Publications by authors named "Xiaojing Wang"

627 Publications

Enforcement agencies and smoke-free policy compliance: An observational study in Qingdao, China.

Tob Induc Dis 2021 12;19:26. Epub 2021 Apr 12.

Institute for Global Tobacco Control, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States.

Introduction: In recent years, tobacco control policy initiatives have emerged at the subnational level in China. In 2013, for example, Qingdao enacted a 100% smoke-free policy that gave regulatory authority to multiple enforcement agencies. Given that little is known about the extent of smoke-free policy compliance in smaller Chinese cities, this study assessed compliance with Qingdao's Tobacco Control Regulation and whether compliance differed by enforcement agency.

Methods: A cross-sectional observational study was undertaken between October and November 2018. Venues were selected based on enforcement agency and included restaurants, retail stores, schools, government buildings, hospitals, business offices, and other hospitality venues. Comprehensive lists of venues were identified where they existed, and a random sample of venues were subsequently selected. For venue categories for which there were no comprehensive lists, a walking protocol was used. Observational data included evidence of smoking, the presence of no-smoking signage, and designated smoking areas (DSAs). Descriptive statistics were obtained. Subsequently, logistic regression models were used to determine the association between enforcement agency and policy compliance.

Results: A total of 694 venues were observed. For all venue types, 64.7% were compliant with the composite indicator 'evidence of smoking'. Findings also showed that smoke-free compliance varied by enforcement agency (p<0.001). Venues with evidence of smoking and not posting of no-smoking signs at the main entrance were lowest among venues that fall under Public Security Bureau. Compliance with posting no-smoking signs inside was lowest in venues that fall under the Industry and Commercial Administration (I&C). While Qingdao's smoke-free policy prohibits DSAs, our findings showed that 2% of venues that fall under the jurisdiction of I&C had DSAs.

Conclusions: An effective coordination mechanism that can ensure a consistent and standardized approach is urgently needed in Qingdao. With such a concerted effort, it will be possible to achieve the target of 100% smoke-free indoor places in Qingdao.
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http://dx.doi.org/10.18332/tid/133635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040544PMC
April 2021

Thalamocortical Functional Connectivity in Patients With White Matter Hyperintensities.

Front Aging Neurosci 2021 18;13:632237. Epub 2021 Mar 18.

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

White matter hyperintensities (WMH)s is a very common neuroradiological manifestation in the elderly and is an increased risk of dementia and cognitive decline. As we all know, the thalamocortical circuit plays an important part in cognition regulation. However, the role of this circuit in WMHs and its related cognitive deficits is still unclear. Eighty WMH patients and 37 healthy controls (HCs) were enrolled in the current study. WMH patients were divided into a mild WMH group ( = 33) and moderate-severe WMH group ( = 47) according to Fazekas scores. Resting-state functional magnetic resonance imaging (rs-fMRI) data of all participants were collected for thalamocortical functional connectivity (FC) analysis. The analysis was performed in two steps. First, the whole cerebral cortex was divided into six regions of interest (ROIs), which were used as seeds to investigate the changes of FC with the thalamus. Then, the subregion of the thalamus generated in the previous step was used as the seed for FC analysis with the whole brain. In the first step of FC analysis, it was found that precentral gyrus (PrCG)-interthalamic adhesion (ITA) FC values in moderate-severe WMH group were higher than those in HC and mild WMH groups. However, when compared with the HC group, the increase of PrCG-ITA FC values in mild WMH group was not statistically significant. In the second step of FC analysis, the ITA was set as the seed, and compared with the HC group, the results showed that the FC values of the ITA-medial frontal gyrus (MFG) in mild group and moderate-severe WMH groups were significantly increased. In addition, the FC values in moderate-severe group were significantly higher than those in mild group. Finally, it was also found that FC values (PrCG-ITA and ITA-MFG) were significantly correlated with neuropsychological test results for multiple cognitive functions such as memory, execution and attention in WMH patients. Abnormal thalamocortical FC was closely related with cognitive impairments in WMH patients.
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http://dx.doi.org/10.3389/fnagi.2021.632237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012554PMC
March 2021

Mechanism of the Alcohol-Soluble Ionic Organic Interlayer in Organic Solar Cells.

Langmuir 2021 Apr 2;37(14):4347-4354. Epub 2021 Apr 2.

State Key Laboratory of Luminescent Materials and Devices, Institute of Polymer Optoelectronic Materials and Devices, South China University of Technology, Guangzhou 510640, P. R. China.

In this article combining density functional theory (DFT) calculations and corresponding experimental measurements, the adsorption behaviors and working mechanism of the alcohol-soluble ionic organic interlayer on different electrode substrates were studied. The results suggest that, when the ionic organic bipyridine salt interlayer (FPyBr) is adsorbed on the Ag surface, Br will break away from molecule chains and form new chemical bonds with the Ag substrate, as confirmed by both the X-ray photoelectron spectroscopy (XPS) study and DFT study for the first time. Charges are further found to transfer to the Ag substrate from the new interlayer molecular structure without Br, resulting in adsorption dipoles directed from Ag to the interlayer. Moreover, the direction of the intrinsic dipole of the molecule itself on the Ag substrate is also verified, which is the same as that of the adsorption dipole. Subsequently, the superposition of the two dipoles results in a large reduction of the Ag substrate work function. In addition, the dipole formation mechanism of the interlayer on the ITO surface was also studied. The change in the work function of the ITO substrate by this interlayer is found to be smaller than that of Ag as confirmed by both a DFT study and scanning Kelvin probe microscopy (SKPM) results, which is mainly due to the reversed direction of the molecular intrinsic dipole with respect to the interfacial dipole. The worst device performance of organic solar cells based on the ITO-FPyBr substrate is considered to be one of the consequences of the feature. The findings here are of great importance for the study of the mechanism of the ionic organic interlayer in organic electronic devices, providing insightful understandings on how to further improve the material and device performance.
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http://dx.doi.org/10.1021/acs.langmuir.1c00413DOI Listing
April 2021

TNF-induced necroptosis initiates early autophagy events via RIPK3-dependent AMPK activation, but inhibits late autophagy.

