Publications by authors named "Huimin Li"

275 Publications

Renovation priorities for old residential districts based on resident satisfaction: An application of asymmetric impact-performance analysis in Xi'an, China.

PLoS One 2021 22;16(7):e0254372. Epub 2021 Jul 22.

School of Management, Xi'an University of Architecture and Technology, Xi'an, China.

China is currently designing a regional economic layout for high-quality urban development, shifting its focus from the primary stage of beautifying cities to the next stage of profound urbanization aiming at strengthening industry. This is of high importance given that the urbanization rate of permanent residents by the end of 2019 was 60.60%, according to the National Bureau of Statistics of China. In the face of various factors such as the need to economize the intensive use of resources, urban stock development, and the need for urban constructions to maintain harmony with the surrounding ecosystem, regeneration has emerged as an efficient means to repurpose old residential districts. It conforms to the policy of stock planning and is one of the important methods to ensure the sustainable development of a city. Prioritizing the right attributes in renovation is one of the critical steps in the regeneration of old residential districts-instead of merely focusing on their selection and scoring by experts, more attention should be paid to the resident satisfaction (or the lack thereof) arising from them. Therefore, in this study, we have proposed a collaborative approach that requires communities to prioritize the appropriate aspects in urban renewal. This study employed the three-factor theory of customer satisfaction, to investigate the five attributes namely geographical location, infrastructure, traffic, residential management, and living facilities, of satisfaction and dissatisfaction of residents in the old city. This includes 327 samples based on the residents of Yanta old town in Xi'an. The asymmetric impact-performance analysis technique was used to explore, and quantify the asymmetric relationship between the attributes of old residential districts, and residents' satisfaction. The results proved that attributes were divided into three: excitement factors, performance, and basic factors, based on the asymmetric influence of attributes on residents' satisfaction. Residential management was into excitement factors, living facilities were categorized into basic factors, and the remaining three attributes were categorized into performance factors. The satisfaction of the residents regarding the renovation was maximized by comprehensively considering the performance of given attributes, adjusting the improvement strategies of each attribute, and further determining the focus of the renovation of the old residential districts. Simultaneously, it helped planners make more rational choices in urban renewal and sustainable development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254372PLOS
July 2021

Value assessment for the restoration of industrial relics based on analytic hierarchy process: a case study of Shaanxi Steel Factory in Xi'an, China.

Environ Sci Pollut Res Int 2021 Jul 21. Epub 2021 Jul 21.

Xi'an High-tech Hard Technology Industry Investment Holding Group Co., Ltd., Xi'an, 710038, China.

Concomitant with the promotion of industrial transformation, sustainable development strategies, and accelerated urbanization, there has been an increase in the number of industrial relic restoration projects. However, there are many disputes over the value and development of such industrial relic restoration projects. In this work, we identified three evaluation indicators based on a study of 106 industrial relic restoration projects in China. A value assessment model composed of five parts combining the Delphi method and analytic hierarchy process was established. The results show that an effective assessment of the value of industrial relic restoration projects can enable the effective use of green technology, reduce construction costs, protect industrial heritage, and inherit historical culture. In addition, there are many uncertain factors in developing these projects, such as brownfield pollution and dilapidated buildings, and appropriate renewal strategies can reduce safety risks as well as maximize the heritage value. As there is limited research assessing the value of industrial relic restoration projects in China, our study can serve as a reference for the value assessment of existing building restoration projects including historical blocks and livable villages.
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http://dx.doi.org/10.1007/s11356-021-14897-0DOI Listing
July 2021

Claudin-7 deficiency promotes stemness properties in colorectal cancer through Sox9-mediated Wnt/β-catenin signalling.

J Transl Med 2021 Jul 19;19(1):311. Epub 2021 Jul 19.

Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.

Background: Colorectal cancer (CRC) is a common malignant tumour of the digestive tract that is characterized by high patient morbidity and mortality rates. Claudin-7 (Cldn7), a tight junction protein, was recently reported to function as a candidate tumour suppressor gene in CRC. Our previous study demonstrated that the large intestine of C57/BL6 mice showed intestinal adenomas and abnormal Ki67 expression and distribution in the intestinal crypt when Cldn7 was knocked out. The aim of this study was to further investigate whether Cldn7 deficiency has non-tight junction functions, affects intestinal stemness properties, promotes CRC and to determine the specific mechanism.

Methods: Cell proliferation assays, migration assays, apoptosis assays, tumour sphere formation assays in vitro, and subcutaneous xenograft models in vivo were used to determine the effects of Cldn7 knockdown on the biological characteristics of CRC stem cells. Western blotting, qPCR and immunofluorescence staining were performed to identify the epithelial-mesenchymal transition and the activation of Wnt/β-catenin pathway in CRC stem cells. Cldn7 inducible conditional gene knockout mice and immunohistochemical staining further verified this hypothesis in vivo. The mechanism and target of Cldn7 were determined by performing a chromatin immunoprecipitation (ChIP) assay and coimmunoprecipitation (CoIP) assay.

Results: Cldn7 knock down in CRC stem cells promoted cell proliferation, migration, and globular growth in serum-free medium and the ability to form xenograft tumours; cell apoptosis was inhibited, while the cellular epithelial-mesenchymal transition was also observed. These changes in cell characteristics were achieved by activating the Wnt/β-catenin pathway and promoting the expression of downstream target genes after β-catenin entry into the nucleus, as observed in CRC cell lines and Cldn7 gene knockout mouse experiments. Using ChIP and CoIP experiments, we initially found that Cldn7 and Sox9 interacted at the protein level to activate the Wnt/β-catenin pathway.

Conclusions: Based on our research, Cldn7 deficiency confers stemness properties in CRC through Sox9-mediated Wnt/β-catenin signalling. This result clarifies that Cldn7 plays an inhibitory role in CRC and reveals a possible molecular mechanism, which is conducive to further research on Cldn7 and cancer stem cells.
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http://dx.doi.org/10.1186/s12967-021-02983-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287764PMC
July 2021

Clinical significance of interventional therapeutic bronchoscopy combined with bronchial arterial embolization in the treatment of hypervascular primary airway tumors in children.

