bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained Delivery of MMP-9 siRNA via Thermosensitive Hydrogel Accelerates Diabetic Wound Healing
Authors: Lan Biyun , Zhang Liming , Yang Liqun , Wu Junfeng , Li Na , Pan Chenglin , Wang Xiaoyi , Zeng Lexiang , Yan Li , Yang Chuan , Ren Meng
Published: February 2021

Excessive expression of matrix metalloproteinase 9 (MMP-9) impedes healing of diabetic chronic wounds, thus wound dressing that could effectively inhibit the expression of MMP-9 offers significant clinical translation for diabetic wound healing. Herein, a hybrid hydrogel dressing was developed for localized and sustained delivery of MMP-9 siRNA (siMMP-9). siMMP-9 was complexed with Gly-TETA (GT), the GT/siMMP9 complex was then loaded into a thermosensitive hydrogel based on Pluronic F-127 (PF) and methylcellulose (MC). In vitro, this hybrid hydrogel dressing exhibited negligible cytotoxicity, prolonged the release of GT/siMMP-9 for up to 7 days, and significantly reduced MMP-9 expression. In vivo assessment in diabetic rats demonstrated that hydrogel provided localized and sustained delivery via the thermosensitive controlled release of entrapped GT/siMMP-9 into wound tissues for 7 days, resulting in dramatic MMP-9 silencing which significantly improved diabetic wound closure. This hybrid hydrogel dressing exhibited excellent biocompatibility, with no observed systemic toxicity in rats. Taken together, the hybrid hydrogel dressing may constitute an effective and biocompatible means of enhancing diabetic wound healing through effective silencing of the MMP-9 gene, and this hydrogel delivery system also offers a platform for in vivo delivery of siRNA for the treatment of other diseases.
Unravelling the Anticancer Potential of a Square Planar Copper Complex: Toward Non-platinum Chemotherapy
Authors: Malik Manzoor Ahmad , Raza Md Kausar , Mohammed Arif , Wani Mohmmad Younus , Hashmi Athar Adil
Published: February 2021

Coordination compounds from simple transition metals are robust substitutes for platinumbased complexes due to their remarkable anticancer properties. In a quest to find new metal complexes that could substitute or augment the platinum based chemotherapy we synthesized three transition metal complexes C1-C3 with Cu(II), Ni(II), and Co(II) as the central metal ions, respectively, and evaluated them for their anticancer activity against human keratinocyte (HaCaT) cell line and human cervical cancer (HeLa) cell lines. These complexes showed different activity profiles with the square planar copper complex C1 being the most active with IC50 values lower than the widely used anticancer drug-cisplatin. Assessment of the morphological changes by DAPI staining and ROS generation by DCFH-DA assay exposed that the cell death occurred by caspase-3 mediated apoptosis. C1 displayed interesting interactions with Ct-DNA, evidenced by absorption spectroscopy and validated by docking studies. Together, our results suggest that binding of the ligand to the DNA-binding domain of p53 tumor suppressor (p53DBD) protein and the induction of apoptotic hallmark protein, caspase-3 upon treatment with the metal complex could be positively attributed to a higherlevel of ROS and the subsequent DNA damage (oxidation), generated by compound C1, that could well explain the interesting anticancer activity observed for this complex.
Relationships between social withdrawal and facial emotion recognition in neuropsychiatric disorders
Authors: Torre-Luque Alejandro , Viera-Campos Alba , Bilderbeck Amy C. , Carreras Maria Teresa , Vivancos Jose , Diaz-Caneja Covadonga M. , Aghajani Moji , Saris Ilja M. J. , Raslescu Andreea , Malik Asad , Clark Jenna , Penninx Brenda W. J. H. , Wee Nic Van der , Rossum Inge Winter-van , Sommer Bernd , Marston Hugh , Dawson Gerard R. , Kas Martien J. , Ayuso-Mateos Jose Luis , Arango Celso
Published: February 2021

This study aimed to investigate the role of social withdrawal in emotion recognition of patients with schizophrenia (SZ) or probable Alzheimer’s disease (AD). A sample of 156 participants was recruited: SZ patients (n = 53), AD patients (n = 46), and two age-matched control groups (SZc, n = 29; ADc, n = 28). All participants provided self-report measures of loneliness and social functioning, and completed a facial emotion detection task. As a result, neuropsychiatric patients (both groups) showed poorer performance in detecting both positive and negative emotions compared with their healthy counterparts (p < .01). Social withdrawal was associated with higher accuracy in negative emotion detection, across all groups. Additionally, neuropsychiatric patients with higher social withdrawal showed lower positive emotion misclassification. Our findings help detail the similarities and differences in social function and facial emotion recognition in two disorders rarely studied in parallel, AD and SZ. Transdiagnostic patterns in these results suggest that social withdrawal is associated with heightened sensitivity to negative emotion expressions, potentially reflecting hypervigilance to social threat. Across the neuropsychiatric groups specifically, this hypervigilance associated with social withdrawal extended to positive emotion expressions, an emotional-cognitive bias that may impact social functioning in people with severe mental illness.
The Systematic Analysis of lncRNA Expression in Ebola-infected Human Macrophages
Authors: Muthaiyan Mathavan , Naorem Leimarembi Devi , Sinnarasan VigneshwarSuriya Prakash , Paul Dahrii , Venkatesan Amouda
Published: February 2021