Autophagy 2021 Mar 28:1-18. Epub 2021 Mar 28.

Institute of Molecular Medicine I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Macroautophagy/autophagy and necroptosis represent two opposing cellular s tress responses. Whereas autophagy primarily fulfills a cyto-protective function, necroptosis is a form of regulated cell death induced via death receptors. Here, we aimed at investigating the molecular crosstalk between these two pathways. We observed that RIPK3 directly associates with AMPK and phosphorylates its catalytic subunit PRKAA1/2 at T183/T172. Activated AMPK then phosphorylates the autophagy-regulating proteins ULK1 and BECN1. However, the lysosomal degradation of autophagosomes is blocked by TNF-induced necroptosis. Specifically, we observed dysregulated SNARE complexes upon TNF treatment; e.g., reduced levels of full-length STX17. In summary, we identified RIPK3 as an AMPK-activating kinase and thus a direct link between autophagy- and necroptosis-regulating kinases. ACACA/ACC: acetyl-CoA carboxylase alpha; AMPK: AMP-activated protein kinase; ATG: autophagy-related; BECN1: beclin 1; GFP: green fluorescent protein; EBSS: Earle's balanced salt solution; Hs: ; KO: knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; MLKL: mixed lineage kinase domain like pseudokinase; Mm: ; MTOR: mechanistic target of rapamycin kinase; MVB: multivesicular body; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4/VPS15: phosphoinositide-3-kinase regulatory subunit 4; PLA: proximity ligation assay; PRKAA1: protein kinase AMP-activated catalytic subunit alpha 1; PRKAA2: protein kinase AMP-activated catalytic subunit alpha 2; PRKAB2: protein kinase AMP-activated non-catalytic subunit beta 2; PRKAG1: protein kinase AMP-activated non-catalytic subunit gamma 1; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; RIPK1: receptor interacting serine/threonine kinase 1; RIPK3: receptor interacting serine/threonine kinase 3; SNAP29: synaptosome associated protein 29; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; STX7: syntaxin 7; STX17: syntaxin 17; TAX1BP1: Tax1 binding protein 1; TNF: tumor necrosis factor; ULK1: unc-51 like autophagy activating kinase 1; VAMP8: vesicle associated membrane protein 8; WT: wild-type.
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http://dx.doi.org/10.1080/15548627.2021.1899667DOI Listing
March 2021

Immunological Characteristics in Type 2 Diabetes Mellitus Among COVID-19 Patients.

Front Endocrinol (Lausanne) 2021 11;12:596518. Epub 2021 Mar 11.

Department of Pediatrics, Center for the Diagnosis of Genetic Metabolic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04365634.

Context: Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear.

Objective: We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients.

Design And Methods: In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups.

Results: Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4 T cells, CD8 T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8 T cells and NK cells than survivors.

Conclusion: The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8 T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.
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http://dx.doi.org/10.3389/fendo.2021.596518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992040PMC
April 2021

Novel Copper(II) Complex with a 4-Acylpyrazolone Derivative and Coligand Induce Apoptosis in Liver Cancer Cells.

ACS Med Chem Lett 2021 Mar 26;12(3):467-476. Epub 2021 Feb 26.

College of Life Sciences, Xinjiang Normal University, Urumqi 830054, China.

A novel pyrazolone-based copper complex [CuL(phen)(CHOH)][CuL(phen)]·CHCHOH·CHOH (P-FAH-Cu-phen) was synthesized and characterized. The asymmetric structural unit of P-FAH-Cu-phen was composed of two independent complex units [CuL(phen)(CHOH)] and [CuL(phen)]:Cu1 center with six coordination mode and Cu2 center with five coordination mode. The growth of BEL-7404 cells and H22 cells was significantly inhibited by P-FAH-Cu-phen with IC values of 1.175 μg/mL and 1.097 μg/mL, respectively, which were much lower than IC of cisplatin for BEL-7404 cells (23.32 μg/mL) and H22 cells (27.5 μg/mL). P-FAH-Cu-phen induced cell cycle arrest at G2/M and apoptosis in BEL-7404 cells through mitochondria- and endoplasmic reticulum stress-associated pathways. Moreover, P-FAH-Cu-phen significantly suppressed the migration of BEL-7404 cells and the tumor growth in H22 tumor mouse model without severe side effects and improved the survival of tumor mice. The results suggested that P-FAH-Cu-phen might be a potential drug candidate for the treatment of live cancer.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957940PMC
March 2021

Yindan Jiedu Granules, a Traditional Chinese Medicinal Formulation, as a Potential Treatment for Coronavirus Disease 2019.

Front Pharmacol 2020 5;11:634266. Epub 2021 Feb 5.

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Granules (YDJDG) have been newly prescribed as a Chinese herbal formula. This study aimed to compare the efficacy of YDJDG and lopinavir-ritonavir in the treatment of coronavirus disease 2019 (COVID-19). Overall, 131 patients with COVID-19 were included in this study. In addition to standard care, 60 of these patients received YDJDG (YDJDG group) and 71 received lopinavir-ritonavir (lopinavir-ritonavir group). Propensity score matching (PSM) was used to match the characteristics of individuals in the two groups, while the Kaplan-Meier method was used to compare the proportion recovery observed. Cox analysis revealed that YDJDG and CD4 ≥ 660 cells/µL were independent predictive factors of proportion recovery. At baseline, disease types differed between the YDJDG and lopinavir-ritonavir treatment groups. Furthermore, no significant adverse effects or toxicities relevant to YDJDG were observed. The median recovery time was 21 days in the YDJDG group and 27 days in the lopinavir-ritonavir group. After PSM (1:1), 50 patient pairs, YDJDG vs. lopinavir-ritonavir, were analyzed. In the YDJDG group, the proportion of recovered patients was remarkably higher than that observed in the lopinavir-ritonavir group ( = 0.0013), especially for those presenting mild/moderate disease type and CD4 < 660 cells/µL. In the YDJDG group, the mean duration of fever and pulmonary exudative lesions was significantly shorter than that observed in the lopinavir-ritonavir group ( = 0.0180 and = 0.0028, respectively). YDJDG reveals the potential to hasten the recovery period in COVID-19 patients with mild/moderate disease type or CD4 < 660 cells/µL by shortening the mean duration of fever and pulmonary exudative lesions.
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http://dx.doi.org/10.3389/fphar.2020.634266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957926PMC
February 2021

Case Report: Proven Diagnosis of Culture-Negative Chronic Disseminated Candidiasis in a Patient Suffering From Hematological Malignancy: Combined Application of mNGS and CFW Staining.