Pediatr Investig 2021 Jun 18;5(2):130-135. Epub 2021 Jun 18.

The Second Department of Respiratory Medicine Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Importance: Pediatric hypervascular primary airway tumors are progressive, fatal lesions with a low incidence, and the disease is often more serious than that in adults.

Objective: To evaluate the clinical efficacy and safety of interventional therapeutic bronchoscopy combined with conservative treatment and bronchial arterial embolization in children with primary airway tumors.

Methods: We retrospectively analyzed the clinical data of four pediatric patients with hypervascular primary airway tumor between 2017 and 2019 at Beijing Children's Hospital.

Results: Two patients were low-grade bronchial mucoepidermoid carcinoma, one patient was pleomorphic adenoma, and one was bronchial leiomyoma. Interventional therapeutic bronchoscopy combined with bronchial arterial embolization was used for treatment (all four patients received general anesthesia). The tumors were safely resected in all patients via interventional bronchoscopy. There were no severe complications related to the procedures. All patients were followed up for 5-12 months, and one low-grade bronchial mucoepidermoid carcinoma recurred.

Interpretation: Interventional therapeutic bronchoscopy combined with bronchial arterial embolization appears to be a safe and efficient therapeutic method associated with less trauma and fewer complications, including no serious adverse events, in children with hypervascular primary airway tumors without bronchus wall infiltration.
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http://dx.doi.org/10.1002/ped4.12256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212720PMC
June 2021

Correlative investigation between routine clinical parameters of dual-energy computed tomography and the outcomes of extracorporeal shock wave lithotripsy in children with urolithiasis: a retrospective study.

Abdom Radiol (NY) 2021 Jun 10. Epub 2021 Jun 10.

Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China.

Purpose: To evaluate the associations of DECT parameters with extracorporeal shock wave lithotripsy (ESWL) outcomes in pediatric patients.

Methods: A retrospective study of consecutive patients with calculi who underwent ESWL and DECT in our hospital was performed in 2011-2019. The primary outcome was DECT imaging's correlation with ESWL outcomes. The secondary outcome was to determine DECT parameters independently predicting ESWL outcomes, including stone-free (SF) and residual stone (RS) statuses.

Results: The study included 207 patients. The mean CT attenuations at 140 kVp, 80 kVp, and 120 kVp and effective atomic number (Zeff) were significantly correlated with stone free (SF) and residual stone (RS) (P < 0.05). Areas under the curves (AUCs) of CT attenuations at 120 kVp, 80 kVp, 140 kVp, and dual-energy index (DEI) were 0.784 (95% CI 0.672-0.897), 0.780 (95% CI 0.677-0.884), 0.766 (95% CI 0.658-0.885), and 0.709 (95% CI 0.578-0.840) (all P < 0.05). With cutoffs of 882.5, 1330.5, 1042.5, and 0.103 for CT attenuations at 140 kVp, 80 kVp, 120 kVp, and DEI, respectively, sensitivities and specificities were 75.0% and 31.1%, 83.3% and 31.8%, 80.3% and 31.1%, and 58.3% and 44.7%, respectively.

Conclusion: Our results demonstrated that the parameters of DECT could be used to predict ESWL outcomes (especially the SF status) in children with urolithiasis. ESWL success can be accurately predicted by DECT, and it is hard to predict ESWL failure.
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http://dx.doi.org/10.1007/s00261-021-03162-0DOI Listing
June 2021

Study on the Immune Escape Mechanism of Acute Myeloid Leukemia With DNMT3A Mutation.

Front Immunol 2021 20;12:653030. Epub 2021 May 20.

Department of Hematology, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mutated acute myeloid leukemia (AML) has a poor prognosis, but the exact mechanism is still unclear. Here, we aimed to explore the mechanism of immune escape in AML with DNMT3A mutation. We constructed a DNMT3A knockout clone and DNMT3A-R882H-mutated clones. RNA-seq results showed that transcription factors and macrophage inflammatory proteins were significantly downregulated in the DNMT3A mutant clones. KEGG enrichment and gene set enrichment analysis (GSEA) showed that a large number of genes were enriched in inflammatory immune-related pathways, such as the toll-like receptor signaling pathway. Therefore, we co-cultured AML cells with macrophages. The DNMT3A-mutated AML cells attenuated M1 macrophage polarization and resisted its killing effect and . In xenografts, the tumor volumes in the experimental group were significantly larger than those in the control group, and the proportion of M2 macrophages was significantly higher. After the co-culture, the increase in pro-inflammatory cytokine expression in the mutant cells was significantly lower than that in the control group, while that in immunosuppressive factors was not significantly different. In co-cultivated supernatants, the concentration of inflammatory factors in the experimental group was significantly lower than that in the control group, while that of immunosuppressive factors was significantly higher. Resistin significantly promoted the expression of inflammatory proteins in AML cells. It relieved the inhibitory effect of DNMT3A mutation, promoted the phenotypic recovery of the co-cultured macrophages, eliminated resistance, and regulated the immune microenvironment. Thus, resistin may serve as an ancillary drug for patients with DNMT3A-mutated AML.
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http://dx.doi.org/10.3389/fimmu.2021.653030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173207PMC
May 2021

Comparative analysis of tuberous root metabolites between cultivated and wild varieties of Rehmannia glutinosa by widely targeted metabolomics.

Sci Rep 2021 Jun 1;11(1):11460. Epub 2021 Jun 1.

College of Life Sciences, Henan Normal University, Xinxiang, 453007, Henan, People's Republic of China.