Ebola is a dangerous virus which causes severe headache, muscle pain, hemorrhagic fever, and multi-organ failure. The underlying mechanism of Ebola-human interaction at the molecular level remains unexplored. The recently reported research revealed that lncRNA are known to be important in the pathogenesis of viruses. The study carried out the comprehensive analysis of lncRNA identification in EBOLA, LPS and RESTV infected MDMs. In EBOLA, the total number of known lncRNA is EBOLA 555 in, in RESTV 476, in LPS 550 and the novel lncRNAs in EBOLA 142, RESTV 127, in LPS 136 identified. Also, differentially expressed lncRNAs and neighbourhood genes of each lncRNA about 100kb identified for analysis.The study reported the known and novel lncRNA in EBOLA, LPS and RESTV infected cells of MDMs. The results of the study may help to understand the immune response further.
New Normal Weather Breaks a Traditional Clothing Retail Calendar
Authors: Oh Jungmi , Ha Kyung-Ja , Jo Young-Heon
Published: February 2021

Background: Clothing businesses have complained of sluggish sales because of new normal weather, an increased variation of temperature and precipitation and the higher occurrence of extreme weather events. Traditionally, the business runs tied to calendar dates or retailing events, and the previous year's sales draw up a sales plan. This study questioned whether the sales planning method of the clothing business is valid and reliable for today. Results: Using weather observation data and Google Trends for the past 11 years, consumers' responses to weather changes were analyzed through the decision tree to learn about consumer insights. The month is the most significant predictor of seasonal clothing demand during a season, and consumers' responses to weather vary from month to month. Minimum temperature and maximum temperature were significant predictors in a particular month. Conclusions: Our results have important managerial implications. Rapid weather changes affect consumers’ demand. Clothing retailers can apply the predictive model to quickly respond to unexpected weather changes, prepare products with rapidly increasing demand not to miss sales opportunities, and adjust quantities and prices for products with sharp declines in demand.
FGF23, A Novel Muscle Biomarker Detected in The Early Stages of ALS
Authors: Si Ying , Kazamel Mohamed , Benatar Michael , Wuu Joanne , Kwon Yuri , Kwan Thaddaeus , Jiang Nan , Kentrup Dominik , Faul Christian , Alesce Lyndsy , King Peter H.
Published: February 2021

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease advancement offers a new direction for exploring the molecular basis or response to the underlying pathology of ALS.
Carboplatin-induced Senescence in Ovarian Cancer Cells Is Reversed Through EGFR and NF-κB Signaling
Authors: Li Yue , Fu Mingxu , Guo Ling , Sun Xiaoxiao , Chen Yuhang , Zhang Tianran , Qin Jinlong , Shao Xiaowen
Published: February 2021

Background: Metastases and recurrence of ovarian cancer after surgery and chemotherapy account for most cancer-related deaths, yet the mechanism underlying metastases and recurrence remains poorly understood. Recent evidence demonstrates that although long-lasting cells were considered tumor suppressors, senescent cancer cells, can induce the metastases and recurrence. In this study, we focused on the fate of ovarian cancer cells treated with carboplatin and explored the mechanism underlying ovarian cancer cell recovery from chemotherapy-induced senescence. Methods: SÁ-β-galactosidase staining was used to detect the impact of carboplatin on senescence of ovarian cancer cells. Cell proliferation was determined using direct cell counting, clone formation assay and 3D tumor spheroid formation assay. Lentivirus-mediated transduction was used to silence or upregulate EGFR expression. Quantitative real-time PCR and western blot analysis validated the efficacy of the knockdown or overexpression effect. Immunofluorescence staining and western blot analysis were used to examined the expression of EGFR and NF-KB. Cell death was determined using trypan blue staining assay. Results: Ovarian cancer cells treated by carboplatin exhibit a senescence-like phenotype indicated by SA-β-galactosidase positive staining. Importantly, carboplatin-induced senescence-like phenotype is reversible. In ovarian cancer cells, EGFR positively regulated cells proliferation, decreased carboplatin-induced senescence and upregulated the NF-κB1 protein level. EGFR/NF-κB1 upregulation promoted the recovery of ovarian cancer cells from senescence and chemoresistance to carboplatin. Conclusions: Ovarian cancer cells treated with carboplatin displayed a reversible senescence-like phenotype that could be combined with EGFR or NF-κB1 inhibitors to improve treatment effects.
High or Low Temperature Extraction, Which Is More Conducive to Triphala Aginst Chronic Pharyngitis?
Authors: Ran fei , Han xue , Deng xuan , Wu Zhenfeng , Huang Hanzhou , Qiu Min , Song Jao , Wei Xichuan , Zhang Dingkun , Wang Yu , Fan Sanhu , Lin Junzhi , Han Li
Published: February 2021

