mycotoxins in breeder eggs, SPF embryonated eggs aged 11 days were inoculated into albumen with different doses of FB, FB or DON, or a combination of FB and DON, or a combination of FB with FB and FB. A lower hatching rate was observed in the chicken progenies with the combination of 24 μg of FB and 0.1 μg of DON compared to other treatments. Moreover, typical gizzard ulcerations with hemorrhagic lungs were observed in the progeny of breeder eggs post-inoculation of 24 μg of FB and synergetic inoculation of FB and DON. Finally, residual FB mycotoxins were detected in the gizzards and in the lungs of the progenies. Based on the above evidence, feed-borne FB and DON are dominant mycotoxins in breeder eggs and threatening food security using breeder eggs as a Trojan horse. More importantly, the residual of FB alone and in combination with of DON contamination are associated with low hatching rate and gizzard ulcerations in chicken progenies, hampering sustainable development perspectives of the poultry industry.
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http://dx.doi.org/10.3389/fmicb.2021.676671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312546PMC
July 2021

The utility of serum inhibin B, anti-Müllerian hormone and insulin growth factor-1 in predicting a positive response to GnRH analogs for diagnosing central precocious puberty in girls.

J Pediatr Endocrinol Metab 2021 Jul 21. Epub 2021 Jul 21.

Peking Union Medical College Graduate School, Beijing, P. R. China.

Objectives: The use of inhibin B (INHB), anti-Müllerian hormone (AMH) and insulin-like growth factor-1 (IGF-1) in differentiating central precocious puberty (CPP) from non-CPP was evaluated.

Methods: In total, 115 Chinese girls were recruited (CPP: 44, non-CPP: 71). The diagnostic performance of INHB, AMH and IGF-1 in differentiating CPP from non-CPP was analyzed using receiver operating characteristic (ROC) curves.

Results: INHB levels were higher in the CPP group than in the non-CPP group (55.56 ± 22.42 vs. 32.97 ± 15.59 pg/mL; p<0.001). AMH levels were similar in the CPP and non-CPP groups (6.63 ± 3.74 vs. 5.70 ± 3.15 pg/mL; p=0.158), and IGF-1 levels were much higher in the CPP group than in the non-CPP group (290.75 ± 79.78 vs. 200.10 ± 54.01 pg/mL; p<0.001). The area under the ROC curve (AUC) was greatest for INHB (0.819, standard error (SE) 0.041), followed by IGF-1 (0.809, SE 0.047) and AMH (0.567, SE 0.057). Among the ROC curves including combinations of these parameters, the AUC for INHB + IGF-1 was 0.849 and that for INHB + AMH was 0.768.

Conclusions: Serum INHB and IGF-1 measurements could predict positive responses to gonadotropin-releasing hormone (GnRH) analog stimulation in girls with precocious puberty.
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http://dx.doi.org/10.1515/jpem-2021-0137DOI Listing
July 2021

Bisindole compound 4ae ameliorated cognitive impairment in rats with vascular dementia by anti-inflammation effect via microglia cells.

Eur J Pharmacol 2021 Jul 17;908:174357. Epub 2021 Jul 17.

School of Pharmacy, Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, 475004, PR China. Electronic address:

Neuroinflammation is considered as an important mechanism of vascular dementia (VaD). Our primary study showed that the bisindole analogue (2-(2-(bis(5-chloro-1H-indol-3-yl)methyl)phenoxy)aniline, compound 4ae) had great anti-inflammation in zebrafish. Rat model of permanent occlusion of the bilateral common carotid arteries (2-vessel occlusion, 2VO) was utilized to evaluate the neuroprotective effect of 4ae. Our results showed that 4ae treatment effectively reduced Iba-1 positive microglia cells in cerebral cortex and hippocampus after cerebral ischemia. Compared with the model group, neuroinflammation characterized by Interleukin (IL)-6 and tumor necrosis factor (TNF)-α, oxidative stress characterized by reactive oxygen species (ROS) and superoxide dismutase (SOD) were both improved significantly after treatment with 4ae. Moreover, 4ae treatment significantly reversed ischemia-induced ACE enhancement, while notably increased the level of ACE2. To further elucidate the role of 4ae on neuroinflammation, we investigated the effects of 4ae on lipopolysaccharide (LPS)-induced inflammation in BV2 microglia cells, a kind of innate immune cells in central nervous system. The results demonstrated that the expressions of CD11b, TNFα and IL-6 and the level of ROS were up-regulated after treatment with LPS. More importantly, 4ae was able to block the activation of BV2 by reducing ROS production and the expression of inflammatory cytokines. In addition, our results suggested that 4ae inhibited the inflammatory response mediated by microglia cells by inhibiting NF-κB. This anti-inflammatory effect on microglia may be a potential mechanism for the neuroprotective effect of 4ae in VaD.
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http://dx.doi.org/10.1016/j.ejphar.2021.174357DOI Listing
July 2021

RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR.

J Integr Neurosci 2021 Jun;20(2):265-276

Institute of Aging and Brain Disorders, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, 230001 Hefei, Anhui, China.

Recent studies have identified multiple RNA-binding proteins tightly associated with lipid and neuronal cholesterol metabolism and cardiovascular disorders. However, the role of heterogeneous nuclear ribonucleoprotein R (hnRNPR) in cholesterol metabolism and homeostasis, whether it has a role in regulating 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), is largely unknown. This research identifies hnRNPR as a repressor of HMGCR. Knockdown and overexpression of hnRNPR in cultured neuroblastoma cell (N2a) and MN1 cell lines enhances and inhibits HMGCR , respectively. hnRNPR may exert its repressive activity on HMGCR mRNA and protein levels by using its RNA recognition motif (RRM) in recognizing and modulating the stability of HMGCR transcript. Our RNA immunoprecipitation and luciferase reporter assays demonstrate a direct interaction between hnRNPR and HMGCR mRNA. We also demonstrated that hnRNR binds to the 3' untranslated region (3' UTR) of HMGCR and reduces its translation, while hnRNPR silencing increases HMGCR expression and cholesterol levels in MN1 and N2a cells. Overexpression of HMGCR significantly restores the decreased cholesterol levels in hnRNPR administered cells. Taken together, we identify hnRNPR as a novel post-transcriptional regulator of HMGCR expression in neuronal cholesterol homeostasis.
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http://dx.doi.org/10.31083/j.jin2002026DOI Listing
June 2021

Acute hypoxia effects on Keap1/Nrf2 (Mafs)-GST pathway related oxidative metabolism in muscle of Japanese flounder (Paralichthys olivaceus).