Front Med (Lausanne) 2021 24;8:627166. Epub 2021 Feb 24.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Chronic disseminated candidiasis (CDC) is a severe complication with high morbidity and mortality in patients with hematological malignancies who have undergone chemotherapy. Blood or sterile liver biopsy cultures are negative due to recurrent empirical antifungal therapy. With the escalating resistance to azole-based antifungal drugs in infection by species, pathogen identification is becoming increasingly important for determining definitive diagnosis and treatment strategy. In this case report, we present, for the first time, diagnostic confirmation of a culture-negative CDC case with infection using a combination of metagenomics next-generation sequencing and calcofluor white staining.
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http://dx.doi.org/10.3389/fmed.2021.627166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943471PMC
February 2021

A new HLA-DQB1 allele, HLA-DQB1*04:62, identified in a Chinese family.

HLA 2021 Mar 13. Epub 2021 Mar 13.

Department of Pathology and Lab Medicine, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

HLA-DQB1*04:62 differs from HLA-DQB1*04:01:01:01 by a single nucleotide in exon 3 (433A->G, N113D).
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http://dx.doi.org/10.1111/tan.14257DOI Listing
March 2021

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial.

Front Med 2021 Mar 9. Epub 2021 Mar 9.

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, 230001, China.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
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http://dx.doi.org/10.1007/s11684-020-0824-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940448PMC
March 2021

Fine-tuning pharmacological properties of mirtazapine antidepressant drug: a theoretical study.

J Biomol Struct Dyn 2021 Mar 9:1-9. Epub 2021 Mar 9.

Department of Chemistry, Arizona State University, Tempe, AZ, USA.

It has become obvious that fluorinated drugs have a significant role in medicinal applications. In this study, the fluorination of mirtazapine antidepressant drug was investigated using density functional theory calculations. We found that the intramolecular hydrogen bonding and charge transfers of the mirtazapine drug were influenced by fluorine substitution. Our results also reveal that the fluorination altered the stability, solubility, and molecular polarity of the mirtazapine antidepressant drug. Moreover, our results show that the electronic spectra of fluorinated derivatives of the mirtazapine exhibit a red shift toward higher wavelengths compared to the original antidepressant drug. Our calculations show that the difference between value of the gas and water (Δ) of fluorinated derivatives of the mirtazapine drug was negative. We also found that the fluorination can increases the first hyperpolarizability of the mirtazapine antidepressant drug. Our results present an efficient strategy to improve the nonlinear optical responses of the antidepressant drugs. Consequently, the results of present study show that the fluorination of mirtazapine could be considered as a promising strategy to design antidepressant drugs with better pharmacological properties.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1896386DOI Listing
March 2021

Qishen Yiqi Dripping Pill Protects Against Diabetic Nephropathy by Inhibiting the Wnt/β-Catenin and Transforming Growth Factor-β/Smad Signaling Pathways in Rats.

Front Physiol 2020 19;11:613324. Epub 2021 Feb 19.

Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Diabetic nephropathy is a severe microvascular complication of diabetes. Qishen Yiqi dripping pill (QYDP) has been reported to be a renal protective drug. However, the mechanisms remain unclear. This study was performed to investigate the mechanisms. In this study, Sprague-Dawley rats were injected with streptozotocin to generate a diabetes model. Diabetic rats were administered 150 or 300 mg/kg/day QYDP. After 8 weeks of treatment, serum creatinine, serum blood urea nitrogen, and 24-h urinary albumin were measured. Kidney histological staining and immunostaining were analyzed. Then, the renal tissue was analyzed with a genome expression array. The results showed that QYDP treatment reduced serum creatinine, blood urea nitrogen, and 24-h urinary albumin and improved kidney histology and fibrosis. The gene array revealed that the expression of 189 genes was increased, and that of 127 genes was decreased in the high dosage QYDP group compared with the diabetic group. Pathway and gene ontology analyses showed that the differentially expressed genes were involved in the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad2 signaling pathways. QYDP reduced the renal Wnt1, catenin β1, Tgfb1, and Smad2 gene expression and β-catenin, TGF-β, Smad2, collagen I, α-smooth muscle actin, and fibronectin protein expression in diabetic rats. Our results provide the first evidence that QYDP performs its renal-protective function by inhibiting the Wnt/β-catenin and TGF-β/Smad2 signaling pathways in diabetic rats.
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http://dx.doi.org/10.3389/fphys.2020.613324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933526PMC
February 2021

Trained immunity contributes to the prevention of infection, a novel role of autophagy.

Emerg Microbes Infect 2021 Dec;10(1):578-588

Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, and Department of Laboratory Medicine, Bengbu Medical College, Bengbu, People's Republic of China.

Mycobacterium tuberculosis () is the pathogen which causes tuberculosis (TB), a significant human public health threat. Co-infection of and the human immunodeficiency virus (HIV), emergence of drug resistant , and failure to develop highly effective TB vaccines have limited control of the TB epidemic. Trained immunity is an enhanced innate immune response which functions independently of the adaptive/acquired immune system and responds non-specifically to reinfection with invading agents. Recently, several studies have found trained immunity has the capability to control and eliminate infection. Over the past decades, however, the consensus was adaptive immunity is the only protective mechanism by which hosts inhibit growth. Furthermore, autophagy plays an essential role in the development of trained immunity. Further investigation of trained immunity, infection, and the role of autophagy in this process provide new possibilities for vaccine development. In this review, we present the general characteristics of trained immunity and autophagy. We additionally summarize several examples where initiation of trained immunity contributes to the prevention of infection and propose future directions for research in this area.
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http://dx.doi.org/10.1080/22221751.2021.1899771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018485PMC
December 2021

Neurog2 directly converts astrocytes into functional neurons in midbrain and spinal cord.