BackgroundTriphala is a world famous herbal formula, its therapeutic effect on chronic pharyngitis has been confirmed in the majority of patients in China. However, the effects of current industrial extraction methods on its anti chronic pharyngitis components and activities are still unclear Methods:The network pharmacology was used to analyze the material basis, targets and pathways of Triphala for chronic pharyngitis. HPLC were used to compare the fingerprint profile and content of components between the two extracts. The antioxidant and anti chronic pharyngitis activities of the two extracts were compared by DPPH assay and ammonia induced chronic pharyngitis model in rats. Results:The network pharmacology results showed that the active ingredients of Triphala for chronic pharyngitis are epigallocat echin 3 gallate catechin , epicatechin , epicatechin gallate , g allocatechin , quercetin luteolin leucodelphinidin and other flavonoids, phenolic acids such as gallic acid and ellagic acid, alkaloids such as ellipticine , cheilanthifoline, and hydrolyzed tannins such as corilagin and chebulic acid . The high temperature reflux extract and the low temperature decompressing inner ebullition extract have extremely significant differences in the fingerprint profile. Among them, the content of 8 active ingredients of gallic acid, ellagic acid, chebulic acid , catechin, epicatechin, corilagin, quercetin, and epicatechin gallate in the reflux extract is 1.1 to 5.3 times as much as decompressing inner ebullition extract. The free radical scavenging ability of reflux extract is significantly stronger than that of decompression extract (p<0.01), and it has a repairing effect on pharyngeal mucosal damage (reducing keratinization or hyperplasia of mucosal epithelium, reducing inflammatory cell infiltration and bleeding), and reducing IL 1β (P 0.05), IL 6 (p 0.05), TNF α overexpression ability is stronger than the decompressing inner ebullition extract. Conclusions:gallic acid, ellagic acid, chebulic acid , catechin, epicatechin, corilagin and epicatechin gallate are the basic aglycones or oligomers of tannin. and high temperature reflux extraction can significantly promote temperature reflux extraction can significantly promote tthe occurrence of the he occurrence of the hydrolysis of tannins significantly increases the content of hydrolysis of tannins significantly increases the content of these components, and the these components, and the antianti--chronic pharyngitis activity is enhanced. chronic pharyngitis activity is enhanced. It is suggested that high temperature It is suggested that high temperature reflux extraction should be used in the treatment of chronic phreflux extraction should be used in the treatment of chronic pharyngitis.aryngitis.
Ropivacaine Induce G0 / G1 Phase Cell Cycle Arrest and Apoptosis of PC12 Cells Via Inhibiting Mitochondrial STAT3 Translocation
Authors: Zeng Lian , Zhang Zhen , Zhang Fuyu , Liu Chenguang , He Jiafeng , Chen Huaxian , Wang Qingsong , Ding Xudong , Luo Huiyu
Published: February 2021

Signal transducer and activator of transcription 3 (STAT3) has been shown to have neuroprotective effects via the non-canonical activation and mitochondrial translocation, but its effect on ropivacaine induced neurotoxicity is unclear. Our previous studies have revealed that apoptosis was an important mechanism of ropivacaine induced neurotoxicity, so this study is to explore the relationship between STAT3 with ropivacaine induced apoptosis. Our results showed that ropivacaine decreased PC12 cell viability, arrested the cells in the G0 / G1 phase, induced cell apoptosis and oxidative stress, and damaged mitochondrial functions. In addition, the serine727 (Ser727) phosphate activation of STAT3 was inhibited by ropivacaine. Ropivacaine decreased the p-STAT3 (Ser727) expression in the mitochondria, and increased p-STAT3 (Ser727) expression in the cytoplasm, so that it inhibited mitochondrial STAT3 translocation. To explore the potential connection between STAT3 with ropivacaine, the autodock-vina was used to examine the interaction between STAT3 and ropivacaine, and results showed that ropivacaine could bind to STAT3. Furthermore, the apoptosis of the spinal cord was increased and the p-STAT3 (Ser727) expression in the spinal cord was reduced after ropivacaine treatment. our findings illustrated that ropivacaine induced neurotoxicity by increasing the apoptotic levels, the activation and mitochondrial translocation of STAT3 were inhibited by ropivacaine. There may be an internal connection between these phenomena.
Significant Benefit of Everolimus In a Patient With Urothelial Bladder Cancer Harboring A Rare M1043I Mutation of PIK3CA
Authors: Pan Shouhua , Li Si , Xiao Mingzhe , Chen Dongsheng , Li Junlong
Published: February 2021

Urothelial bladder cancer (UBC) is a common malignancy with significant mortality worldwide. However, treatment options of UBC were mainly chemotherapy and immunotherapy since few targeted agents had shown efficacy in UBC. In recent studies, everolimus has showed antitumor activity in patients harboring aberrations in PI3K/Akt/mTOR pathway in multiple tumor types. Here we report a patient with metastatic UBC harboring a rare M1043I mutation of PIK3CA detected by DNA based next-generation sequencing. The patient received everolimus as first-line therapy after palliative transurethral resection. Within one months, the residual lymph node metastases achieved complete response and no more ostealgia was reported. To our knowledge, this is the first case reporting a significant benefit from everolimus in PIK3CA mutant UBC, suggesting the rare M1043I mutation variant may be a potential biomarker of sensitivity to everolimus. Further mechanism insights and clinical studies are needed to clarify the effectiveness of everolimus in patients with PIK3CA M1043I mutation.
An Original Aspirin-Containing Carbonic Anhydrase 9 Inhibitor Overcomes Hypoxia-induced Drug Resistance to Enhance The Efficacy of Myocardial Protection
Authors: Zhou Wen , Zhang Bin , Fan Keyu , Yin Xiaojian , Liu Jinfeng , Gou Shaohua
Published: February 2021