Sci Total Environ 2021 Jul 1;795:148646. Epub 2021 Jul 1.

Key Laboratory of Mariculture, Ocean University of China, Ministry of Education, Qingdao 266003, PR China. Electronic address:

Acute hypoxia can aggravate the oxidation metabolism of fish muscle tissue. However, the molecular mechanism of oxidative metabolism in fish muscle under acute hypoxia is not very clear. We carried out effects of a typical oxidative metabolism pathway Keap1/Nrf2 (MafG)-GST on muscle oxidative metabolism of Japanese flounder (Paralichthys olivaceus) during acute hypoxia stimulation (1.65 ± 0.05 mg/L; 1 h, 3 h, 6 h, 12 h, 24 h) and reoxygenation (7.30 ± 0.08 mg/L; R12 h, R24 h, R48 h). The mRNAs of Nrf2 and GST in skeletal muscle were found co-existent, and their expressions were significant increase in 3 h and 6 h. The methylation level of CpG island1 in Nrf2 promoter, whose minimum value appeared at 3 h hypoxia treatment group, was affected by acute hypoxia, and it was negatively correlated with Nrf2 expression. The result suggests that environmental factors may regulate gene expression by epigenetic modification. Dual-luciferase reporter assay showed that GST gene was activated by transcription factor Nrf2, whose transcriptional activation binding region in GST promoter was antioxidant response element located near -980 and -852 sites, and Keap1 and MafG were Nrf2 antagonistic and synergistic factor, respectively. Furthermore, the GST activity changed with hypoxia and reoxygenation treatment in muscle, where other oxidative stress factor (MDA), antioxidant factors (T-AOC, GSH) and antioxidant enzyme activities (GST, SOD, CAT) were also changed. The results of MDA and T-AOC being further different between its hypoxia and normoxia groups (P < 0.05) at 6 h demonstrated that hypoxia stimulation lasting for 6 h would deeply affect Japanese flounder. The study illustrated that Japanese flounder responded to acute hypoxia in multiple metabolic levels by changing methylation status and transcription factor activation. It is significant to understand oxidative metabolic mechanism, analyze organism stress response and promote the scientific development of aquaculture.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148646DOI Listing
July 2021

Clinical Characteristics and Outcomes of Acute Ischemic Stroke in Patients with Type 2 Diabetes: A Single-Center, Retrospective Study in Southern China.

Int J Endocrinol 2021 14;2021:5517228. Epub 2021 Jun 14.

Department of Neurology, Huizhou Hospital Affiliated to Guangdong Medical University Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong, China.

Objective: To explore the associations between type 2 diabetes mellitus (DM) and stroke by evaluating the clinical risk factors, characteristics, and outcomes of acute ischemic stroke (AIS) patients with and without type 2 DM.

Methods: A total of 1,156 AIS patients (including 410 with type 2 DM (AIS-DM group)) and 746 without type 2 DM (AIS-NDM group)) were included. Patients' demographics, auxiliary examinations, clinical manifestations, and treatment outcomes were recorded and analyzed.

Results: Among the included AIS patients, 35.46% had type 2 DM. The AIS-DM group had less males (59.76% versus 70.64%), less smokers (33.90% versus 41.96%), more patients with hypertension (72.93% versus 63.94%; =0.002), higher triglyceride levels (42.93% versus 25.08%; ≤ 0.01), and lower total cholesterol (147.06 mg/dl versus 175.31 mg/dl) than the AIS-NDM group. The proportion of patients with large artery atherosclerosis (LAA) in the AIS-DM group was lower (77.56% versus 85.92%; < 0.05) than that in the AIS-NDM group, and the proportion of patients with small arterial occlusions (SAO) in the AIS-DM group was higher (27.07% versus 13.67%; < 0.05) than that in the AIS-NDM group. The mean National Institutes of Health Stroke Scale (NIHSS) score at admission in the AIS-DM group was lower than that in the AIS-NDM group (4.39 versus 5.00; =0.008), but there was no significant difference in the NIHSS score or the modified Rankin Scale score between the two groups at discharge. A total of 85 AIS patients underwent intravenous thrombolysis treatment with recombinant tissue plasminogen activator (rtPA). The door-to-needle time (DNT) did not differ significantly between the groups (49.39 ± 30.40 min versus 44.25 ± 15.24 min; =0.433). In addition, there were no significant differences in the baseline NIHSS score, 7-day NIHSS score, and mRS score at discharge between the groups. After intravenous thrombolysis with rtPA, the AIS-NDM group had better recovery (44.30% versus 29.20%; =0.017) and a higher ratio of good treatment outcome at discharge (65.60% versus 54.20%; =0.762).

Conclusions: Type 2 DM is associated with AIS and its risk factors, such as dyslipidemia and hypertension. Patients in the AIS-DM group had less LAA and smaller arterial occlusions, and DM could exacerbate the short-term clinical outcomes in AIS patients.
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http://dx.doi.org/10.1155/2021/5517228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216820PMC
June 2021

Computational study on the reactivity of imidazolium-functionalized manganese bipyridyl tricarbonyl electrocatalysts [Mn[bpyMe(Im-R)](CO)Br] (R = Me, Me and Me) for CO-to-CO conversion over H formation.

Phys Chem Chem Phys 2021 Jul;23(27):14940-14951

Department of Chemistry, State University of New York at Binghamton, Binghamton, New York 13902, USA.