Cell Death Dis 2021 Mar 1;12(3):225. Epub 2021 Mar 1.

Department of Neurology, Jiading District Central Hospital Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, 201800, China.

Conversion of astrocytes into neurons in vivo offers an alternative therapeutic approach for neuronal loss after injury or disease. However, not only the efficiency of the conversion of astrocytes into functional neurons by single Neurog2, but also the conundrum that whether Neurog2-induced neuronal cells (Neurog2-iNs) are further functionally integrated into existing matured neural circuits remains unknown. Here, we adopted the AAV(2/8) delivery system to overexpress single factor Neurog2 into astrocytes and found that the majority of astrocytes were successfully converted into neuronal cells in multiple brain regions, including the midbrain and spinal cord. In the midbrain, Neurog2-induced neuronal cells (Neurog2-iNs) exhibit neuronal morphology, mature electrophysiological properties, glutamatergic identity (about 60%), and synapse-like configuration local circuits. In the spinal cord, astrocytes from both the intact and lesioned sources could be converted into functional neurons with ectopic expression of Neurog2 alone. Notably, further evidence from our study also proves that Neurog2-iNs in the intact spinal cord are capable of responding to diverse afferent inputs from dorsal root ganglion (DRG). Together, this study does not merely demonstrate the feasibility of Neurog2 for efficient in vivo reprogramming, it gives an indication for the Neurog2-iNs as a functional and potential factor in cell-replacement therapy.
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http://dx.doi.org/10.1038/s41419-021-03498-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921562PMC
March 2021

Targeting POLE2 Creates a Novel Vulnerability in Renal Cell Carcinoma via Modulating Stanniocalcin 1.

Front Cell Dev Biol 2021 11;9:622344. Epub 2021 Feb 11.

Department of Urology, Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: The aim of this study is to investigate the biological functions and the underlying mechanisms of DNA polymerase epsilon subunit 2 (POLE2) in renal cell carcinoma (RCC).

Methods: The datasets of POLE2 expression in The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) and International Cancer Genome Consortium (ICGC) databases was selected and the correlation between POLE2 and various clinicopathological parameters was analyzed. The POLE2 expression in RCC tissues was examined by immunohistochemistry. The POLE2 knockdown cell lines were constructed. and experiments were carried out to investigate the function of POLE2 on cellular biology of RCC, including cell viability assay, clone formation assay, flow cytometry, wound-healing assay, Transwell assay, qRT-PCR, Western blot, etc. Besides, microarray, co-immunoprecipitation, rescue experiment, and Western blot were used to investigate the molecular mechanisms underlying the functions of POLE2.

Results: POLE2 was overexpressed in RCC tissues, and high expression of POLE2 was correlated with poor prognosis of RCC. Furthermore, knockdown of POLE2 significantly inhibited cell proliferation, migration, and facilitated apoptosis . experiments revealed that POLE2 attenuated RCC tumorigenesis and tumor growth. we also illuminated that stanniocalcin 1 (STC1) was a downstream gene of POLE2, which promoted the occurrence and development of RCC. Besides, knockdown of POLE2 significantly upregulated the expression levels of Bad and p21 while the expression levels of HSP70, IGF-I, IGF-II, survivin, and sTNF-R1 were significantly downregulated. Western blot analysis also showed that knockdown of POLE2 inhibited the expression levels of Cancer-related pathway proteins including p-Akt, CCND1, MAPK9, and PIK3CA.

Conclusion: Knockdown of POLE2 attenuates RCC cells proliferation and migration by regulating STC1, suggesting that POLE2-STC1 may become a potential target for RCC therapy.
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http://dx.doi.org/10.3389/fcell.2021.622344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905105PMC
February 2021

Evolution and roles of cytokinin genes in angiosperms 1: Do ancient IPTs play housekeeping while non-ancient IPTs play regulatory roles?

Hortic Res 2020 Mar 1;7(1):28. Epub 2020 Mar 1.

State Key Laboratory of Crop Genetics and Germplasm Enhancement and the College of Horticulture, Nanjing Agricultural University, Nanjing, P. R. China.

Isopentenyltransferase (IPT) genes, including those encoding ATP/ADP-IPTs and tRNA-IPTs, control the rate-limiting steps of the biosynthesis of N-(Δ-isopentenyl)adenine (iP)-type and trans-zeatin (tZ)-type cytokinins and cis-zeatin (cZ)-type cytokinins, respectively. However, the evolution and roles of these IPTs in angiosperms are not well understood. Here, we report comprehensive analyses of the origins, evolution, expression patterns, and possible roles of ATP/ADP-IPTs and tRNA-IPTs in angiosperms. We found that Class I and II tRNA-IPTs likely coexisted in the last common ancestor of eukaryotes, while ATP/ADP-IPTs likely originated from a Class II tRNA-IPT before the divergence of angiosperms. tRNA-IPTs are conservatively retained as 2-3 copies, but ATP/ADP-IPTs exhibit considerable expansion and diversification. Additionally, tRNA-IPTs are constitutively expressed throughout the plant, whereas the expression of ATP/ADP-IPTs is tissue-specific and rapidly downregulated by abiotic stresses. Furthermore, previous studies and our present study indicate that ATP/ADP-IPTs and their products, iPs/tZs, may regulate responses to environmental stresses and organ development in angiosperms. We therefore hypothesize that tRNA-IPTs and the associated cZs play a housekeeping role, whereas ATP/ADP-IPTs and the associated iP/tZ-type cytokinins play regulatory roles in organ development and stress responses in angiosperms, which echoes the conclusions and hypothesis presented in the accompanying study by Wang, X. et al Evolution and roles of cytokinin genes in angiosperms 2: Do ancient CKXs play housekeeping roles while non-ancient CKXs play regulatory roles? Hortic Res https://doi.org/10.1038/s41438-020-0246-z.
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http://dx.doi.org/10.1038/s41438-019-0211-xDOI Listing
March 2020

Evolution and roles of cytokinin genes in angiosperms 2: Do ancient CKXs play housekeeping roles while non-ancient CKXs play regulatory roles?

