bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioactivity of Recombinant Humanized Monoclonal Antibody Against HER2 and Its Mechanism of Action on Ovarian Cancer
Authors: Zeng Jinfeng , Zhang Rui , Guan Rui
Published: October 2021

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) protein is overexpressed on the surface of various epithelial ovarian cancer tissues, which mediates the proliferation, differentiation, metastasis and signal transduction of tumor cells and is a potential cancer therapeutic target.METHODS: In this paper, the recombinant anti-HER2 humanized IgG1 monoclonal antibody (rhHer2-mAb) was expressed in HEK293F cells by constructing mammalian cell expression vector and optimizing transfection conditions. The antibody was purified by rProtein A affinity chromatography, and its mediated antibody dependent cytotoxicity (ADCC) was identified by lactate dehydrogenase(LDH) lactate dehydrogenase release assay. The anti-tumor activity of rhHer2-mAb was evaluated in NOD/SCID mice. RESULTS: The expression of rhHer2-mAb in HEK293F cells was at the highest level (100.5 mg/L) when the ratios of DNA/PEI and light chain/heavy chain was 1:4 and 1:2, respectively. The IC50 on ADCC of antibodies against SK-OV-3, OVCAR-3 and A-2780 cells were 12.36, 5.43 and 102.90ng/ml, respectively. Animal experiments in mice showed that rhHer2-mAb could effectively inhibit the growth of SK-OV-3 tumor at the dose of 10 mg/kg.CONCLUSIONS: The recombinant monoclonal antibody was obtained by transient gene expression technology and its bioactivity was studied in vitro and in vivo , providing a novel insight for the development and production of future biotechnology-based drugs using transient gene expression technology of HEK293F.
A Rapid Antibody Screening Haemagglutination Test for Predicting Immunity to Sars CoV-2 Variants of Concern
Authors: Ertesvåg Nina Urke , Xiao Julie , Zhou Fan , Ljostveit Sonja , Sandnes Helene , Jalloh Sarah Lartey , Saevik Marianne , Hansen Lena , Madsen Anders , Mohn Kristin , Fjelltveit Elisabeth , Olofsson Jan Stefan , Tan Tiong Kit , Rijal Pramila , Schimanski Lisa , Øyen Sir , Dunachie Susanna , James William , Harding Adam , Harvala Heli , Jämsén Anni , Roberts David , Zambon Maria , group PHE Virology , Broksatd Karl , group Oxford Collaborative , Townsend Alain , Langeland Nina ,   Bergen COVID-19 Research Group, Cox Rebecca
Published: October 2021

Evaluation of susceptibility to emerging SARS-CoV-2 variants of concern (VOC) requires rapid screening tests for neutralising antibodies which provide protection. We developed a receptor-binding domain specific hemagglutination test (HAT) which correlated with neutralising antibodies (R=0.74-0.82) in two independent cohorts from 798 convalescents. Home-dwelling older individuals (80-99 years, n=89) had significantly lower antibodies after one dose of BNT162b2 vaccine than younger adult vaccinees (n=310) and naturally infected individuals (n=307). The second vaccine dose boosted and broadened the antibody repertoire to VOC in naïve but not previously infected, older and younger adults. >75% of older adults responded after two vaccinations to alpha and delta, but only 59-62% to beta and gamma, compared to 96-97% of younger vaccinees and 68-76% of infected individuals. Overall, the HAT provides a surrogate marker for neutralising antibodies, could be used as a simple inexpensive, rapid test, rapidly adaptable to emerging VOC for large-scale evaluation of potentially diminishing vaccine effectiveness.
Application of An Exponential Mathematical Law of Cardiac Dynamics In 16 Hours
Authors: Velásquez Javier Oswaldo Rodríguez , Herrera Sandra Catalina Correra , Gómez Yesica Tatiana Beltrán , Rojas Jorge Gómez , Bohórquez Signed Esperanza Prieto , Correa Dharma Rodríguez , Rodríguez Sefirot , Guardiola Guillermo Trout , Cruz Ediltrudis Ramos de la , Guezguan Alexander
Published: October 2021