We have recently reported a series of imidazolium-functionalized manganese bipyridyl tricarbonyl electrocatalysts, [Mn[bpyMe(Im-R)](CO)3Br]+ (R = Me, Me2, and Me4), for CO2-to-CO conversion in the presence of H2O as the proton source [J. Am. Chem. Soc., 2019, 141, 6569]. These catalysts feature slightly acidic imidazolium moieties in the secondary coordination sphere and reduce CO2 at mild electrochemical potentials. Here, we employ density functional theory (DFT) calculations to understand the electronic structure and reactivity for the CO2 reduction reaction (CO2RR) over the competing hydrogen evolution reaction (HER) using [Mn[bpyMe(ImMe)](CO)3Br]+ (1+). Our work indicates that, in the absence of water, the imidazolium ligand stabilizes the Mn-CO2 adduct through hydrogen bonding-like interactions, similar to the activated CO2 molecule in the C-cluster of the Ni,Fe-carbon monoxide dehydrogenase II, and assists the protonation steps during CO2RR and HER. More significantly, based on the energy span model, we demonstrate that the selectivity for CO2 fixation over proton reduction results from a higher activation energy for yielding the manganese dihydrogen intermediate before H2 release, which is the TOF determining transition state (TDTS) under an applied potential of Φ = -1.82 V versus Fc0/+. The calculated TOF also reflects the selectivity for CO2RR, which is four orders of magnitude larger than for HER, consistent with the CPE experiments that show no hydrogen was obtained. In the case of CO2 reduction, the TOF determining intermediate (TDI) corresponds to the doubly reduced active catalyst, 1C2(red2), which features a manganese(0) center that couples ferromagnetically with one unpaired electron in the π* orbital of bipyridine. On the other hand, for HER, the metal-hydride intermediate, 1C2(I11-R), is the TDI. Finally, second-order perturbation analyses imply that the strongest hydrogen bonding-like interaction at the C2 position in 1+ contributes to the higher catalytic activity with respect to [Mn[bpyMe(ImMe2)](CO)3Br]+ (2+) and [Mn[bpyMe(ImMe4)](CO)3Br]+ (3+) for CO2 fixation, consistent with the experimental data.
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http://dx.doi.org/10.1039/d1cp01576aDOI Listing
July 2021

Diagnosis and staging of multiple myeloma using serum-based laser-induced breakdown spectroscopy combined with machine learning methods.

Biomed Opt Express 2021 Jun 21;12(6):3584-3596. Epub 2021 May 21.

Institute of Opto-electronics, Harbin Institute of Technology, 2 Yikuang Street, 150080 Harbin, China.

Diagnosis and staging of multiple myeloma (MM) have been achieved using serum-based laser-induced breakdown spectroscopy (LIBS) in combination with machine learning methods. 130 cases of serum samples collected from registered MM patients in different progressive stages and healthy controls were deposited onto standard quantitative filter papers and ablated with a Q-switched Nd:YAG laser. Emissions of Ca, Na, K, Mg, C, H, O, N and CN were selected for malignancy diagnosis and staging. Multivariate statistics and machine learning methods, including principal component analysis (PCA), k-nearest neighbor (kNN), support vector machine (SVM) and artificial neural network (ANN) classifiers, were used to build the discrimination models. The performances of the classifiers were optimized via 10-fold cross-validation and evaluated in terms of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curves (AUC). The kNN, SVM and ANN classifiers achieved comparable discrimination performances with accuracies of over 90% for both diagnosis and staging of MM. For diagnosis of MM, the classifiers achieved performances with AUC of ∼0.970, sensitivity of ∼0.930 and specificity of ∼0.910; for staging of MM, the corresponding values were AUC of ∼0.970, sensitivity of ∼0.910 and specificity of ∼0.930. These results show that the serum-based LIBS in combination with machine learning methods can serve as a fast, less invasive, cost-effective, and robust technique for diagnosis and staging of human malignancies.
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http://dx.doi.org/10.1364/BOE.421333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221939PMC
June 2021

The effectiveness of infliximab for Kawasaki disease in children: systematic review and meta-analysis.

Transl Pediatr 2021 May;10(5):1294-1306

Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, Beijing, China.

Background: Kawasaki disease (KD) is a self-limited illness that results in coronary artery aneurysms (CAAs) and threatens children's health and lives. The therapeutic effects of single intravenous immunoglobulin gamma (IVIG) infliximab (IFX) (with or without IVIG) in young children with KD remain unclear. Thus, we made a meta-analysis and systematic review, including all of the studies which have evaluated the effectiveness and safety of IFX and IVIG KD patients.

Methods: The databases of the Cochrane Library, PubMed and Embase websites were searched for articles appearing from inception until December 31, 2020. Clinical studies that compared IFX either as initial therapy plus IVIG or rescue therapy after IVIG (IFX group) failure compared with IVIG treatment alone (IVIG group) in treating KD patients were included.

Results: The meta-analysis included nine studies characterizing 712 patients. The treatment response was significantly higher in the adjunctive IFX therapy group than in the IVIG therapy group [odds ratio (OR) 2.64; 95% CI: 1.52-4.59; P=0.0005]. Subgroup analysis, the effect of IFX therapy on treatment response is more effectiveness in the group of the high-risk KD patients than IVIG therapy (OR 6.07; 95% CI: 2.30-16.04; P=0.0003; random-effects model). Further analysis showed no difference in the improvement of CAAs in short-term follow-up between the two groups. However, adding IFX either as initial therapy or as additional therapy all showed an advantageous effect regarding the ∆Z score of the left anterior descending (LAD) (MD =0.29; 95% CI: 0.27-0.31; P<0.00001) and right coronary artery (RCA) (MD =0.24; 95% CI: 0.22-0.26; P<0.00001). Further, IFX exhibited significant effect on the treatment response compared with IVIG therapy in the Asian group (OR, 2.84; 95% CI: 1.51-5.36; P=0.001; random-effects model), and the beneficial effects of IFX were given without increasing the risk of AEs.

Conclusions: This meta-analysis emphasizes the importance of IFX on the treatment response in the high-risk KD patients. IFX may play a role in the Asian KD patients and prevention of progressive CAA, and does not increase the risk of AEs in KD patients.
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http://dx.doi.org/10.21037/tp-20-482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193009PMC
May 2021

Influence of Avoidant Coping on Posttraumatic Stress Symptoms and Job Burnout Among Firefighters: The Mediating Role of Perceived Social Support.

Disaster Med Public Health Prep 2021 Jun 28:1-6. Epub 2021 Jun 28.

School of Psychology, Nanjing Normal University, Nanjing, PRChina.

Objective: The study aims to explore the effects of avoidant coping on posttraumatic stress symptoms (PTSS) and job burnout among firefighters, and to examine the mediating role of perceived social support on the relationship between avoidant coping and PTSS and job burnout.

Method: Assessments including the posttraumatic stress disorder checklist for DSM-5 (PCL-5), Maslach Burnout Inventory-General Survey (MBI-GS), Coping Style Inventory (CSI), and Perceived Social Support Scale (PSSS) were conducted among 431 firefighters studying in a school specializing in training firemen in Nanjing, China.