Hortic Res 2020 Mar 1;7(1):29. Epub 2020 Mar 1.

State Key Laboratory of Crop Genetics and Germplasm Enhancement and College of Horticulture, Nanjing Agricultural University, Nanjing, P. R. China.

Cytokinin oxidase/dehydrogenase (CKX) is a key enzyme responsible for the degradation of endogenous cytokinins. However, the origins and roles of CKX genes in angiosperm evolution remain unclear. Based on comprehensive bioinformatic and transgenic plant analyses, we demonstrate that the CKXs of land plants most likely originated from an ancient chlamydial endosymbiont during primary endosymbiosis. We refer to the CKXs retaining evolutionarily ancient characteristics as "ancient CKXs" and those that have expanded and functionally diverged in angiosperms as "non-ancient CKXs". We show that the expression of some non-ancient CKXs is rapidly inducible within 15 min upon the dehydration of Arabidopsis, while the ancient CKX (AtCKX7) is not drought responsive. Tobacco plants overexpressing a non-ancient CKX display improved oxidative and drought tolerance and root growth. Previous mutant studies have shown that non-ancient CKXs regulate organ development, particularly that of flowers. Furthermore, ancient CKXs preferentially degrade cis-zeatin (cZ)-type cytokinins, while non-ancient CKXs preferentially target N-(Δ-isopentenyl) adenines (iPs) and trans-zeatins (tZs). Based on the results of this work, an accompanying study (Wang et al. https://doi.org/10.1038/s41438-019-0211-x) and previous studies, we hypothesize that non-ancient CKXs and their preferred substrates of iP/tZ-type cytokinins regulate angiosperm organ development and environmental stress responses, while ancient CKXs and their preferred substrates of cZs play a housekeeping role, which echoes the conclusions and hypothesis described in the accompanying report (Wang, X. et al. Evolution and roles of cytokinin genes in angiosperms 1: Doancient IPTs play housekeeping while non-ancient IPTs play regulatory roles? Hortic Res 7, (2020). https://doi.org/10.1038/s41438-019-0211-x).
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http://dx.doi.org/10.1038/s41438-020-0246-zDOI Listing
March 2020

Treatment of a Young Maxillary Central Incisor with Two Root Canals: A Case Report.

Int J Gen Med 2021 11;14:419-423. Epub 2021 Feb 11.

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.

Currently, the common treatment for pulpitis and periapical diseases is root canal treatment. However, the complex variations of root canal system often affect the effect of root canal treatment and even lead to treatment failure. Therefore, it is of great significance for dentists to emphasize the diversity of root canal morphology and to be familiar with the anatomical morphology of root canal to improve the success rate of clinical diagnosis and treatment. We reported a case of an eight-year-old female patient of type V root canal in a young maxillary middle incisor. The young maxillary central incisor was diagnosed with irreversible pulpitis by radiography and CBCT examination. The present case report described the entire treatment procedure of a young maxillary central incisor after trauma, including successive apical examination, CBCT examination and multiple root canal filling, and finally the treatment was completed with the aid of microscope. The root canals were filled with the vertical compression technique. Z350 composite resin was used to repair the tooth. The patient was followed-up at three, six, and 12 months after endodontic treatment. All of the examinations were normal. Finding the anatomical configuration of root canal by various ways will help to improve the success rate of root canal therapy.
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http://dx.doi.org/10.2147/IJGM.S292603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886291PMC
February 2021

Comparison of different groundwater vulnerability evaluation models of typical karst areas in north China: a case of Hebi City.

Environ Sci Pollut Res Int 2021 Feb 16. Epub 2021 Feb 16.

School of Environmental Studies, China University of Geosciences, Wuhan, 430074, China.

Groundwater pollution is a serious problem in north China. However, the study on the vulnerability of karst groundwater is mainly in south China, and there are few studies in north China. To study the applicability of different models of karst areas in north China, this paper chose a special study area-Hebi City, where the exposed karst area is widely developed in the hilly area, but the covered karst area is in the eastern part of the study area. The DRASTIC model, the AHP-DRASTIC model, and the improved COPK model were adopted to evaluate the vulnerability of shallow karst groundwater in Hebi City. Cl, SO, NO, and TDS were selected to verify the rationality of the evaluation results. It shows that the improved COPK model is more suitable for the shallow karst groundwater vulnerability evaluation in the karst areas in northern China represented by the study area than the other two. The study area was divided into 4 classes by the improved COPK model: highest (14.07%), high (53.05%), low (21.37%), and lowest (11.51%). Then, the analytic hierarchy process and comprehensive index model were used to evaluate the groundwater pollution load intensity, and the study area was divided into 3 classes: high (23.33%), moderate (64.66%), and low (12.01%). According to the analysis of the relationship between groundwater pollution load intensity and groundwater quality, it can be found that human activities have an obvious influence on groundwater quality in the study area. Finally, combined with human activities, the study area was divided into 3 remediation areas, 1 control area, and 1 protected area. This paper can provide a scientific basis for rational exploitation and utilization of groundwater resources. It can also provide a reference for future generations to evaluate the groundwater vulnerability in the northern China karst areas.
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http://dx.doi.org/10.1007/s11356-021-12719-xDOI Listing
February 2021

Polymer-based hydrogels with local drug release for cancer immunotherapy.

Biomed Pharmacother 2021 May 8;137:111333. Epub 2021 Feb 8.

Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease; Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233000, China. Electronic address:

Immunotherapy that boosts the body's immune system to treat local and distant metastatic tumors has offered a new treatment option for cancer. However, cancer immunotherapy via systemic administration of immunotherapeutic agents often has two major issues of limited immune responses and potential immune-related adverse events in the clinic. Hydrogels, a class of three-dimensional network biomaterials with unique porous structures can achieve local delivery of drugs into tumors to trigger the antitumor immunity, resulting in amplified immunotherapy at lower dosages. In this review, we summarize the recent development of polymer-based hydrogels as drug release systems for local delivery of various immunotherapeutic agents for cancer immunotherapy. The constructions of polymer-based hydrogels and their local delivery of various drugs in tumors to achieve sole immunotherapy, and chemotherapy-, and phototherapy-combinational immunotherapy are introduced. Furthermore, a brief conclusion is given and existing challenges and further perspectives of polymer-based hydrogels for cancer immunotherapy are discussed.
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http://dx.doi.org/10.1016/j.biopha.2021.111333DOI Listing
May 2021

Large-area integration of two-dimensional materials and their heterostructures by wafer bonding.

Nat Commun 2021 Feb 10;12(1):917. Epub 2021 Feb 10.

Division of Micro and Nanosystems, School of Electrical Engineering and Computer Science, KTH Royal Institute of Technology, Stockholm, Sweden.

Integrating two-dimensional (2D) materials into semiconductor manufacturing lines is essential to exploit their material properties in a wide range of application areas. However, current approaches are not compatible with high-volume manufacturing on wafer level. Here, we report a generic methodology for large-area integration of 2D materials by adhesive wafer bonding. Our approach avoids manual handling and uses equipment, processes, and materials that are readily available in large-scale semiconductor manufacturing lines. We demonstrate the transfer of CVD graphene from copper foils (100-mm diameter) and molybdenum disulfide (MoS) from SiO/Si chips (centimeter-sized) to silicon wafers (100-mm diameter). Furthermore, we stack graphene with CVD hexagonal boron nitride and MoS layers to heterostructures, and fabricate encapsulated field-effect graphene devices, with high carrier mobilities of up to [Formula: see text]. Thus, our approach is suited for backend of the line integration of 2D materials on top of integrated circuits, with potential to accelerate progress in electronics, photonics, and sensing.
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http://dx.doi.org/10.1038/s41467-021-21136-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876008PMC
February 2021

Synthesis and anti-rheumatoid arthritis activities of 3-(4-aminophenyl)-coumarin derivatives.

J Enzyme Inhib Med Chem 2021 Dec;36(1):450-461

Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

Rheumatoid arthritis is a chronic systemic disease characterised by an unknown aetiology of inflammatory synovitis. A large number of studies have shown that synoviocytes show tumour-like dysplasia in the pathological process of RA, and the changes in the expression of related cytokines are closely related to the pathogenesis of RA. In this thesis, a series of novel 3-(4-aminophenyl) coumarins containing different substituents were synthesised to find new coumarin anti-inflammatory drugs for the treatment of rheumatoid arthritis. The results of preliminary activity screening showed that compound had the strongest inhibitory activity on the proliferation of fibroid synovial cells, and it also had inhibitory effect on RA-related cytokines IL-1, IL-6, and TNF-α. The preliminary mechanism study showed that compound could inhibit the activation of NF-κB and MAPKs signal pathway. The anti-inflammatory activity of compound was further determined in the rat joint inflammation model.
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http://dx.doi.org/10.1080/14756366.2021.1873978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889190PMC
December 2021

Analysis and review of trichomes in plants.

BMC Plant Biol 2021 Feb 1;21(1):70. Epub 2021 Feb 1.

Key laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Guizhou University, Guiyang, Guizhou, People's Republic of China.

Background: Trichomes play a key role in the development of plants and exist in a wide variety of species.

Results: In this paper, it was reviewed that the structure and morphology characteristics of trichomes, alongside the biological functions and classical regulatory mechanisms of trichome development in plants. The environment factors, hormones, transcription factor, non-coding RNA, etc., play important roles in regulating the initialization, branching, growth, and development of trichomes. In addition, it was further investigated the atypical regulation mechanism in a non-model plant, found that regulating the growth and development of tea (Camellia sinensis) trichome is mainly affected by hormones and the novel regulation factors.

Conclusions: This review further displayed the complex and differential regulatory networks in trichome initiation and development, provided a reference for basic and applied research on trichomes in plants.
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http://dx.doi.org/10.1186/s12870-021-02840-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852143PMC
February 2021

Enhancing biochar sorption properties through self-templating strategy and ultrasonic fore-modified pre-treatment: Characteristic, kinetic and mechanism studies.

Sci Total Environ 2021 May 9;769:144574. Epub 2021 Jan 9.

Ministry of Education Key Laboratory of Ecology and Resource Use of the Mongolian Plateau & Inner Mongolia Key Laboratory of Environmental Pollution Control and Waste Resource Recycle, School of Ecology and Environment, Inner Mongolia University, Hohhot 010021, China. Electronic address:

The traditional anaerobic sewage treatment facilities are unsuitable for the widely uncontrolled spread of antibiotic residues in hospital or on livestock farm, which have raised the risk levels of high concentrations of antibiotic residues leakages and seriously threatened the aquatic ecology safeties. Thus, to develop an effective adsorbent with safe, low cost, and high firmly adsorptive capacity are imminent required. In this investigated, a self-templating hydrothermal alkali fore-modified & ultrasonic treatment was developed to achieve the highly adsorptive capacity and low desorption rate of biochar. As expected, the prepared biochar adsorbents present plenty of surface functional groups and micro pores. The BET value is raised up 1452 cm·g for biochar treated by the associated alkali fore-modified and ultrasonic treatment (UFB), whereas it is only 415.8 cm·g for the biochar treated by traditional carbonization (AC) and 1205 cm·g for the biochar by further hydrothermal alkali fore-modification (FB). Congruously, UFB exhibits the removal abilities of 397.70 mg·g of levofloxacin (LEV) and 320.99 mg·g of chlorotetracycline (CTC), 3.5-6.3 times absorbability towards familiar antibiotics than traditional biochar. Moreover, the corresponding the lowest desorption of 1.30 mg·g (LEV) and 0.43 mg·g (CTC) mg·g by UFB have been confirmed. Meanwhile, Furthermore, both the adsorption and desorption mechanisms have been addressed by kinetic studies, pore width distributions, XPS and FTIR surveys. It is proposed the fore-modified treatment is more helpful for carbon functionalization while the ultrasonic treatment dedicates to the largely microporous structures. Consequently, the adsorption's capacity and stability of UFB adsorbents is large promoted due to its more micro- and meso-porous structure through a jointly hydrothermal alkali fore-modified and ultrasonic treatment. The present investigation will provide a novel alternative preparation strategy of the highly efficient adsorbent for emergency medical wastewater treatment.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144574DOI Listing
May 2021