Purpose Hypoxic microenvironment plays a vital role in myocardial ischemia injury, generally leading to the resistance of chemotherapeutic drugs. This induces an intriguing study on mechanism exploration and prodrug design to overcome the hypoxia induced drug resistance.Methods In this study, we hypothesized that the overexpression of carbonic anhydrase 9 (CAIX) in myocardial cells is closely related to the drug resistance. Herein, bioinformatics analysis, gene knockdown and overexpression assay certificated the correlation between CAIX overexpression and hypoxia. An original aspirin-containing CAIX inhibitor AcAs has been developed.Results Based on the downregulation of CAIX level, both in vitro and in vivo, AcAs can overcome the acquired resistance, and more effectively attenuate myocardial ischemia and hypoxia injury than that of aspirin. CAIX inhibitor is believed to recover the extracellular pH value so as to ensure the stable effect of aspirin.Conclusion Results indicate great potential of CAIX inhibitor for further application in myocardial hypoxia injury therapy.
The Impact of Ossification Spread on Cervical Spine Function in Patients With Ossification of The Posterior Longitudinal Ligament
Authors: Katsumi Keiichi , Hirai Takashi , Yoshii Toshitaka , Maki Satoshi , Mori Kanji , Nagoshi Narihito , Nishimura Soraya , Takeuchi Kazuhiro , Ushio Shuta , Furuya Takeo , Watanabe Kei , Nishida Norihiro , Watanabe Kota , Kaito Takashi , Kato Satoshi , Nagashima Katsuya , Koda Masao , Ito Kenyu , Imagama Shiro , Matsuoka Yuji , Wada Kanichiro , Kimura Atsushi , Ohba Tetsuro , Katoh Hiroyuki , Matsuyama Yukihiro , Ozawa Hiroshi , Haro Hirotaka , Takeshita Katsushi , Watanabe Masahiko , Matsumoto Morio , Nakamura Masaya , Yamazaki Masashi , Okawa Atsushi , Kawaguchi Yoshiharu
Published: February 2021

Ossification of the posterior longitudinal ligament (OPLL) is a progressive disease. The bridging of ossified lesions to the vertebral body gradually increases, thereby decreasing the mobility of the cervical spine; thus, cervical spine function may decrease over time. However, cervical spine function in patients with cervical OPLL has not been evaluated in large prospective studies. Therefore, we conducted a prospective multicenter study to clarify whether ossification spread can influence cervical spine function and quality of life (QOL) in patients with cervical OPLL. In total, 238 patients (162 men, 76 women; mean age, 63.9 years) were enrolled from 16 institutions. Each patient underwent whole spine computed tomography and was evaluated cervical spine function and QOL using the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). In the multivariate regression analysis, a higher neck VAS score and a larger number of bridge formations of OPLL in the whole spine were significant predictors of adverse outcomes related to cervical spine function. This is the first prospective multicenter study to reveal the impact of ossification spread on cervical spine function. These findings are important to understand the natural course of OPLL and can serve as controls when evaluating postoperative cervical spine function.
Faradarmani Consciousness Field Suppresses Alzheimer’s Disease Development in Both in Vitro and in Vivo Models of The Disease
Authors: Taheri Mohammad Ali , Torabi Sara , Nabavi Noushin , Semsarha Farid
Published: February 2021

Background: Alzheimer’s Disease (AD) is one of the most common causes of dementia, imposing large financial and psychological burdens on nations worldwide. Thus, we are in dire need for new treatment strategies or drugs for this disease. The aim of this study is to investigate the effects of a novel non-pharmacological method in the treatment of Alzheimer’s disease, based on Taheri's Consciousness Field approach. This approach works at the level of cellular and molecular processes and is tested in neuronal cells of AD mouse models. Methods: In this study, we established a neuron cell culture from an AD mouse model as well as a traumatic brain injury mouse model. We then measured changes in amyloidopathy, tau protein content, microtubule assembly, neuronal cell survival, and finally behavior of TBI mice in elevated Plus Maze under treatment of the Faradarmani Consciousness Field (FCF). Results: According to the results of this study, treatment of neural cell and mouse model of Alzheimer's disease by the FCF, leads to about complete survival of neural cell models and elimination of amyloidopathy and tau protein and remarkable behavioral improvement of the treated TBI mice model in the elevated plus maze. Conclusions: Based on the results, the FCF treatment suppresses AD development in the laboratory models. In this regard, conducting a human clinical study with the aim of introducing a new global complementary and alternative medicine in AD treatment is highly recommended.
NEDD4 Regulates Ubiquitination and Stability of the Cell Adhesion Molecule IGPR-1 Via Lysosomal Pathway
Authors: Sun Linzi , Amraei Razie , Rahimi Nader
Published: February 2021