Result: The results show that: (1) Avoidant coping was positively related to PTSS and job burnout among firefighters; and (2) avoidant coping was positively related to PTSS and job burnout through the mediating effect of perceived social support.

Conclusion: These findings not only provide guiding information for relevant departments to prevent mental health issues of firefighters in the future, but also enlighten the psychological intervention for firefighters, that is, to encourage firefighters to actively face and solve problems and adopt positive coping styles, as well as offer them more care and support whenever possible.
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http://dx.doi.org/10.1017/dmp.2021.155DOI Listing
June 2021

Defect density modulation of LaTiO: An effective method to suppress electron-hole recombination and improve photocatalytic nitrogen fixation.

J Colloid Interface Sci 2021 Jun 11;602:748-755. Epub 2021 Jun 11.

Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Lab for Green Catalysis and Separation, Department of Chemistry and Biology, College of Environmental and Energy Engineering, Beijing University of Technology, Beijing 100124, China.

Highly active and efficient photocatalysts are crucial for the exploration of ammonia synthesis because of the serious problem of energy deficiency. LaTiO (LTO) perovskite materials have great advantages in the field of photocatalytic nitrogen fixation because of the broadly diversified properties. The rational design of surface defect is a valid method to modulate photoinduced charge traps and create defect energy levels, especially it is an effective way to suppress the photoinduced charge recombination. Herein, LTO was obtained by a simple sol-gel method and was further reduced by NaBH to introduce oxygen defect on its surface. UV-vis spectra proved that the surface defects could reduce the band gap value of samples, which is beneficial for improving photocatalytic nitrogen fixation activity. For the best photocatalytic samples with good cycle stability, the nitrogen fixation rate is 158.13 μmol·g·h. The mechanism of photocatalytic nitrogen fixation was proposed by the PL, XPS, and PEC results, which provided possibilities for exploring more promising perovskite catalysts in the field of nitrogen fixation.
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http://dx.doi.org/10.1016/j.jcis.2021.06.055DOI Listing
June 2021

Gene Set Enrichment Analyses Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy.

Am J Ophthalmol 2021 Jun 21. Epub 2021 Jun 21.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA; Broad Institute of Harvard and MIT, Cambridge, MA.

Purpose: To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses (GSEA) applied to genome-wide association study (GWAS) meta-analyses.

Methods: We analyzed DR GWAS meta-analyses performed on 3,246 Europeans and 2,611 African Americans with type 2 diabetes. Gene sets relevant to five key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in four pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA) were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was <.05.

Results: Five gene sets were significantly enriched for multiple modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P <.05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr=.014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr=.022); lipid digestion, mobilization and transport (1.6-fold enrichment, P=.032); apoptosis (1.53-fold enrichment, P=.041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr=.049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P=.0001).

Conclusions: These GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism and cell degeneration are enriched for genes associated with DR risk.
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http://dx.doi.org/10.1016/j.ajo.2021.06.014DOI Listing
June 2021

Efficacy and Safety of Surgical Ligation versus Endovascular Embolization for Type II Congenital Extrahepatic Portosystemic Shunt.

Biomed Res Int 2021 31;2021:9951393. Epub 2021 May 31.

Institution of Oncology, Chinese PLA General Hospital, Beijing 100853, China.

Objective: To evaluate the safety and efficacy of surgical ligation and endovascular embolization for the treatment of type II congenital extrahepatic portosystemic shunt CEPS).

Methods: In this retrospective study, 23 patients diagnosed with type II CEPS between March 2011 and April 2019 were divided into either a surgical group ( = 13; 41.5 ± 19.9 years) or the interventional group ( = 10; 44.9 ± 19.7 years). The surgical group underwent laparoscopic surgical ligation of the shunt alone or ligation of the shunt and splenic artery and/or vein. The interventional group underwent endovascular embolization using microcoils, detachable coils, and vascular plug.

Results: All 23 patients received a one-step shunt closure, and their clinical symptoms were significantly improved within 3-month postprocedure and without recurrence during follow-up. The serum ammonia levels in both groups decreased after the procedure and dropped to normal level at 6- to 12-month postprocedure. Compared with baseline, the portal vein diameter in interventional group increased significantly at 3-, 6-, 12-, and 36-month postocclusion ( = 0.01 for all). The procedure time was shorter in the interventional group (127.0 ± 43.2 minutes) than the surgical group (219.8 ± 56.7 minutes; < 0.001). The intraoperative blood loss in the interventional group (32.0 ± 62.5 mL) was less than that in the surgical group (238.5 ± 396.9 mL; = 0.001).

Conclusion: Both surgical ligation and endovascular embolization are effective in the treatment of type II CEPS. Endovascular embolization has the advantages of shorter procedure time and less intraoperative blood loss. The ligation of the portosystemic shunt and splenic artery and vein is feasible with apparent safety, and it could avoid a second surgical treatment.
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http://dx.doi.org/10.1155/2021/9951393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187072PMC
May 2021

A Porcine Model of Heart Failure With Preserved Ejection Fraction Induced by Chronic Pressure Overload Characterized by Cardiac Fibrosis and Remodeling.

Front Cardiovasc Med 2021 2;8:677727. Epub 2021 Jun 2.

Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China.

Heart failure is induced by multiple pathological mechanisms, and current therapies are ineffective against heart failure with preserved ejection fraction (HFpEF). As there are limited animal models of HFpEF, its underlying mechanisms have not yet been elucidated. Here, we employed the descending aortic constriction (DAC) technique to induce chronic pressure overload in the left ventricles of Tibetan minipigs for 12 weeks. Cardiac function, pathological and cellular changes, fibrotic signaling activation, and gene expression profiles were explored. The left ventricles developed concentric hypertrophy from weeks 4 to 6 and transition to dilation starting in week 10. Notably, the left ventricular ejection fraction was maintained at >50% in the DAC group during the 12-week period. Pathological examination, biochemical analyses, and gene profile analysis revealed evidence of inflammation, fibrosis, cell death, and myofilament dephosphorylation in the myocardium of HFpEF model animals, together with gene expression shifts promoting cardiac remodeling and downregulating metabolic pathways. Furthermore, we noted the activation of several signaling proteins that impact cardiac fibrosis and remodeling, including transforming growth factor-β/SMAD family members 2/3, type I/III/V collagens, phosphatidylinositol 3-kinase, extracellular signal-regulated kinase, matrix metalloproteinases 2 and 9, tissue inhibitor of metalloproteinases 1 and 2, interleukins 6 and 1β, and inhibitor of κBα/nuclear factor-κB. Our findings demonstrate that this chronic pressure overload-induced porcine HFpEF model is a powerful tool to elucidate the mechanisms of this disease and translate preclinical findings.
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http://dx.doi.org/10.3389/fcvm.2021.677727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206269PMC
June 2021

Research on the Influence Mechanism of Epidemic Information Disclosure on Screening Authenticity Information.