Differential metabolites between tuberous roots from cultivated variety (ZP) and wild variety (YS) of Rehmannia glutinosa were analyzed by widely targeted metabolomics, and annotated to KEGG pathways. 228 secondary metabolites (SM) in ZP and YS were detected, of which 58 were differential metabolites (DM), including 41 flavonoids, 10 phenolic acids, 3 terpenoids, 2 alkaloids and 2 others, and 170 were unchanged; Among 58 DMs, 44 (75.9%) were up-regulated in YS, of which 30 were unique to YS, while 14 (24.1%) were down-regulated in YS, of which 10 were unique to ZP; Among flavonoids, 33 (80.5%) were more highly expressed in YS than in ZP; Among phenolic acids, 7 (70%) were more highly expressed in YS than in ZP; 12 of 58 DMs were annotated into 17 types of KEGG pathways. Among them, benzoic acid and p-Coumaryl alcohol were up-regulated in YS, and annotated into 10 pathways (58.8%) and 4 pathways (23.5%), respectively. In addition, much of DMs possess various pharmacological effects. These results indicated better quality of YS than ZP and the necessity of YS domestication. Taken together, this study will provide a reference for the scientific introduction, comprehensive development and utilization of wild Rehmannia glutinosa.
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http://dx.doi.org/10.1038/s41598-021-90961-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169854PMC
June 2021

A commentary on "Preventive intramuscular phenylephrine in elective cesarean section under spinal anesthesia: A randomized controlled trial" [Int. J. Surg. 62 (2019) 5-11].

Int J Surg 2021 Jun 27;90:105977. Epub 2021 May 27.

Department of Gynaecology, Gansu Provincial Maternity and Child-care Hospital, Lanzhou City, 730050, Gansu, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijsu.2021.105977DOI Listing
June 2021

Corrigendum: E3 Ubiquitin Ligase UBR5 Promotes the Metastasis of Pancreatic Cancer Destabilizing F-Actin Capping Protein CAPZA1.

Front Oncol 2021 11;11:693855. Epub 2021 May 11.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

[This corrects the article DOI: 10.3389/fonc.2021.634167.].
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http://dx.doi.org/10.3389/fonc.2021.693855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147866PMC
May 2021

Efficacy of computerized cognitive training on improving cognitive functions of stroke patients: A systematic review and meta-analysis of randomized controlled trials.

Int J Nurs Pract 2021 May 25:e12966. Epub 2021 May 25.

Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.

Aim: To evaluate the effects of computerized cognitive training on the cognitive functions of stroke patients.

Background: With increased publications on computerized cognitive training, a meta-analysis is essential to determine the effects of computerized cognitive training among stroke patients.

Design: A systematic review and meta-analysis of randomized controlled studies.

Data Sources: Cochrane Library, Pubmed, EBSCO, Scopus, China National Knowledge Infrastructure, China Biology Medicine disc and Wanfang Database were explored to search for research studies from inception to January 2020.

Review Methods: Six outcomes indicators were considered to determine the effects of computerized cognitive training. Two reviewers were selected to search and independently appraise the available articles from various databases. Meta-analysis was performed using the RevMan 5.3 software.

Results: A total of 622 patients with 17 studies were included. Computerized cognitive training significantly improves global cognition, working memory, attention and executive function of stroke patients. However, there was inadequate evidence to demonstrate any effects of computerized cognitive training on activities of daily living and depression.

Conclusion: Computerized cognitive training improves the cognitive functions of stroke patients. However, further research studies are needed to confirm its efficacy in activities of daily living as well as on alleviating depression.
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http://dx.doi.org/10.1111/ijn.12966DOI Listing
May 2021

Cldn-7 deficiency promotes experimental colitis and associated carcinogenesis by regulating intestinal epithelial integrity.

Oncoimmunology 2021 May 11;10(1):1923910. Epub 2021 May 11.

Department of Oncology Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Intestinal epithelial barrier protects intestine from infection and injury, while chronic inflammation is a trigger for tumorigenesis. As a member of tight junctions (TJs) family, Claudin-7 (Cldn-7) is dedicated to maintaining cell polarity and TJs barrier integrity, and closely related to the development of inflammation and tumors. However, potential roles of Cldn-7 in intestinal inflammation and colitis-associated colorectal cancer (CAC) have not been well characterized in vivo. Here, we analyzed the expression profile of Cldn-7 in inflammatory bowel disease (IBD) and CAC. Colitis and colitis-cancer transformation models were established based on inducible intestinal conditional Cldn-7 gene knockout mice (Cldn7fl/fl;villin-CreERT2), by intraperitoneal injection of azomethane (AOM) and dextran sodium sulfate (DSS) feeding. Cldn-7 knockout promoted susceptibility to colitis and CAC, aggravated clinical symptoms, severely damaged intestinal epithelium, increased mucosal inflammation accompanied dysregulated cell proliferation-apoptosis. Epithelial barrier integrity was destroyed, and intercellular permeability was increased. After AOM/DSS induction, tumor burden and volume were increased, characterized by enhanced proliferation and activation of Wnt/β-catenin signaling pathway. Mechanistically, Cldn-7 deficiency promoted colitis and subsequently malignant transformation by destroying TJs integrity and increasing inflammatory cascade. Overall, based on Cldn-7 knockout mouse model, we have first demonstrated the key roles of Cldn-7 in maintaining intestinal homeostasis and preventing IBD and consequent CAC. AJs: adherens junctions; AOM: azomethane; Cldn-7: Claudin-7; CRC: colorectal cancer; CAC: colitis-associated colorectal cancer; CD: Crohn's disease; DSS: dextran sodium sulfate; DAI: disease activity index; EMT: epithelial-mesenchymal transition; FITC: fluorescence isothiocyanate; HB: hemoglobin; IBD: inflammatory bowel disease; IECs: intestinal epithelial cells; ISCs: intestinal stem cells; PLT: platelet; RBC: red blood cell; ROS: reactive oxygen species; TAM: tamoxifen; TJs: tight junctions; TCF/LEF: T-cell factor/lymphoid enhancer factor; UC: ulcerative colitis; WBC: white blood cell.
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http://dx.doi.org/10.1080/2162402X.2021.1923910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118418PMC
May 2021

Neurons and Astrocytes in Ventrolateral Periaqueductal Gray Contribute to Restraint Water Immersion Stress-induced Gastric Mucosal Damage via the ERK1/2 Signaling Pathway.

Int J Neuropsychopharmacol 2021 May 17. Epub 2021 May 17.

Key Laboratory of Animal Resistance Biology of Shandong Province, School of Life Science, Shandong Normal University, 88# Wenhua Road, Jinan 250014, China.