The cell adhesion molecule immunoglobulin and proline-rich receptor-1 (IGPR-1) regulates various critical cellular processes including, cell-cell adhesion, mechanosensing and autophagy. However, the molecular mechanisms governing IGPR-1 cell surface expression levels remains unknown. In the present study, we used an in vitro ubiquitination assay and identified ubiquitin E3 ligase NEDD4 and the ubiquitin conjugating enzyme UbcH6 involved in the ubiquitination of IGPR-1. In vitro GST-pulldown and in vivo co-immunoprecipitation assays demonstrated that NEDD4 binds to IGPR-1. Over-expression of wild-type NEDD4 downregulated IGPR-1 and deletion of WW domains (1-4) of NEDD4 revoked its effects on IGPR-1. Similarly, knockdown of NEDD4 increased IGPR-1 levels in A375 melanoma cells. Likewise, deletion of 57 amino acids encompassing polyproline rich (PPR) motifs on the C-terminus of IGPR-1 nullified the binding of NEDD4 with IGPR-1. Furthermore, we demonstrate that NEDD4 promotes K48- and K63-dependent polyubiquitination of IGPR-1. The NEDD4-mediated polyubiquitination of IGPR-1 stimulated lysosomal-dependent degradation of IGPR-1 as the treatment of cells with the lysosomal inhibitors, bafilomycine and ammonium chloride increased IGPR-1 levels in the HEK-293 cells ectopically expressing IGPR-1 and in multiple human skin melanoma cell lines. Hence, these findings suggest that ubiquitin E3 ligase NEDD4 is a key regulator of IGPR-1 with a significant implication in the therapeutic targeting of IGPR-1.
Identification of Potential Metabolic Biomarkers in Predicting Esophageal Varices Needing Treatment in Patients With Liver Cirrhosis
Authors: Moon Chung-Man , Shin Sang Soo
Published: February 2021

Background: The goal of this study was to determine the diagnostic performance of in vivo quantitative proton magnetic resonance spectroscopy (1H-MRS) to identify the presence of esophageal varices needing treatment (VNT), as well as to investigate its correlation with clinical variables in patients with liver cirrhosis. Methods: Forty cirrhotic patients without VNT showing negative red color sign, and 40 cirrhotic patients with VNT showing positive red color sign underwent laboratory tests, esophago-gastro-duodenoscopy, and 1H-MRS with single-voxel localization in cirrhotic liver parenchyma. Results: The levels of lactate+triglyceride (TG) and choline in cirrhotic patients with VNT were significantly higher than those of cirrhotic patients without VNT. Lactate+TG and choline levels were positively correlated with spleen diameter and negatively correlated with platelet count in the combined group of cirrhotic patients with and without VNT. In cirrhotic patients with VNT, older age, longer spleen diameter, lower platelet counts, and lower ratios of platelet count/spleen diameter were independently associated with an increase of lactate+TG and choline metabolites in the presence of esophageal VNT. Additionally, the area under the curve used to distinguish cirrhotic liver with VNT from cirrhotic liver without VNT was 1.00 (95% confidence interval [CI]: 0.95–1.00) for lactate+TG and 0.67 (95% CI 0.55–0.77) for choline. Conclusions: Our study demonstrated that higher hepatic lactate+TG and choline levels in cirrhotic patients in conjunction with longer spleen diameter, lower platelet counts, and lower ratios of platelet count to spleen diameter were associated with the presence of esophageal VNT and the risk of developing variceal bleeding. Therefore, in vivo, 1H-MRS may be an effective tool for diagnosing and predicting esophageal VNT in patients with liver cirrhosis.
Evidence Review, Co-Production and Prototyping A Process of Creating a Consumer Research Contact List in a Paediatric Health Setting: The PARTICIPATE Project
Authors: Gill Fenella Jane , Pienaar Catherine , Jones Tanya
Published: February 2021

The impact of child health research can be far reaching; affecting children’s immediate health, their adult health, the health of future generations and the economic wellbeing of countries. Consumer and community involvement is increasingly recognised as key to successful research recruitment. Systematic approaches to research recruitment include research registries or research contact lists. Objective: Develop a process of creating a consumer research contact list for participating in future research opportunities at a children’s health service.Methods: A healthcare improvement approach used a 3 stage framework; 1) evidence review and consultation 2) co-production of a research communications plan with stakeholders and consumers, including a draft research information brochure 3) prototyping involved iteratively testing the brochure, surveying parents or carers who attended outpatient clinics or the hospital Emergency Department, and conducting follow up telephone calls.Results: There was overall support for the creation of a research contact list, but some unknowns remain. 367 parents or carers completed the survey and 36 participated in a follow up telephone call. Over half were willing to join a research contact list and more than 90% of the children of parents or carers surveyed were not currently participating in research. Several potential barriers identified by stakeholders were dispelled. Research communications and a future contact list should be available in electronic form.Conclusions: There was strong support for creating a research contact list. The co‑production approach will inform our future directions including creation of an electronic research contact list easily accessible by consumers of the children’s health service
Porous Design of SiCNWs/SiC Nanocomposites with High Strength and Low Thermal Conductivity
Authors: Ruan Jing , Yang Jinshan , Yan Jingyi , You Xiao , Wang Mengmeng , Hu Jianbao , Zhang Xiangyu , Ding Yusheng , Dong Shaoming
Published: February 2021