Overexpression of the wheat NAC transcription factor TaSNAC4-3A gene confers drought tolerance in transgenic Arabidopsis.

Plant Physiol Biochem 2021 Mar 7;160:37-50. Epub 2021 Jan 7.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling, 712100, Shaanxi, China. Electronic address:

NAC transcription factors (TFs) play critical roles in plant abiotic stress responses. However, information on the roles of NAC TFs is limited in wheat (Triticum aestivum L.). In this study, we isolated three wheat TaSNAC4 homeologous genes, TaSNAC4-3A, TaSNAC4-3B, and TaSNAC4-3D, and characterized the function of TaSNAC4-3A in plant drought tolerance. TaSNAC4 is highly expressed in seedling leaves, and expression is induced by various abiotic stresses. Transient expression and transactivation assays showed that TaSNAC4-3A is localized to the nucleus, and the C-terminal region has transcriptional activation activity. Overexpression of TaSNAC4-3A in Arabidopsis led to stimulated germination and root growth when exposed to salt and osmotic stresses, and drought stress tolerance was significantly increased in the TaSNAC4-3A transgenic lines. When compared to the control plants, the transgenic lines overexpressing TaSNAC4-3A exhibited reduced stomatal aperture size under drought stress, and therefore had lower water loss rates. In addition, the overexpression of TaSNAC4-3A led to abscisic acid (ABA) hypersensitivity at the root elongation and seed germination stages. Further transcriptomic analysis demonstrated that there was a significant up-regulation of stress responsive genes in the TaSNAC4-3A transgenic lines. Our findings have revealed the important role of TaSNAC4-3A in plant drought tolerance.
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http://dx.doi.org/10.1016/j.plaphy.2021.01.004DOI Listing
March 2021

Localized increases in CEPT1 and ATGL elevate plasmalogen phosphatidylcholines in HDLs contributing to atheroprotective lipid profiles in hyperglycemic GCK-MODY.

Redox Biol 2021 Apr 6;40:101855. Epub 2021 Jan 6.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China. Electronic address:

Glucokinase-maturity onset diabetes of the young (GCK-MODY) represents a rare genetic disorder due to mutation in the glucokinase (GCK) gene. The low incidence of vascular complications in GCK-MODY makes it a natural paradigm for interrogating molecular mechanisms promoting vascular health under prolonged hyperglycemia. Clinical rate of misdiagnosis has remained high, and a reliable serum lipid biomarker that precedes genetic screening can facilitate correct diagnosis and treatment. Herein, we comprehensively quantitated 565 serum lipids from 25 classes in 105 subjects (42 nondiabetic controls, 30 GC K-MODY patients, 33 drug-naïve, and newly-onset T2D patients). At false-discovery rate (FDR) < 0.05, several phosphatidylcholines (PCs) and plasmalogen PCs were specifically increased in GCK-MODY, while triacylglycerols (TAGs) and diacylglycerols (DAGs) were reduced. Correlation matrices between lipids uncovered coregulation between plasmalogen PCs (PCps) and glycerolipid precursors was distinctly enhanced in GCK-MODY compared to T2D. Strengthened positive correlations between serum PCps and circulating HDLs was specifically observed in hyperglycemic subjects (i.e. T2D and GCK-MODY) compared to normglycemic controls, suggesting that HDL-PCps may elicit distinct physiological effects under hyperglycemia. Amongst GCK-MODY patients, individuals harboring variants of GCK mutations with elevated PCps also exhibited higher HDLs. Isolated HDLs displayed localized increases (p < 0.05) in very-long-chain PUFA-PCs and PCps in GCK-MODY. Protein analyses revealed elevated levels of HDL-resident ATGL (P = 0.003) and CEPT1 (P < 0.0001), which mediate critical steps of PCps production along the TAG-DAG-PC axis, in GCK-MODY relative to T2D. A panel of four lipids differentiated GCK-MODY from T2D with AUC of 0.950 (95% CI 0.903-9.997). This study provides the first evidence that enhanced recruitment of CEPT1 and ATGL onto HDLs essentially underlie the atheroprotective profiles associated with GCK-MODY. Resultant increases in the production of HDL-PCps and PUFA-PCs provides an active, circulating form of protection towards the vasculature of GCK-MODY, thereby lowering the incidence of vascular complications despite chronic exposure to hyperglycemia since birth.
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http://dx.doi.org/10.1016/j.redox.2021.101855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810764PMC
April 2021

The vessel density of the superficial retinal capillary plexus as a new biomarker in cerebral small vessel disease: an optical coherence tomography angiography study.

Neurol Sci 2021 Jan 11. Epub 2021 Jan 11.

Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.

Background: Optical coherence tomography angiography (OCTA) is a novel and noninvasive technique for the quantitative assessment of retinal microvascular perfusion. Since the retinal and cerebral small vessels share similar embryological origins, anatomical features, and physiological properties, altered retinal microvasculature might provide a new perspective on the mechanisms of cerebral small vessel disease (CSVD).

Objective: We aimed to evaluate retinal vessel density (VD) in patients with CSVD using OCTA and identify associations with cerebral magnetic resonance imaging (MRI) markers and cognitive function.