Background: The restraint water immersion stress (RWIS) model includes both psychological and physical stimulation, which may lead to gastrointestinal disorders and cause gastric mucosal damage. The ventrolateral periaqueductal gray (VLPAG) contributes to gastrointestinal function, but whether it is involved in RWIS-induced gastric mucosal damage has not yet been reported.

Methods: The expression of glial fibrillary acidic protein (GFAP), neuronal c-Fos and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) in the VLPAG after RWIS was assessed using western blotting and immunocytochemical staining methods. Lateral ventricle injection of astrocytic toxin L-a-aminoadipate (L-AA) and treatment with ERK1/2 signaling pathway inhibitor PD98059 were further used to study protein expression and distribution in the VLPAG after RWIS.

Results: The expression of c-Fos, GFAP, and p-ERK1/2 in the VLPAG significantly increased following RWIS and peaked at 1 h after RWIS. Lateral ventricle injection of the astrocytic toxin L-AA significantly alleviated gastric mucosal injury and decreased the activation of neurons and astrocytes. Treatment with the ERK1/2 signaling pathway inhibitor PD98059 obviously suppressed gastric mucosal damage as well as the RWIS-induced activation of neurons and astrocytes in the VLPAG.

Conclusions: These results suggested that activation of VLPAG neurons and astrocytes induced by RWIS through the ERK1/2 signaling pathway may play a critical role in RWIS-induced gastric mucosa damage.
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http://dx.doi.org/10.1093/ijnp/pyab028DOI Listing
May 2021

Functional Group-induced p-Doping of MoS by Titanium(IV) Bis(ammonium lactato) Dihydroxide Physisorption.

Chem Asian J 2021 Jul 28;16(13):1756-1761. Epub 2021 May 28.

Institute of Chemical Biology and Nanomedicine (ICBN), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, P. R. China.

P-type doping is of critical importance for the realization of certain high-performance electrical and optoelectronic devices based on molybdenum disulfide (MoS ). Charge transfer doping is a feasible strategy for tuning the conductance properties via facile treatment. In this work, the electrical properties of few-layer MoS were modulated with titanium(IV) bis(ammonium lactato) dihydroxide molecules (denoted as TALH) via physisorption. The functional groups such as electronegative hydroxyl (-OH) and carboxylate groups (-COO) included in TALH molecules are expected to induce p-doping effect through surface charge transfer when being attached to MoS . The p-doping is proved by X-ray photoelectron spectroscopy (XPS) with the downshift of Mo 3d and S 2p peaks. Control experiments and density functional theory calculations validate that the p-type doping mainly originated from the -OH group in TALH, which drew electrons from MoS . These results suggest that functional group-mediated p-doping effect show a path to modulate the carrier transition in MoS and enrich the molecule series for device modification.
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http://dx.doi.org/10.1002/asia.202100300DOI Listing
July 2021

Mulberry leaf activates brown adipose tissue and induces browning of inguinal white adipose tissue in type 2 diabetic rats through regulating AMPK signaling pathway.

Br J Nutr 2021 May 11:1-31. Epub 2021 May 11.

Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

The current epidemic of type 2 diabetes mellitus (T2DM) significantly affects human health worldwide. Activation of brown adipocytes and browning of white adipocytes are considered as a promising molecular target for T2DM treatment. Mulberry leaf, a traditional Chinese medicine, has been demonstrated to have multi-biological activities, including anti-diabetic and anti-inflammatory effects. Our experiment results showed that mulberry leaf significantly alleviated the disorder of glucose and lipid metabolism in T2DM rats including reducing body weight (BW) gain, Lee's index, food intake, inguinal white adipose tissue (IWAT) accumulation, blood lipid fasting insulin level and fasting blood glucose level, increasing the ratios of brown adipose tissue (BAT) mass to BW, and improving insulin sensitivity and liver function. In addition, mulberry leaf induced browning of IWAT by enhancing the expressions of brown-mark genes as well as beige-specific genes, including uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), PRD1-BF-1-RIZ1 homologous domain containing protein 16 (PRDM16), cell death inducing DFFA like effector A (Cidea), CD137 and transmembrane protein 26 (TMEM26). Mulberry leaf also activated BAT by increasing the expressions of brown-mark genes including UCP1, PGC-1α, PPARα, PRDM16 and Cidea. Moreover, mulberry leaf enhanced the expression of nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) genes that are responsible for mitochondrial biogenesis in IWAT and BAT. Importantly, mulberry leaf also increased the expression of UCP1 and carnitine palmitoyl transferase 1 (CPT1) protein in both IWAT and BAT via a mechanism involving Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and PGC-1α pathway. In conclusion, our findings identify the role of mulberry leaf in inducing adipose browning, indicating that mulberry leaf may be used as a candidate browning agent for the treatment of T2DM.
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http://dx.doi.org/10.1017/S0007114521001537DOI Listing
May 2021

Copy number signature analysis tool and its application in prostate cancer reveals distinct mutational processes and clinical outcomes.

PLoS Genet 2021 May 4;17(5):e1009557. Epub 2021 May 4.

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. This copy number signature analysis in PC provides distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.
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http://dx.doi.org/10.1371/journal.pgen.1009557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121287PMC
May 2021

The response mechanism of Hydrilla verticillata and leaf epiphytic biofilms to depth and nutrient removal.

Environ Sci Pollut Res Int 2021 Apr 30. Epub 2021 Apr 30.

Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, People's Republic of China.