Porous SiC composites with lightweight, high strength and low thermal conductivity design can be obtained by constructing porous silicon carbide nanowires (SiCNWs) network and controlling chemical vapor infiltration (CVI) process. The SiCNWs network with an optimized volume fraction (13.6%) and uniform structure is prepared by mixing SiCNWs and polyvinyl alcohol (PVA) firstly. SiCNWs reinforced porous SiC composite (SiCNWs/SiC) with a small uniform pore can be obtained by controlling the chemical deposition kinetics. The morphology of the grown SiC matrix, from the spherical particles to the hexagonal pyramid particles, can be influenced by the deposition parameters like temperature and reactive gas concentration. The strength of the lightweight SiCNWs/SiC composites reach 47.8 MPa with a porosity of 64% and thermal conductivity of 1.2 W/(m∙K), which shows the toughening effect and insulation design with low thermal conductivity.
Spatio-temporal Variations in the Physiological Profiles of Streambed Bacterial Communities: Implication of Wastewater Treatment Plant Effluents
Authors: Akinwole Philips O , Guta Amerti , Draper Madeline , Atkinson Sophia
Published: February 2021

The effluents of wastewater treatment plants (WWTPs) represent a complex mixture of nutrients and toxic substances, thus, the potential exists for the effluents to significantly impact the biochemical characteristics and bacterial communities of the receiving water. We examined spatial and seasonal patterns, and the impact of effluents on microbial biomass, bacterial community structure, and metabolic diversity on a fourth-order stream. We took triplicate sediment samples at five different locations along a 5,000m transect over three sampling periods. We quantified bacterial community structure as community-level physiological profiles and biomass with phospholipid phosphate analysis. Our findings highlight the worrisome impacts of effluents on microbial biomass and bacterial metabolic diversity on the receiving water. Microbial biomass was significantly higher at the WWTP outfall compared to upstream and downstream sites and correlated positively with sediment physicochemical parameters. Furthermore, our data revealed significant spatial differences in bacterial community structure in the context of WWTP impact. High nutrient availability (lower carbon/nitrogen ratios) at the outfall increased site-specific bacterial metabolic diversity in winter but decreased the same in fall. Seasonal changes in the sedimentary microbial biomass and bacterial carbon substrate utilization were evident regardless of the spatial variations or impacts of the wastewater effluents. Communities in fall showed more versatile substrate utilization patterns than the winter communities. These results suggest that WWTP effluents significantly increased microbial biomass and highlight its mixed effects on bacterial community structure and metabolic diversity. Also, our data underscore a close association between sedimentary physicochemical parameters and the associated microbial functional activities.
Potential therapeutic targeting of lncRNAs in cholesterol homeostasis
Authors: Ye Wenchu , Huang Shi-Feng , Hou Lian-Jie , Long Hai-Jiao , Jiang Ting , Yin Kai , Hu Ching Yuan , Zhao Guo-Jun
Published: February 2021

Maintaining cholesterol homeostasis is essential for normal cellular and systemic functions. Long non-coding RNAs (lncRNAs) represent a mechanism to fine-tune numerous biological processes by controlling gene expression. LncRNAs have emerged as important regulators in cholesterol homeostasis. Dysregulation of lncRNAs expression is associated with lipid-related diseases, suggesting that manipulating the lncRNAs expression could be a promising therapeutic approach to ameliorate liver disease progression and cardiovascular disease (CVD). However, given the high-abundant lncRNAs and the poor genetic conservation between species, much work is required to elucidate the specific role of lncRNAs in regulating cholesterol homeostasis. In this review, we highlighted the latest advances in the pivotal role and mechanism of lncRNAs in regulating cholesterol homeostasis. These findings provide novel insights into the underlying mechanisms of lncRNAs in lipid-related diseases and may offer potential therapeutic targets for treating lipid-related diseases.
Plasmonic Hot Electron Induced Layer Dependent Anomalous Fröhlich Interaction in InSe
Authors: Rahaman Mahfujur , Aslam Muhammad , He Lu , Madeira Teresa , Zahn Dietrich
Published: February 2021

InSe is one of the most promising two-dimensional (2D) materials for electronic and optoelectronic applications because of its favourable bandgap and superior electron mobility compared to other layered semiconductors. However, due to the polar nature of InSe, Fröhlich interaction plays an important role in electrical transport, which becomes more significant in reduced dimensionality. Until now, it is not yet known how the dimensionality influences the strength and nature of the Fröhlich polaronic effect in InSe. Here, we report on layer dependent anomalous Fröhlich interaction in InSe from bulk to monolayer with the aid of plasmonic hot electron doping. When excited near the localized surface plasmon resonance, plasmonic nanostructures produce highly energetic electrons (known as hot electrons), which can be captured by a semiconductor such as InSe at the interface. These electrons then couple to the polar optical phonons via the Fröhlich interaction in InSe. With the aid of the strong plasmonic field, the Fröhlich interaction enabling us to monitor the polar phonons in conventional Raman measurements. We prepared nanostructures with three different metals (Ag, Au, and Al) using nanosphere lithography on InSe to study the hot electron doping effect by means of Raman spectroscopy. A finite element method simulation was used to understand the coupling between the plasmonic nanostructures and InSe. We observed that the intensity of polar LO phonon modes initially increases gradually with decreasing layer number and then drops drastically from 7L to 6L, i.e. at the thickness where the transition from quasi-direct to indirect bandgap occurs at room temperature. Additionally, a gradual decrease of intensity of the polar modes with decreasing layer thickness below this transition point is observed, which is due to the increasing indirect bandgap nature of InSe suggesting reduced Fröhlich coupling. Our results shed light on fundamental understanding of Fröhlich interaction in InSe, which is crucial for electronic and optoelectronic applications of this promising 2D material.
Long-read Time-course Profiling of the Host Cell Response to Herpesvirus Infection Using Nanopore and Synthetic Long-Read Transcriptome Sequencing 
Authors: Maróti Zoltán , Moldován Norbert , Torma Gábor , Jefferson Victoria A. , Csabai Zsolt , Gulyás Gábor , Dörmő Ákos , Boldogkői Miklós , Kalmár Tibor , Meyer Florencia , Tombácz Dóra , Boldogkői Zsolt
Published: February 2021