Procedia Comput Sci 2021 12;187:109-115. Epub 2021 Jun 12.

Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong and 250100, China.

In early 2020, the new coronavirus pneumonia (Referred to as COVID-19) spread rapidly throughout the country, which has a major impact on economic and social development. Timely and accurate disclosure of epidemic information will enhance the public's ability to discriminate against false information. The influence mechanism of epidemic information disclosure on the identification of true and false information was studied, and the influencing factors of epidemic information disclosure were analyzed and studied under the framework of the "Technology-Organization-Environment" (TOE) model and the two-factor theory of driving factors and impeding factors. Combined with the relevant data from the Open Data Network of Shandong and Jinan and the attention of hot news events on the Internet since the outbreak of the epidemic, it is proposed that information disclosure is conducive to reasonably guiding the public attitude and enhancing the ability of information screening.
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http://dx.doi.org/10.1016/j.procs.2021.04.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197418PMC
June 2021

Multi-Path Electron Transfer in 1D Double-Shelled [email protected] C/C Tubes with Enhanced Dielectric Loss for Boosting Microwave Absorption Performance.

Small 2021 Jul 19;17(30):e2100283. Epub 2021 Jun 19.

Laboratory of Advanced Materials, Shanghai Key Lab of Molecular Catalysis and Innovative Materials, Department of Materials Science, Fudan University, Shanghai, 200438, P. R. China.

1D tubular micro-nano structural materials have been attracting extensive attention in the microwave absorption (MA) field for their anisotropy feature, outstanding impedance matching, and electromagnetic energy loss capability. Herein, unique double-shelled [email protected] C/C tubes with porous Sn inner layer and 2D Mo C/C outer layer are successfully designed and synthesized via a dual-template method. The composites possess favorable MA performance with an effective absorption bandwidth of 6.76 GHz and a maximum reflection loss value of -52.1 dB. Specifically, the rational and appropriate construction of [email protected] C/C tubes promotes the multi-path electron transfer in the composites to optimize the dielectric constant and consequently to enhance the capacity of electromagnetic wave energy dissipation. Three mechanisms dominate the MA process: i) the conductive loss resulted from the rapid electron transmission due to the novel 1D hollow coaxial multi-shelled structure, especially the metallic Sn inner layer; ii) the polarization loss caused by abundant heterogeneous interfaces of Sn-Mo C/C and Mo CC from the precise double-shelled structure; iii) the capacitor-like loss by the potential difference between Mo C/C nanosheets. This work hereby sheds light on the design of the 1D hierarchical structure and lays out a profound insight into the MA mechanism.
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http://dx.doi.org/10.1002/smll.202100283DOI Listing
July 2021

IL-10 Enhances DCs Immunity Against Infection OX40L/NLRP3 and IDO/Treg Pathways.

Front Immunol 2021 21;12:645653. Epub 2021 May 21.

Key Lab of Animal Epidemiology and Zoonoses of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China.

() is a common zoonotic agent that affects both poultry and humans. Interleukin 10 (IL-10) is an anti-inflammatory factor produced during chlamydial infection, while dendritic cells (DCs) are powerful antigen-presenting cells that induce a primary immune response in the host. However, IL-10 and DCs regulatory mechanisms in infection remain elusive. and investigations of the regulatory mechanisms were performed. IL-10 mice, conditional DCs depletion mice (zinc finger dendritic cell-diphtheria toxin receptor [zDC-DTR]), and double-deficient mice (DD, IL-10/zDC) were intranasally infected with . The results showed that more than 90% of IL-10 mice, 70% of wild-type mice, and 60% of double-deficient mice survived, whereas all zDC-DTR mice died. A higher lymphocyte proliferation index was found in the IL-10 inhibitor mice and IL-10 mice. Moreover, severe lesions and high bacterial loads were detected in the zDC-DTR mice compared with double-deficient mice. studies revealed increased OX40-OX40 ligand (OX40-OX40L) activation and CD4T cell proliferation. Besides, the expression of indoleamine 2, 3-dioxygenase (IDO), and regulatory T cells were significantly reduced in the co-culture system of CD4 T cells and IL-10 DCs in infection. Additionally, the activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome increased to facilitate the apoptosis of DCs, leading to rapid clearance of . Our study showed that IL-10 upregulated the function of deficient DCs by activating OX40-OX40L, T cells, and the NLPR3 inflammasome, and inhibiting IDO, and regulatory T cells. These effects enhanced the survival rate of mice and clearance. Our research highlights the mechanism of IL-10 interaction with DCs, OX40-OX40L, and the NLPR3 inflammasome, as potential targets against infection.
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http://dx.doi.org/10.3389/fimmu.2021.645653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176032PMC
May 2021

The association of carotid artery atherosclerosis with the estimated excretion levels of urinary sodium and potassium and their ratio in Chinese adults.

Nutr J 2021 06 6;20(1):50. Epub 2021 Jun 6.

Department of Health Management, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: Arterial stiffness is an independent cardiovascular risk factor. However, the association between sodium/potassium intake and vascular stiffness was inconsistent. Therefore, a large community-based cross-sectional study was performed to try and achieve more definitive conclusion.

Methods: Urinary sodium, potassium, and creatinine levels were tested in spot urine samples during physical examinations of each recruited participant. The 24-h estimated urinary sodium excretion (eUNaE) and estimated urinary potassium excretion (eUKE) levels were determined using the Kawasaki formula (used as a surrogate for intake). Carotid intima-media thickness (IMT) and plaques were measured using ultrasound.