The mechanism of morphological and physiological regulation of submerged aquatic plants (Hydrilla verticillata) is influenced by spatial and environmental changes related to water depth gradients. In the present study, changes in the aquatic microcosm were explored at the depth gradients of 0.3 m, 0.6 m, 0.9 m, 1.2 m, and 1.5 m, and the depth was recognized as a critical factor for improving water quality, especially for the removal of total phosphorus (TP) and recalcitrant protein-like molecules. At 0.9 m, the removal rates of TP and protein-like substances reached 78% and 18.67%, respectively, 1.76 times and 1.28 times the rates at 0.3 m. The maximum shoot/root growth and chlorophyll (a + b) suggest photosynthesis inhibition is minimal at 1.2 m. Fluctuations in enzyme activities imply an antioxidant response to lipid peroxidation damage under different oxidative stress. The adjusted activities of glutamine synthetase (GS) and alkaline phosphatase (APA) were an adaptive nutrient utilization strategy to different water depths. Microbiological diversity analysis of biofilms indicates that community structure changes in response to water depth. Considering the growth status and nutrient removal effects, the results indicate that the optimal planting depth for H. verticillata is 0.9-1.2 m. These findings contribute to understanding water purification mechanisms in depth gradients, and support the effective rebuilding and management of submerged macrophyte communities in natural shallow lakes.
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http://dx.doi.org/10.1007/s11356-021-14131-xDOI Listing
April 2021

Enantioselective Hydroesterificative Cyclization of 1,6-Enynes to Chiral γ-Lactams Bearing a Quaternary Carbon Stereocenter.

Org Lett 2021 05 28;23(9):3561-3566. Epub 2021 Apr 28.

Chang-Kung Chuang Institute, and Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China.

A palladium-catalyzed asymmetric hydroesterification-cyclization of 1,6-enynes with CO and alcohol was developed to efficiently prepare a variety of enantioenriched γ-lactams bearing a chiral quaternary carbon center and a carboxylic ester group. The approach featured good to high chemo-, region-, and enantioselectivities, high atom economy, and mild reaction conditions as well as broad substrate scope. The correlation between the multiple selectivities of such process and the -substitutes of the amide linker in the 1,6-enyne substrate has been depicted by the crystallographic evidence and control experiments.
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http://dx.doi.org/10.1021/acs.orglett.1c00952DOI Listing
May 2021

Quantifying the core driving force for the sustainable redevelopment of industrial heritage: implications for urban renewal.

Environ Sci Pollut Res Int 2021 Apr 26. Epub 2021 Apr 26.

School of Civil Engineering, Xi'an University of Architecture and Technology, 13 Yanta Rd, Beilin District, Xi'an, Shaanxi Province, China.

Industrial heritage redevelopment (IHR) is the redevelopment and utilization of original industrial buildings. The sustainable development of IHR projects is a major challenge that the construction industry must address to establish reasonable sustainable solutions for urban development. However, the relationship between the sustainable development of IHR and its potential driving forces has not yet been elucidated. In this paper, first, 25 sustainability drivers are identified through a comprehensive literature review. Second, key environmental, economic, social, and cultural sustainability attributes are determined through structured questionnaires and interviews. Through a confirmatory factor analysis, the core degree of the sustainability driving factors is quantified. On this basis, the important role of sustainability in urban renewal is discussed. The research shows that the core driving forces of the IHR projects are the (1) development status of the construction industry, (2) repair and maintenance costs, (3) soundness of laws and regulations, (4) suitability level of the development model, and (5) utilization of construction land. Besides, IHR projects have great potential, and improving the sustainability of their development is of great significance to urban renewal.
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http://dx.doi.org/10.1007/s11356-021-14054-7DOI Listing
April 2021

Neural mechanism for dynamic distractor processing during video target detection: Insights from time-varying networks in the cerebral cortex.

Brain Res 2021 Aug 24;1765:147502. Epub 2021 Apr 24.

The Henan Key Laboratory of Imaging and Intelligent Processing, PLA Strategy Support Force Information Engineering University, Zhengzhou 450001, China. Electronic address:

In dynamic video target detection tasks, distractors may suddenly appear due to the dynamicity of the visual scene and the uncertainty of the visual information, strongly influencing participants' attention and target detection performance. Moreover, the neural mechanism that accounts for dynamic distractor processing remains unknown, which makes it difficult to compensate for in EEG-based video target detection. Here, cortical activities with high spatiotemporal resolution were reconstructed using the source localization method. The time-varying networks among important brain regions in different cognitive phases, including information integration, decision-making, and execution, were identified to investigate the neural mechanism of dynamic distractor processing. The experimental results indicated that dynamic distractors could induce a P3-like component. In addition, there was obvious asymmetry between the two hemispheres during video target detection. Specifically, the brain responses induced by dynamic distractors were weak and more concentrated in the left hemisphere during the information integration phase; left superior frontal gyrus activity related to preparation for the presence of distractors was critical, while the attention network and primary visual network, especially in the left visual pathway, were more active for dynamic targets during the decision-making phase. These findings provide guidance for designing an effective EEG-based model for dynamic video target detection.
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http://dx.doi.org/10.1016/j.brainres.2021.147502DOI Listing
August 2021

Baicalin and Geniposide Inhibit Polarization and Inflammatory Injury of OGD/R-Treated Microglia by Suppressing the 5-LOX/LTB4 Pathway.

Neurochem Res 2021 Jul 23;46(7):1844-1858. Epub 2021 Apr 23.

Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine, Shaanxi Provincial Administration of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.

Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. Baicalin (BC), geniposide (GP), and their combination (BC/GP) have been shown to inhibit post-ischemic inflammatory injury by inhibiting the 5-LOX/CysLTs pathway. The aims of this study were to observe the inhibitory effects of BC/GP on the activation of microglial cells induced by oxygen glucose deprivation and reoxygenation (OGD/R) and to investigate whether the 5-LOX/LTB4 pathway was involved in these effects. Molecular docking showed that BC and GP exhibited considerable binding activity with LTB4 synthase LTA4H. BV-2 microglia were transfected with a 5-LOX overexpression lentiviral vector, and then OGD/R was performed. The effects of different concentrations of BC, GP, and BC/GP (6.25 μM, 12.5 μM, and 25 μM) on cell viability and apoptosis of microglia were evaluated by MTT and flow cytometry. The expression of TNF-α, IL-1β, NF-κB, and pNF-κB also was measured by ELISA, Western blots and immunofluorescence. Western blots and qRT-PCR analysis were used to determine the levels of CD11b, CD206, and 5-LOX pathway proteins. Results showed that BC, GP, and BC/GP reduced the apoptosis caused by OGD/R in a dose-dependent manner, and cell viability was significantly increased at a concentration of 12.5 μM. OGD/R significantly increased the release of TNF-α, IL-1β, NF-κB, pNF-κB, and CD11b. These effects were suppressed by BC, GP, and BC/GP, and the OGD/R-induced transfer of NF-κB p65 from the ctytoplasm to the nucleus was inhibited in microglia. Interestingly, the LTB4 inhibitor, U75302, exhibited the same effect. Also, BC, GP, and BC/GP significantly reduced the expression of 5-LOX pathway proteins. These results demonstrated that BC/GP inhibited OGD/R-induced polarization in BV2 microglia by regulating the 5-LOX/LTB4 signaling pathways and attenuating the inflammatory response. Our results supported the theoretical basis for additional in-depth study of the function of BC/GP and the value of determining its unique target, which might provide a new therapeutic strategy for ischemic cerebrovascular disease.
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http://dx.doi.org/10.1007/s11064-021-03305-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187209PMC
July 2021