Third-generation sequencing is able to read full-length transcripts and thus to efficiently identify RNA molecules and transcript isoforms, including transcript length and splice isoforms. In this study, we report the time-course profiling of the effect of bovine alphaherpesvirus type 1 on the gene expression of bovine epithelial cells using direct cDNA sequencing carried out on MinION device of Oxford Nanopore Technologies. These investigations revealed a substantial up- and down-regulatory effect of the virus on several gene networks of the host cells, including those that are associated with antiviral response, as well as with viral transcription and translation. Additionally, we report a large number of novel bovine transcripts identified by nanopore and synthetic long-read sequencing. This study demonstrates that viral infection does not lead to a change in the average distance between promoters and transcription start sites, and between polyadenylation signals and transcription end sites. However, it causes differential expression of transcript isoforms. We could not detect an increased rate of transcriptional readthroughs as described in another alphaherpesvirus. According to our knowledge, this is the first report on the use of LoopSeq for the analysis of eukaryotic transcriptomes. This is also the first report on the application of nanopore sequencing for the kinetic characterization of cellular transcriptomes. This study also demonstrates the utility of nanopore sequencing for the characterization of dynamic changes of transcriptomes in any organisms.
Liver kinase B1 rs9282860 polymorphism and risk for multiple sclerosis in White and Black Americans
Authors: Boullerne Anne I , Wallin Mitchell T , Culpepper William J , Maloni Heidi , Boots Elizabeth A. , Sweeney Dagmar M , Feinstein Douglas L
Published: February 2021

We previously reported that a single nucleotide polymorphism (SNP) rs9282860 in serine threoninekinase 11 (STK11) gene which codes for liver kinase B1 (LKB1) has higher prevalence in Whiterelapsing-remitting multiple sclerosis (RRMS) patients than controls. To determine if this SNP is a riskfactor for MS in other populations, we assessed its prevalence in samples collected from AfricanAmerican (AA) persons with MS (PwMS) and controls at multiple Veterans Affairs (VA) Medical Centersand from a network of academic MS centers. There were no significant differences in average age atfirst symptom onset, diagnosis, disease duration, or disease severity between RRMS patients recruitedfrom VAMCs versus non-VAMCs. The SNP was more prevalent in AA than White PwMS, however onlyin secondary progressive MS (SPMS) patients was that difference statistically significant. AA SPMSpatients had higher STK11 SNP prevalence than non-MS controls; and in that cohort the SNP wasassociated with older age at symptom onset and at diagnosis. The results suggest that the STK11 SNPrepresents a risk factor for SPMS in AA patients, and is associated with an older age of symptom onsetand diagnosis.
Equol effects on AGE skin products, visceral fat, and climacteric symptoms in post-menopausal women
Authors: Yoshikata Remi , Myint Khin Zay Yar , Ohta Hiroaki , Ishigaki Yoko
Published: February 2021

Objective: We investigated the effect of an equol-containing supplement on metabolism and aging, and climacteric symptoms, with respect to internally-produced equol. Methods: A single center, randomized controlled trial (registration number: UMIN000030975) on 57 post-menopausal Japanese women (mean age: 56±5.37 years), was conducted. Twenty-seven women received the equol supplement, while the remaining received placebo. Metabolic and aging-related biomarkers were compared before and after the 3-month intervention. Climacteric symptoms were assessed every month using a validated self-administered questionnaire in Japanese post-menopausal women. Results: Three months post intervention, the treatment group showed significant improvement in climacteric symptoms, when compared to the placebo group (81% vs. 53% respectively, p=0.045). We did not observe any beneficial effect on metabolic and aging-related biomarkers in the intervention group. However, in certain populations significant improvement in skin auto-fluorescence, which is a measurement of AGE skin products, and visceral fat area was observed, especially among equol producers. Conclusion: Women receiving equol supplement showed improved climacteric symptoms. This study offered a new hypothesis that there may be a synergy between supplemented equol and endogenously-produced equol to improve skin aging and visceral fat in certain populations.
Perception of Jordanian Pharmacy Students towards Community Pharmacy-Virtual Training Experience during COVID-19 Outbreak
Authors: Barakat Muna , Al-Qudah Rajaa A. , Farha Rana Abu , ALSalamat Husam A. , Akour Amal
Published: February 2021