Results: In 13,523 subjects aged 18-80 years, the relationships between carotid plaques and IMT with eUNaE, eUKE and their ratios were analyzed. Overall, 30.2% of participants were diagnosed with carotid artery plaques. The ratio of estimated sodium vs. potassium excretion (Na/K ratio) of the individuals with carotid artery plaques was significantly higher than that of participants without plaque (2.14 ± 0.73 vs. 2.09 ± 0.61, P < 0.01). After adjusting for age, gender, and other lifestyle covariates, a significant positive relation was found between carotid plaque and Na/K ratios (OR = 1.06, P < 0.05). In participants without plaque, a similar positive association was observed between Na/K ratios and increased bifurcation carotid IMT (β = 0.008, P < 0.01), especially in the females (P < 0.01).

Conclusions: In this study, in which sodium intake was estimated on the basis of measured urinary excretion, high estimated excretion levels of urinary sodium and/or low estimated excretion levels of urinary potassium might be associated with an increased presence of carotid atherosclerosis in Chinese individuals.
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http://dx.doi.org/10.1186/s12937-021-00710-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182948PMC
June 2021

Efficient Iterative Dynamic Kernel Principal Component Analysis Monitoring Method for the Batch Process with Super-large-scale Data Sets.

ACS Omega 2021 Apr 6;6(15):9989-9997. Epub 2021 Apr 6.

School of Electronics and Information Engineering, Liaoning University of Technology, Jinzhou 121001, China.

The Internet environment has provided massive data to the actual industrial production process. It not only has large amounts of data but also has a high data dimension, which brings challenges to the traditional statistical process monitoring. Aiming at the nonlinearity and dynamics of industrial large-scale high-dimensional data, an efficient iterative multiple dynamic kernel principal component analysis (IMDKPCA) method is proposed to monitor the complex industrial process with super-large-scale high-dimensional data. In KPCA, a new KK matrix is first created by using kernel matrix K. According to the properties of the symmetric matrix, the newly constructed matrix has the same eigenvector as the original matrix K; hence, each column of the matrix K can be used as the input sample of the iteration algorithm. After iterative operation, the kernel principal component can be deduced fleetly without the eigen decomposition. Because the kernel matrix is not stored in the algorithm beforehand, it can effectively reduce the computation complexity of the kernel. Especially for a tremendous data scale, the traditional eigen decomposition technology is no longer appropriate, yet the presented method can be solved quickly. The autoregressive moving average (ARMA) time series model and kernel principal component analysis (KPCA) are combined to build the IDKPCA model for dealing with the dynamics and nonlinearity in the industrial process. Eventually, it is applied to monitor faults in the penicillin fermentation process and compared with MKPCA to certify the accuracy and applicability of the proposed method.
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http://dx.doi.org/10.1021/acsomega.0c06039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153685PMC
April 2021

Refractory Kawasaki disease: modified methylprednisolone regimen decreases coronary artery dilatation.

Pediatr Res 2021 May 21. Epub 2021 May 21.

Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, Beijing, China.

Background: The use of corticosteroids in Kawasaki disease (KD) is still controversial. The aim of this study was to investigate the safety and effectiveness of modified methylprednisolone (mPSL) regimen as an initial treatment for refractory KD.

Methods: This is a real-world observational study. We identified refractory KD with a self-developed scoring system. Patients were divided into the intravenous immunoglobulin (IVIG) + mPSL group and the IVIG group. Clinical outcomes and changes in coronary arteries after the treatment during a 12-week period were observed. Propensity-score matching was used to analyze those patients with similar baseline characteristics.

Results: Of a total of 168 patients, 104 patients were assigned into the IVIG group and 64 patients into the IVIG + mPSL group. The therapeutic response rate of the IVIG + mPSL group was significantly higher than that of the IVIG group (98.4 vs 76.0%, P < 0.05). The IVIG + mPSL group had a shorter duration of fever and a higher rate of C-reactive protein decline than the IVIG group (1.17 ± 0.64 vs 1.81 ± 1.16 days; 88.1 vs 83.5%; P < 0.05). The luminal diameter and Z-score of the left circumflex coronary artery (LCX) were significantly smaller and lower in the IVIG + mPSL group than that in the IVIG group at weeks 2 and 12.

Conclusions: Modified mPSL regimen has minimal side effects. It might improve the initial response to IVIG and decrease the dilation of LCX for refractory KD.

Impact: Modified mPSL regimen (2-4 mg/kg/day, divided into 2-3 doses for 3-5 days, then 1 mg/kg/day, once a day for 3-5 days, then oral prednisone was tapered over 3-5 weeks in 5-7 days steps) as an intensive initial treatment can decrease LCX dilation in high-risk IVIG-resistant KD patients. Our self-developed scoring system has been proven validated and can be used to identify high-risk IVIG-resistant KD patients in North China. The present study provides an alternative therapeutic regimen for high-risk refractory KD patients.
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http://dx.doi.org/10.1038/s41390-021-01576-6DOI Listing
May 2021

Precocious Puberty in Boys: A Study Based on 5 Years of Data From a Single Center in Northern China.

J Clin Res Pediatr Endocrinol 2021 May 20. Epub 2021 May 20.

Department of Endocrinology, Children's Hospital Capital Institute of Pediatrics, Beijing, China.

Aims: To evaluate the clinical features and etiology of precocious puberty in Chinese boys.

Methods: In this study, data from boys who were referred for the evaluation of precocious puberty from 2015 to 2020 at a tertiary hospital in Northern China were retrospectively analyzed.

Results: Eighty-two boys were diagnosed with precocious puberty (PP) from 2015 to 2020. Sixty-two patients (75.6%) were diagnosed with central precocious puberty (CPP), and twenty patients (24.4%) were diagnosed with peripheral PP (PPP). In the CPP group, forty-nine cases were classified as idiopathic CPP (ICPP), and thirteen patients had pathogenic CPP. The top three causes of PPP were congenital adrenal hyperplasia (CAH), germ cell tumors (GCTs) secreting human chorionic gonadotropin (hCG) and familial male-limited precocious puberty (FMPP).

Conclusions: The etiology of precocious puberty in males is diverse. The majority of CPP cases in Chinese boys are idiopathic rather than organic.
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http://dx.doi.org/10.4274/jcrpe.galenos.2021.2021.0033DOI Listing
May 2021

Computationally efficient sandbox algorithm for multifractal analysis of large-scale complex networks with tens of millions of nodes.