The association of vitamin D and vitamin E levels at birth with bronchopulmonary dysplasia in preterm infants.

Pediatr Pulmonol 2021 Jul 20;56(7):2108-2113. Epub 2021 Apr 20.

Newborn Department, Shijiazhuang Fourth Hospital, Shijiazhuang, Hebei, China.

Background: Despite improvements made in neonatal care, bronchopulmonary dysplasia (BPD) is still the most common respiratory disease in preterm infants. The relationship between the blood contents of vitamin D/E in premature infants and BPD is still controversial.

Methods: Preterm infants were recruited as the research subjects. On the basis of the inclusion and exclusion criteria, a total of 133 eligible cases were finally included. A total of 63 preterm infants with a clear diagnosis of BPD and 5 preterm infants who died before the diagnosis of BPD were in the case group, and 65 non-BPD preterm infants with equivalent baseline characteristics were in the control group. The BPD group included 38 cases in Grade Ⅰ, 18 cases in Grade Ⅱ, and 12 cases in Grade Ⅲ. The contents of vitamin D and E in the cord blood of different groups were detected by high-performance liquid chromatography and enzyme-linked immunosorbent assay. Correlation analysis adopted the Pearson correlation analytic method.

Results: The serum vitamin D and E levels at birth were remarkably lower in the BPD group than the non-BPD group, both of which were also correlated with the severity of BPD. The vitamin D and E contents were negatively correlated with the oxygen support duration required for premature infants with BPD.

Conclusion: This study deepens our understanding of the field of BPD pathogenesis by demonstrating an association between vitamin D/E deficiency and BPD severity, suggesting that vitamin D and E might have potential clinical value in the prognosis and treatment of BPD.
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http://dx.doi.org/10.1002/ppul.25414DOI Listing
July 2021

Picophytoplankton identification by flow cytometry and high-throughput sequencing in a clean reservoir.

Ecotoxicol Environ Saf 2021 Apr 11;216:112216. Epub 2021 Apr 11.

China-UK Low Carbon College, Shanghai Jiao Tong University, 3 Yinlian Road, Shanghai 201306, China; School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Electronic address:

Understanding picophytoplankton variations that play important roles in the material circulation and energy flow are critical to assessing overall status of waterbody, especially for clean reservoirs which remain a relatively stable community structure and high species diversity due to lower nitrogen and phosphorus nutrients. However, their response to key environmental factors and tightly acting microbial remains poorly understood. Traditional quantification methods are limited, such as chlorophyll-a, turbidity and microscope. There are still many defects with present molecular analysis. In this study, a flow cytometric analysis and high-throughput sequencing combination methodology was developed and tested on clean water from a reservoir, by a monthly dynamic for a vegetative period April-September in 2019 to improve the accuracy of dynamic monitoring for the picophytoplankton system. More species of Pico-Cyanobacteria and Pico-Eukaryotes were discovered. The increased percentage of pigment compounds from 8.2% to 76.3% proves the effective reduce of heterotrophic disturbing and enrichment of target populations. Picophytoplankton that was previously neglected due to their low relative abundance has once again entered the scope of our eyes. Phytoplankton were divided into three categories. The first one was the highly abundant and frequently present taxa, the second one was the low-abundance but highly-transient population, and the third one was the low abundance and stable group. Synechococcus, Emiliania, Tetraselmis and Thalassiosira were dominant picophytoplankton and displayed obvious temporal and spatial distribution characteristics. Pico-PE rich Cyanobacteria and Nano-Eukaryotes with high transience abnormally increased in summer. Temperature, ammonia-N, nitrate-N, turbidity and total nitrogen were most influencing factors, while some picophytoplankton with special physiological structure showed distinct competitive advantages in the microbial community. As for the off-flavor compounds, the concentration of 2-methylisoborneol and geosmin were high even 66.7% and 20.8% of the samples exceeded their olfactory threshold. Chrysochromuina, Planktothrix and Microcystis might be the potential producers.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112216DOI Listing
April 2021

Molybdenum disulfide nanosheets vertically grown on self-supported titanium dioxide/nitrogen-doped carbon nanofiber film for effective hydrogen peroxide decomposition and "memory catalysis".

J Colloid Interface Sci 2021 Aug 27;596:384-395. Epub 2021 Mar 27.

Environmental Engineering and Science Program, Department of Chemical and Environmental Engineering (ChEE), University of Cincinnati, Cincinnati, OH 45221-0012, United States. Electronic address:

A self-supporting catalyst consisting of 1D/2D vertical molybdenum [email protected] dioxide/nitrogen-doped carbon nanofiber ([email protected]/NCNFs) was prepared and tested. It showed efficient hydrogen peroxide (HO) decomposition to generate hydroxyl radical (OH) and degradation of various pollutants under solar irradiation. The contribution of the increase in MoS edges for decomposing HO was 0.0698 min. That is 9.83 times the rate of the original MoS edges resulting from the vertical structure. Specially, the catalyst degraded various aromatic pollutants even in the dark by releasing electrons stored in its graphite component to realize "memory catalysis". Also, it exhibited high degradation efficiency under outdoor solar irradiation. The catalyst was easily separated from the treated water, avoiding complex separation processes. All these features suggest this catalyst has great potential in practical water and sewage treatment applications.
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http://dx.doi.org/10.1016/j.jcis.2021.03.140DOI Listing
August 2021

Pan-cancer noncoding genomic analysis identifies functional promoter mutation hotspots.

iScience 2021 Apr 9;24(4):102285. Epub 2021 Mar 9.