Background: Nowadays, it is clear for the whole world that the coronavirus disease (COVID-19) pandemic had substantial consequences on various sectors including social, economic and education. Pharmacy education includes community pharmacy practice training, and in many schools, it has been shifted to virtual modality utilizing distance learning. This study aims to assess the perception of pharmacy students towards community pharmacy practice virtual training during the COVID-19 period. Methods: Senior pharmacy students were included in this study. Accredited and certified community pharmacy preceptors were asked to simulate the community pharmacy training and record that as videos, which were evaluated and assessed by expert academics before being delivered to students. A validated online questionnaire was then distributed for the students for self-administration through Microsoft teams to evaluate their perception. Results: A convenience sample (n=109) of senior pharmacy students were recruited. The majority of the participants were females (70.6%) and the median age of students was 22.0 years (IQR= 1). Around half of the participants showed positive perceptions towards the virtual training module and the pharmacy training preceptors. A 46.8% of the students benefited from the virtual training in time management and 43.1% in developing lifelong learning skills. The absence of eye contact during the learning was the most important barrier revealed by the students (52.3%). Half of the students agreed/strongly agreed that combining the virtual and conventional techniques for future training would improve training outcomesConclusion: This is the first study assessing perception towards virtual training in Jordan, which was positive among pharmacy students. Such results could spot the light on the value of hybrid education and training (virtual with actual) in the pharmacy field. However, there is a crucial need for well-designed studied modules to comply with the intended learning outcomes.
Spread of SARS-CoV-2 Genomes on Genomic Index Maps of Hierarchy - Compared with B.1.1.7 Lineage on BLAST
Authors: Zheng Jeffrey , Zhou Yang , Zhu Minghan , Qiao Mu , Zhang Zhigang
Published: February 2021

COVID-19 patients worldwide are conveniently described by position information to collect samples, and modern GIS maps are useful to show influenced flows and numbers of patients on various regions of a pendamic. From an analysis viewpoint, it is more interesting to organize genomic information into a phylogenic tree with multiple branches and leaves in representations. Clusters of genomes are organized as phylogenic trees to represent intrinsic information of genomes. However, there are structural difficulties in projecting phylogenetic information into 2D distributions as GIS maps naturally.Considering advanced generating schemes of phylogenetic trees, information entropy provides ultra optimal properties in the minimum computational complexity, superior flexibility, better stability, improved reliability and higher quality on global constructions.In this paper, a novel projection is proposed to arrange SARS-CoV-2 genomes by genomic indexes to make a structural organization as 2D GIS maps. For any genome, there is a unique invariant under certain conditions to provide an absolute position on a specific region. In this hierarchical framework, it is possible to use a visual tool to represent any selected region for clustering genomes on refined effects. Applied diversity measure to a given set of genomes, equivalent clusters and complementary visual effects are provided between genomic index maps and phylogenetic trees. Sample genomes of three UK new lineages are aligned by BLAST as a basis on both RNA-dependent RNA polymerase RDRP segments and whole genomes. Selected regions and various projections show spread effects of five thousand SARS-CoV-2 genomes in 72 countries on both RDRP and whole genomes, and six special countries/regions are selected on genomic index maps.Based on genomic index maps, one SNV of two genomes on B.1.1.7 lineage can be identified from a unit of 10^4 probability measure to a unit of 10^6 difference for genomic indexes on a special ‘G’ projection to extract the finest variation.Further exploration on optimal classification and phylogenetic analysis of genomic index maps and phylogenetic trees on SARS-CoV-2 genomes worldwide are discussed.
Influence of GSTT1 and GSTP1 polymorphisms on type 2 diabetes mellitus and diabetic retinopathy risk in the Chinese population: a case control study
Authors: Geng Xinqian , Zha Ling , Xiong Yuxin , Xu Fan , Xu Bo , Wang Feiying , Wang Xiaoling , Yang Ke , Tao Wenyu , Li Yiping , Zhou Taicheng , Yang Ying
Published: February 2021

Background: Studies have revealed the association of glutathione S-transferases (GSTM1 and GSTT1) deletion (null) polymorphism with the risks of developing type 2 diabetes mellitus (T2DM) and its complications. The present study aimed to investigate the relationship between GSTT1/ GSTP1 gene polymorphisms and the risks of T2DM and diabetic retinopathy (DR) in a Chinese population.Methods: In this case-control study, a total of 336 subjects with T2DM and a defined ophthalmologic status were recruited from the Second People’s Hospital of Yunnan Province between June 2014 and October 2016. Seventy-two age-matched healthy controls were also enrolled. Physical examinations and laboratory tests were performed. The frequencies of GSTT1 genotypes in all participants were determined by polymerase chain reaction (PCR) followed by agarose gel electrophoresis. Genotyping of GSTP1 gene was identified by PCR amplification followed by sequencing.Results: Compared with healthy controls, the GSTT1-null genotype was significantly more common in diabetic patients with or without DR (all P < 0.05). However, there was no difference in the frequencies of the GSTP1 genotype (AA, GA, GG) between diabetic patients with or without DR and healthy controls. Furthermore, neither the GSTP1 nor GSTT1 genetic polymorphism was associated with the development of DR. In the present study, the risk of developing T2DM was significantly higher in subjects carrying the combined heterozygous GSTP1 (AG) and null GSTT1 genotypes (OR = 0.40, 95% CI = 0.21-0.74, P = 0.02).Conclusions: The deletion of the GSTT1 genotype was associated with a higher risk of developing T2DM, whether alone or in combination with GSTP1, indicating that the null genotype of GSTT1 may serve as a potential biomarker for T2DM in the Chinese population, which is helpful for clinicians to make more effective risk-based decisions.