Phys Rev E 2021 Apr;103(4-1):043303

Key Laboratory of Intelligent Computing and Information Processing of Ministry of Education and Hunan Key Laboratory for Computation and Simulation in Science and Engineering, Xiangtan University, Xiangtan, Hunan 411105, China.

Among various algorithms of multifractal analysis (MFA) for complex networks, the sandbox MFA algorithm behaves with the best computational efficiency. However, the existing sandbox algorithm is still computationally expensive for MFA of large-scale networks with tens of millions of nodes. It is also not clear whether MFA results can be improved by a largely increased size of a theoretical network. To tackle these challenges, a computationally efficient sandbox algorithm (CESA) is presented in this paper for MFA of large-scale networks. Distinct from the existing sandbox algorithm that uses the shortest-path distance matrix to obtain the required information for MFA of networks, our CESA employs the compressed sparse row format of the adjacency matrix and the breadth-first search technique to directly search the neighbor nodes of each layer of center nodes, and then to retrieve the required information. A theoretical analysis reveals that the CESA reduces the time complexity of the existing sandbox algorithm from cubic to quadratic, and also improves the space complexity from quadratic to linear. Then the CESA is demonstrated to be effective, efficient, and feasible through the MFA results of (u,v)-flower model networks from the fifth to the 12th generations. It enables us to study the multifractality of networks of the size of about 11 million nodes with a normal desktop computer. Furthermore, we have also found that increasing the size of (u,v)-flower model network does improve the accuracy of MFA results. Finally, our CESA is applied to a few typical real-world networks of large scale.
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http://dx.doi.org/10.1103/PhysRevE.103.043303DOI Listing
April 2021

Sex Differences in the Effect of Testosterone on Adipose Tissue Insulin Resistance From Overweight to Obese Adults.

J Clin Endocrinol Metab 2021 Jul;106(8):2252-2263

Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, China.

Objective: Adipose tissue distribution and glucose metabolism differ between men and women. Few studies have investigated sex differences in adipose tissue insulin resistance (adipose-IR). Herein, we investigated sex differences in adipose-IR in adults ranging from overweight to obese and the potential factors associated with sex differences in adipose-IR.

Methods: A total of 424 adults had their body mass index (BMI), adipose-IR, and sex hormones evaluated. Based on BMI, males and females were assigned to 4 groups.

Results: In total, males (n = 156) had higher adipose-IR than females with similar BMI levels (n = 268) (P < 0.05). Adipose-IR progressively increased from overweight to class III obesity in both males and females (all P < 0.0001); however, only in the class III obesity group was the adipose-IR significantly higher in males than in females (P = 0.025). There were significant differences in testosterone between males and females (all P < 0.01); testosterone levels were negatively correlated with adipose-IR (r = -0.333, P < 0.001) in males but positively correlated with adipose-IR (r = 0.216, P < 0.001) in females. For the logistic regression analysis, testosterone was an independent protective factor against adipose-IR in males, with an odds ratio of 0.858 (B = -0.153 [95% CI, 0.743-0.991], P = 0.037).

Conclusions: Adipose-IR reflects the progressive deterioration in adipose tissue insulin sensitivity from overweight to obesity in both males and females. Males with class III obesity have more severe adipose-IR than similarly obese females. The sex difference is associated with testosterone, and low testosterone levels may contribute to more severe adipose-IR in obese males.
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http://dx.doi.org/10.1210/clinem/dgab325DOI Listing
July 2021

Integrative analysis of miRNAs and mRNAs revealed regulation of lipid metabolism in dairy cattle.

Funct Integr Genomics 2021 Jul 7;21(3-4):393-404. Epub 2021 May 7.

College of Animal Science, Jilin University, Changchun, 130062, People's Republic of China.

Lipid metabolism in bovine mammary epithelial cells has been the primary focus of the research of milk fat percentage of dairy cattle. Functional microRNAs can affect lipid metabolism by regulating the expression of candidate genes. The purpose of the study was to screen and identify differentially expressed miRNAs, candidate genes, and co-regulatory pathways related to the metabolism of milk fat. To achieve this aim, we used miRNA and transcriptome data from the mammary epithelial cells of dairy cattle with high (H, 4.85%) and low milk fat percentages (L, 3.41%) during mid-lactation. One hundred ninety differentially expressed genes and 33 differentially expressed miRNAs were significantly enriched in related regulatory networks, of which 27 candidate genes regulated by 18 differentially expressed miRNAs significantly enriched in pathways related to lipid metabolism (p < 0.05). Target relationships between PDE4D and bta-miR-148a, PEG10 and bta-miR-877, SOD3 and bta-miR-2382-5p, and ADAMTS1 and bta-miR-2425-5p were verified using luciferase reporter assays and quantitative RT-PCR. The detection of triglyceride production in BMECs showed that bta-miR-21-3p and bta-miR-148a promote triglyceride synthesis, whereas bta-miR-124a, bta-miR-877, bta-miR-2382-5p, and bta-miR-2425-5p inhibit triglyceride synthesis. The conjoint analysis could identify functional miRNAs and regulatory candidate genes involved in lipid metabolism within the co-expression networks of the dairy cattle mammary system, which contributes to the understanding of potential regulatory mechanisms of genetic element and gene signaling networks involved in milk fat metabolism.
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http://dx.doi.org/10.1007/s10142-021-00786-9DOI Listing
July 2021

Conditional knockout of Tsc1 in RORγt-expressing cells induces brain damage and early death in mice.

J Neuroinflammation 2021 May 6;18(1):107. Epub 2021 May 6.

Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing, 400038, China.

Background: Tuberous sclerosis complex 1 (Tsc1) is known to regulate the development and function of various cell types, and RORγt is a critical transcription factor in the immune system. However, whether Tsc1 participates in regulating RORγt-expressing cells remains unknown.

Methods: We generated a mouse model in which Tsc1 was conditionally deleted from RORγt-expressing cells (Tsc1) to study the role of RORγt-expressing cells with Tsc1 deficiency in brain homeostasis.