School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China.

Noncoding DNA sequences occupy more than 98% of the human genome; however, few cancer noncoding drivers have been identified compared with cancer coding drivers, probably because cancer noncoding drivers have a distinct mutation pattern due to the distinct function of noncoding DNA. Here we performed pan-cancer whole genome mutation analysis to screen for functional noncoding mutations that influence protein factor binding. Recurrent mutations were identified in the promoter of gene. These promoter hotspot mutations disrupt the binding of ELK4 transcription repressor, lead to the up-regulation of transcription. Physiologically ELK4 binds to the unmutated hotspot sites and is involved in DNA damage-induced transcriptional repression. Overall, our study not only identifies a detailed mechanism for gene deregulation in human cancers but also finds functional noncoding genetic alterations, with implications for the further development of function-based noncoding driver discovery pipelines.
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http://dx.doi.org/10.1016/j.isci.2021.102285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024666PMC
April 2021

Health-related quality of life in pediatric patients with partial onset seizures or primary generalized tonic-clonic seizures receiving adjunctive perampanel.

Epilepsy Behav 2021 05 8;118:107938. Epub 2021 Apr 8.

Eisai Inc., Woodcliff Lake, NJ, USA.

Rationale: Study 311 (E2007-G000-311; NCT02849626) was a Phase 3, multicenter, open-label single-arm study of adjunctive perampanel oral suspension in pediatric patients (aged 4 to <12 years) with partial-onset seizures (POS) (with/without secondarily generalized tonic-clonic seizures [SGTCS]) or primary generalized tonic-clonic seizures (PGTCS). Health-related quality of life (HRQoL) was an exploratory endpoint initially analyzed through simple descriptive summaries. The aim of this post hoc analysis was to provide a more thorough assessment of HRQoL.

Methods: This analysis focused on EQ-5D-Y data collected at Baseline, Week 23, and Week 52. Individual dimensions, visual analog scale (VAS) and summed misery index (MI) were evaluated at all visits and compared by seizure type (POS versus SGTCS versus PGTCS), age (4 to <7 versus 7 to <12), and use of concomitant enzyme-inducing antiepileptic drugs (EIAEDs) (yes versus no). Paretian Classification of Health Change (PCHC) analysis summarized the proportion of patients who showed improvement or deterioration in HRQoL. Waterfall plots assessed changes in EQ-5D-Y scores by treatment-emergent adverse events (TEAEs) and by reduction in seizure frequency. Health state utility values associated with differing seizure frequency states were estimated using a linear mixed model.

Results: One hundred and fifteen patients completed EQ-5D-Y at relevant study visits (Seizure type: POS n = 84 [of which 21 had SGTCS], PGTCS n = 31; Age: 4 to <7 years n = 30, 7 to <12 years n = 85; Concomitant EIAEDs: Yes n = 35, No n = 80). Completion rates out of those expected to complete EQ-5D-Y were high at both timepoints (84.4% at Week 23 and 97.2% at Week 52). Overall, VAS/MI remained stable over time (did not exceed minimal important difference); this was similar according to seizure type, age, and EIAED usage. In patients with 'no problems' on any EQ-5D-Y dimension at Baseline, nearly all retained their full health at Week 23 (94.7%), and all retained it at Week 52 (100.0%). PCHC analysis showed fewer patients with POS experienced deterioration in EQ-5D-Y than patients with PGTCS at Week 23 (24.1% versus 42.1%). Not experiencing a TEAE, or remaining seizure-free, was associated with improvements in VAS score at Week 23 compared to those experiencing TEAEs or seizures, respectively. Health state utility values (HSUVs) were estimated as follows: seizure free (LS Mean 0.914 [95% CIs 0.587, 1.240]), ≥1 seizure per year (0.620 [0.506, 0.734]), ≥1 seizure per month (0.596 [0.338, 0.855]), ≥1 seizure per week (0.284 [-0.014, 0.582]).

Conclusions: An in-depth analysis of EQ-5D-Y data allowed for a more nuanced exploration of HRQoL than previous descriptive summaries. Our findings provide evidence that perampanel as adjunctive therapy did not result in deterioration of patient HRQoL. The association between TEAEs or remaining seizure-free and HRQoL warrants further exploration. Increasing seizure frequency was associated with decreasing HSUVs; these can inform cost-effectiveness modeling of perampanel and other therapies aiming to reduce seizure frequency in pediatric patients.
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http://dx.doi.org/10.1016/j.yebeh.2021.107938DOI Listing
May 2021

ASIC1 and ASIC3 mediate cellular senescence of human nucleus pulposus mesenchymal stem cells during intervertebral disc degeneration.

Aging (Albany NY) 2021 04 6;13(7):10703-10723. Epub 2021 Apr 6.

Department of Orthopedics and Spine Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, Anhui, China.

Stem cell approaches have become an attractive therapeutic option for intervertebral disc degeneration (IVDD). Nucleus pulposus mesenchymal stem cells (NP-MSCs) participate in the regeneration and homeostasis of the intervertebral disc (IVD), but the molecular mechanisms governing these processes remain to be elucidated. Acid-sensing ion channels (ASICs) which act as key receptors for extracellular protons in central and peripheral neurons, have been implicated in IVDD where degeneration is associated with reduced microenvironmental pH. Here we show that ASIC1 and ASIC3, but not ASIC2 and ASIC4 are upregulated in human IVDs according to the degree of clinical degeneration. Subjecting IVD-derived NP-MSCs to pH 6.6 culture conditions to mimic pathological IVD changes resulted in decreased cell proliferation that was associated with cell cycle arrest and induction of senescence. Key molecular changes observed were increased expression of p53, p21, p27, p16 and Rb1. Instructively, premature senescence in NP-MSCs could be largely alleviated using ASIC inhibitors, suggesting both ASIC1 and ASIC3 act decisively upstream to activate senescence programming pathways including p53-p21/p27 and p16-Rb1 signaling. These results highlight the potential of ASIC inhibitors as a therapeutic approach for IVDD and broadly define an system that can be used to evaluate other IVDD therapies.
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http://dx.doi.org/10.18632/aging.202850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064223PMC
April 2021

Solvothermal synthesis of porphyrin-ferrocenyl conjugated microporous polymer nanospheres for shape-stable phase change materials with improved latent heat and cyclability.