Methods: We prospectively recruited 47 CSVD patients and 30 healthy controls (HCs) to participate in the study. All participants underwent OCTA to evaluate retinal microvascular perfusion. The VDs of the macular region in the superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and foveal avascular zone (FAZ) were determined, along with the VD of the optic nerve head (ONH) in the radial peripapillary capillary (RPC) network. Additionally, cerebral MRI and cognitive function tests were performed.

Results: In the macula area, the VD of the CSVD patients was significantly lower than HCs in the temporal quadrant of SRCP. In the ONH area, CSVD patients had lower VD than HCs in the peripapillary RPC network. According to multiple linear regression analysis, decreased VD of the macular SRCP was associated with white matter hyperintensity scores after adjustment for age, hypertension, diabetes, and hyperlipidemia. Furthermore, the VD of the macular SRCP was significantly correlated with CSVD patients' cognitive function, especially global cognition, memory function, attention function, information processing, and executive function.

Conclusion: OCTA revealed a significant decrease in retinal microvascular perfusion in CSVD patients, and retinal hypoperfusion was related to MRI markers and cognitive function, suggesting that these parameters could have potential utility as early disease biomarkers.
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http://dx.doi.org/10.1007/s10072-021-05038-zDOI Listing
January 2021

The Retinal Vessel Density Can Reflect Cognitive Function in Patients with Alzheimer's Disease: Evidence from Optical Coherence Tomography Angiography.

J Alzheimers Dis 2021 ;79(3):1307-1316

Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: There is increasing evidence that Alzheimer's disease (AD) patients may present decreased cerebral blood perfusion before pathological brain changes. Using the retina as a window to the brain, we can study disorders of the central nervous system through the eyes.

Objective: This study aimed to investigate differences in retinal structure and vessel density (VD) between patients with mild AD and healthy controls (HCs). Furthermore, we explored the relationship between retinal VD and cognitive function.

Methods: We enrolled 37 patients with AD and 29 age-matched HCs who underwent standard ophthalmic optical coherence tomography angiography (OCTA) for evaluation of the retinal layer thickness and VD parameters. Cognitive function was evaluated using a battery of neuropsychological assessments. Finally, the correlations among retinal layer thickness, VD parameters, and cognitive function were evaluated.

Results: The retinal fiber layer thickness and retinal VD of patients with AD were significantly reduced compared with HCs. The retinal VD was significantly correlated with overall cognition, memory, executive, and visual-spatial perception functions. However, there was no significant between-group difference in the macular thickness.

Conclusion: Our findings indicate a positive correlation between retinal VD and some, but not all, cognitive function domains. Most importantly, we demonstrated the role of OCTA in detecting early capillary changes, which could be a noninvasive biomarker for early AD.
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http://dx.doi.org/10.3233/JAD-200971DOI Listing
January 2021

Microstructure and interfacial metallurgical bonding of 1Cr17Ni2/carbon steel extreme high-speed laser cladding coating.

Adv Compos Hybrid Mater 2021 Jan 4:1-7. Epub 2021 Jan 4.

Zhenjiang Haili New Material Technology Co., Ltd, Zhenjiang, 212000 China.

The extreme high-speed laser cladding (EHLA) was employed to fabricate a 1Cr17Ni2 coating. The solidification behavior, phase transformation, and interfacial metallurgical bonding of the coating were systematically investigated. The results showed that the major phase transformation during solidification was liquid to γ-Fe. The large temperature gradient of melting pool and slow grow rate of γ-Fe grain contributed to the fine columnar prior austenite grain (PAG) in coating. The largest thermal conductivity of [0 0 1] crystal direction determined the preferential [0 0 1] orientation of PAG perpendicular to the liquid-solid interface. A thin γ-Fe layer (approximately 5 μm) was observed between coating and substrate. The Bain relationship between interfacial γ-Fe layer and substrate and the K-S relationship between interfacial γ-Fe layer and coating contributed to the reliable metallurgical bonding between coating and substrate. The shear test revealed the high shear strength (approximately 92% of that of substrate) and weaker plastic deformation ability of the interface. The interfacial γ-Fe layer effectively combined the coating and substrate via K-S and Bain crystallographic relationship.
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http://dx.doi.org/10.1007/s42114-020-00194-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780920PMC
January 2021

Direct separation and purification of α-lactalbumin from cow milk whey by aqueous two-phase flotation of thermo-sensitive polymer/phosphate.

J Sci Food Agric 2021 Jan 8. Epub 2021 Jan 8.

College of Food Science, Northeast Agricultural University, Harbin, China.

Background: α-lactalbumin (α-La) is of great interest to the industry as a result of its excellent functional properties and nutritional value. Aqueous two-phase flotation (ATPF) of thermo-sensitive polymer poly (ethylene glycol-ran-propylene glycol) monobutyl ether (UCON) and KH PO was applied to directly separate and purify α-La from milk whey, which was purposed to simplify the production process and reduced cost of production.

Results: The effect of ATPF composition and operating parameters on the flotation efficiency (E) and purity of α-La were investigated. The optimal conditions included 2 min of premixing time, 30 mL min flow velocity and 20 min of flotation time, whereas the composition conditions comprised 35.0 mL 0.18 g mL phosphate solution (containing 10% (cow milk whey/salt solution, v/v) cow milk whey, 50 ppm defoamer and 2 g NaCl) and 5.0 mL of 40% (w/w) UCON solution. Under the optimal conditions, E of α-La was 95.67 ± 1.04% and purity of α-La was 98.78 ± 1.19%. UCON was recovered by a thermally-induced phase separation and reused in next ATPF process without reducing E of α-La. Purified α-La was characterized by several key technologies. The results indicated that α-La in cow milk whey could be directly separated and purified by the ATPF and the purity was satisfactory. Moreover, it was suggested there was no obvious structure difference between the α-La separated by ATPF and the α-La standard.

Conclusion: The present study enabled the recycling of UCON, providing an effective, economically viable and environmentally friendly approach for the separation and purification of protein. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11055DOI Listing
January 2021