Results: Type 3 innate lymphoid cells (ILC3s) in Tsc1 mice displayed normal development and function, and the mice showed normal Th17 cell differentiation. However, Tsc1 mice exhibited spontaneous tonic-clonic seizures and died between 4 and 6 weeks after birth. At the age of 4 weeks, mice in which Tsc1 was specifically knocked out in RORγt-expressing cells had cortical neuron defects and hippocampal structural abnormalities. Notably, over-activation of neurons and astrogliosis were observed in the cortex and hippocampus of Tsc1 mice. Moreover, expression of the γ-amino butyric acid (GABA) receptor in the brains of Tsc1 mice was decreased, and GABA supplementation prolonged the lifespan of the mice to some extent. Further experiments revealed the presence of a group of rare RORγt-expressing cells with high metabolic activity in the mouse brain.

Conclusions: Our study verifies the critical role of previously unnoticed RORγt-expressing cells in the brain and demonstrates that the Tsc1 signaling pathway in RORγt-expressing cells is important for maintaining brain homeostasis.
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http://dx.doi.org/10.1186/s12974-021-02153-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101034PMC
May 2021

A novel de novo intronic variant in ITPR1 causes Gillespie syndrome.

Am J Med Genet A 2021 Aug 5;185(8):2315-2324. Epub 2021 May 5.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

Gillespie syndrome (GLSP) is characterized by bilateral symmetric partial aplasia of the iris presenting as a fixed and large pupil, cerebellar hypoplasia with ataxia, congenital hypotonia, and varying levels of intellectual disability. GLSP is caused by either biallelic or heterozygous, dominant-negative, pathogenic variants in ITPR1. Here, we present a 5-year-old male with GLSP who was found to have a heterozygous, de novo intronic variant in ITPR1 (NM_001168272.1:c.5935-17G > A) through genome sequencing (GS). Sanger sequencing of cDNA from this individual's fibroblasts showed the retention of 15 nucleotides from intron 45, which is predicted to cause an in-frame insertion of five amino acids near the C-terminal transmembrane domain of ITPR1. In addition, qPCR and cDNA sequencing demonstrated reduced expression of both ITPR1 alleles in fibroblasts when compared to parental samples. Given the close proximity of the predicted in-frame amino acid insertion to the site of previously described heterozygous, de novo, dominant-negative, pathogenic variants in GLSP, we predict that this variant also has a dominant-negative effect on ITPR1 channel function. Overall, this is the first report of a de novo intronic variant causing GLSP, which emphasizes the utility of GS and cDNA studies for diagnosing patients with a clinical presentation of GLSP and negative clinical exome sequencing.
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http://dx.doi.org/10.1002/ajmg.a.62232DOI Listing
August 2021

Curcumin Derivative Cur20 Attenuated Cerebral Ischemic Injury by Antioxidant Effect and HIF-1α/VEGF/TFEB-Activated Angiogenesis.

Front Pharmacol 2021 15;12:648107. Epub 2021 Apr 15.

Key Laboratory of Natural Medicine and Immune Engineering, School of Pharmacy, Henan University, Kaifeng, China.

In this paper, a curcumin derivative Cur20 was synthesized for better hydrolytic stability, which showed a higher angiogenic effect on zebrafish model than curcumin. In order to reveal the potential effects on neuroprotection, a mouse model of vascular dementia (VaD) induced by permanent right common carotid artery occlusion (rUCCAO) was established. After two weeks of curcumin administration, the cognitive function of mice was detected by Morris water maze and Y maze. The alteration on oxidative injuries and morphological damage were also analyzed by reactive oxygen species, superoxide dismutase, GSH, malondialdehyde tests, and Nissl stain on cortex/hippocampus. The angiogenesis and related signal factors were evaluated as well. The results showed that Cur20 significantly attenuated the cognitive dysfunction and histopathological changes of the VaD mice with enhanced antioxidant system and angiogenesis. In addition, primary rat brain microvessel endothelial cells (rBMECs) with oxygen glucose deprivation (OGD) were applied to further verify the possible mechanisms of Cur20-induced angiogenesis. The results demonstrated that the proliferation effect and the activation of pro-angiogenesis factors such as HIF-1α, VEGF, and TFEB might contribute to the protection of ischemic injury. Based on the above, our conclusion is that Cur20 can be considered as a promising therapeutic strategy for VaD.
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http://dx.doi.org/10.3389/fphar.2021.648107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082391PMC
April 2021

Effect of root exudates on the stability and transport of graphene oxide in saturated porous media.

J Hazard Mater 2021 07 17;413:125362. Epub 2021 Feb 17.

Key Laboratory of Surficial Geochemistry of Ministry of Education, School of Earth Sciences and Engineering, Hydrosciences Department, Nanjing University, Nanjing 210023, China.

Root exudates are a major source of dissolved organic matters that strongly affect the stability and transport behaviors of nanomaterials in porous media. This study investigated the effect of citric acid (CA) and oxalic acid (OA), two common low molecular weight root exudates, on the stability and transport of graphene oxide (GO) in saturated sand columns under different combinations of pH (4.5, 7.0), ionic strength (IS: 10, 50 mM), and organic acid concentrations (10, 25 mM). Both OA and CA accelerated GO aggregation, especially under high IS and acid concentration conditions. With the presence of OA/CA (≥ 10 mM), the transport of GO was higher at pH of 7.0 than 4.5, and the GO mobility decreased with increasing IS and OA/CA concentrations, whereas, enhanced GO transport was observed at a low concentration of OA/CA (0.1 mM), indicating that the influence of organic acid was concentration-dependent. All the results suggest that perturbations of surface potential of GO and sand, as well as the chemical structure of organic acids under different solution chemistry conditions are crucial in controlling GO stability and transport behaviors. Mathematical models based on the advection-dispersion equation with one-site kinetics simulated the experimental breakthrough curves of GO very well.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125362DOI Listing
July 2021

Single-Molecule Electrochemical Transistors.

Adv Mater 2021 Apr 6:e2005883. Epub 2021 Apr 6.

State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.

Single-molecule electrochemical transistors are a type of novel molecular devices in which the tunneling current through the single-molecule junction is modulated by the electrochemical gate, and is considered a promising candidate to be employed in molecular integrated circuits for building the future "molecular computers." Benefiting from the particular interfacial electrical double layer, the current modulation process can be realized through direct orbital gating as well as electrochemical electron transfer driven by electrode potential, thus significantly enriching the functions of the transistor devices. This review focuses on the transfer characteristics and the performance of several typical types of single-molecule electrochemical transistors and the prospects for the fabrication toward integrated devices.
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http://dx.doi.org/10.1002/adma.202005883DOI Listing
April 2021
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