J Colloid Interface Sci 2021 Aug 24;595:178-186. Epub 2021 Mar 24.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China. Electronic address:

Organic phase change materials (PCMs) have attracted considerable attention for thermal energy storage applications because of their non-toxicity, suitable working temperature range and excellent thermal/chemical stability. However, most traditional organic PCMs have small molecular structures and are prone to leakage during fusion. To address this problem and enhance the shape-stability of organic PCMs, nanosphere-shaped porphyrin-ferrocenyl conjugated microporous polymers (PFCMPs) with high porosity (~ 650 m/g) were solvothermally synthesized using a Diels-Alder reaction between 1,1'-ferrocenedicarboxaldehyde and pyrrole in the presence of glacial acetic acid and anhydrous Lewis acids (FeCl, AlCl, and CuCl). The PFCMPs were then encapsulated with PCMs, that is, 1-octadecanol (ODA), to prepare the composite materials of [email protected] The optimized composite exhibited a high latent heat (up to 153.8 J/g), excellent reversibility (negligible change in latent heat upon 100 cycles of heating-cooling), good shape stability, and long heat storage durability (425 s), making it a promising candidate for solar thermal energy engineering and management.
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http://dx.doi.org/10.1016/j.jcis.2021.03.111DOI Listing
August 2021

Case Report: Anti-NMDA Receptor Encephalitis With Bilateral Hearing Loss as the Initial Symptom.

Front Neurol 2021 17;12:648911. Epub 2021 Mar 17.

Jincheng People's Hospital Affiliated to Shanxi Medical University, Jincheng, China.

Anti--methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disease associated with the NMDA receptor. This paper describes a patient who presented with bilateral hearing loss as the initial symptom of anti-NMDAR encephalitis. We describe a 31-year-old young female with anti-NMDAR encephalitis who presented with bilateral severe hearing loss after brief loss of consciousness and then accompanied by other symptoms, such as generalized tonic-clonic seizures, manic episodes, excessive salivation, severe cognitive impairment, and complex non-convulsive status epilepticus. Great improvement was achieved by a combined treatment of steroid, IVIG, and plasmapheresis, especially after surgical removal of the ovarian teratoma. When she was discharged on hospital day 43, her hearing loss obtained a significant improvement. This case study and literature review investigated the impairment of hearing loss and its subsequent treatment in patients with anti-NMDAR encephalitis.
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http://dx.doi.org/10.3389/fneur.2021.648911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010237PMC
March 2021

LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice.

Genes (Basel) 2021 Mar 31;12(4). Epub 2021 Mar 31.

Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Capital Medical University, Center of Rare Diseases, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.

It has been shown that thoracic aortic aneurysm and dissection (TAAD) could be a Mendelian trait caused by a single gene mutation. The gene mutation leads to the development of human TAAD. The gene is a member of the lysyl oxidase gene family. We identified seven variants in the gene in 219 unrelated patients with TAAD by whole-exome sequencing (WES). To further investigate whether is a candidate causative gene for human TAAD, a knockout mouse was generated, and the mutant mice were treated by subcutaneous infusion of angiotensin II. We found that abrogation of did not induce a more severe thoracic or abdominal aortic aneurysm compared with the wild-type C57BL/6J mice. Our results suggest that may not play a major role in the development of angiotensin II-induced aortic aneurysm. The functional study using this animal model system is important for the evaluation of candidate genes of TAAD identified by WES.
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http://dx.doi.org/10.3390/genes12040513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066229PMC
March 2021

E3 Ubiquitin Ligase UBR5 Promotes the Metastasis of Pancreatic Cancer Destabilizing F-Actin Capping Protein CAPZA1.

Front Oncol 2021 12;11:634167. Epub 2021 Mar 12.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The ubiquitin-proteasome system (UPS) is a regulated mechanism of intracellular protein degradation and turnover, and its dysfunction is associated with various diseases including cancer. UBR5, an E3 ubiquitin ligase, is emerging as an important regulator of the UPS in cancers, but its role in pancreatic cancer is poorly understood. Here, we show that UBR5 is significantly upregulated in pancreatic cancer tissues. High UBR5 expression is correlated with increased lymph node metastasis and poor survival of patients. The loss-of-function and gain-of-function studies demonstrated that UBR5 substantially enhanced the migratory and invasive ability of pancreatic cancer cells. UBR5 knockdown also markedly inhibited cancer metastasis in the liver metastatic model of pancreatic cancer in nude mice, suggesting UBR5 as a potent metastatic promoter in pancreatic cancer. Furthermore, using co-immunoprecipitation combined with mass spectrometry analyses, CAPZA1, a member of F-actin capping protein α subunit family, was identified as a novel substrate of UBR5. UBR5 overexpression could promote the degradation of CAPZA1 via the UPS and induce the accumulation of F-actin, which has been described as an essential molecular event during the process of CAPZA1 deficiency-induced cancer cells migration and invasion. UBR5 knockdown significantly increased the intracellular level of CAPZA1 and CAPZA1 downregulation largely reversed the UBR5 knockdown-induced suppression of cell migration and invasion in pancreatic cancer cells. Collectively, our findings unveil UBR5 as a novel and critical regulator of pancreatic cancer metastasis and highlight the potential for UBR5-CAPZA1 axis as a therapeutic target for preventing metastasis in pancreatic cancer patients, especially in those with increased UBR5 expression.
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http://dx.doi.org/10.3389/fonc.2021.634167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994773PMC
March 2021