Introduction and objectives: nonlinear dynamics and fractal geometry have allowed the advent of an exponential mathematical law applicable to diagnose cardiac dynamics in 21 hours, however, it would be beneficial to reduce the time required to diagnose cardiac dynamics with this method in critical scenarios, in order to detect earlier complications that may require medical attention. The objective of this research is to confirm the clinical applicability of the mathematical law in 16 hours, with a comparative study against the Gold Standard. Methods: There were taken 450 electrocardiographic records of healthy patients and with cardiac diseases. A physical-mathematical diagnosis was applied to study cardiac dynamics, which consists of generating cardiac chaotic attractors based on the sequence of heart rate values during 16 hours, which were then measured with two overlapping grids according to the Box-Counting method to quantify the spatial occupation and the fractal dimension of each cardiac dynamic, with its respective statistical validation. Results: The occupation spaces of normal dynamics calculated in 16 hours were compatible with previous parameters established, evidencing the precision of the methodology to differentiate normality from abnormality. Sensitivity and specificity values of 100% were found, as well as a Kappa coefficient of 1. Conclusions: it was possible to establish differences between cardiac dynamics for 16 hours, suggesting that this method could be clinically applicable to analyze and diagnose cardiac dynamics in real time.
NLRP3 is a Novel Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma and Skin Cutaneous Melanoma
Authors: Yuan Chenxi , Wang Qingwei , Dai Xueting , Song Yipeng , Yu Jinming
Published: October 2021

Background: Lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) are common tumors around the world. However, the prognosis in advanced patients is poor. Because NLRP3 was not extensively studied in cancers, so that we aimed to identify the impact of NLRP3 on LUAD and SKCM through bioinformatics analyses. Methods: TCGA and TIMER database were utilized in this study. We compared the expression of NLRP3 in different cancers and evaluated its influence on survival of LUAD and SKCM patients. The correlations between clinical information and NLRP3 expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in were analyzed by Cox regression. In addition, we explored the correlation between NLRP3 and immune infiltrates. GSEA and co-expressed gene with NLRP3 were also done in this study. Results: NLRP3 expressed disparately in tumor tissues and normal tissues. Cox regression analysis indicated that up-regulated NLRP3 was an independent prognostic factor for good prognosis in LUAD and SKCM. Logistic regression analysis showed increased NLRP3 expression was significantly correlated with favorable clinicopathologic parameters such as no lymph node invasion and no distant metastasis. Specifically, a positive correlation between increased NLRP3 expression and immune infiltrating level of various immune cells was observed. Conclusion: Together with all these findings, increased NLRP3 expression correlates with favorable prognosis and increased proportion of immune cells in LUAD and SKCM. These conclusions indicate that NLRP3 can serve as a potential biomarker for evaluating prognosis and immune infiltration level.
3D Mapping of Intra-articular Calcaneal Fractures
Authors: Shi Guang , Zhan Hongrui , Liu Wei , Zhang Tao , Lin Zhao , Liao Xun , Cai Xiyu
Published: October 2021

Background: The management of intra-articular calcaneal fractures (ICFs) still faces a challenge. Available research about the anatomic patterns of ICFs is lacking. We aimed to define the pattern of ICFs by a three-dimensional (3D) mapping and determine whether there are consistent fracture patterns and comminution zones. Methods: 67 patients of ICFs with available computed tomographic (CT) scans were identified. The calcaneal fractures fragments on CT were multiplanar reconstructed and virtually reduced. 3D heat mapping was subsequently created by graphically superimposing all fracture lines onto a standard calcaneal template. Mapping of fracture lines and comminution zones in both the axial and sagittal planes were performed. Results: The cohort included 26 (38.8%) left calcaneal fractures, 27 (40.30%) right calcaneal fractures, and 14 (20.9%) cases with bilateral fractures. Comminuted fractures accounted for 92.5% of all fractures. Sagittal 3D mapping demonstrated that fracture lines were concentrated in the critical angle of Gissane and extended posteriorly to the rear of the tuberosity of the lateral wall and the anterior of the medial process of the calcaneus tuberosity but with more significant variation in the medial wall. The mean angle of fracture lines concerning the long axis of the calcaneal (LAC) was 29.1°and 19.2° in the lateral wall and medial wall, respectively. Axial 3D mapping demonstrated that fracture lines were primarily concentrated in the area anterior to the posterior joint facet and extended along the posterior joint facet and calcaneus sulcus to the posteriorly of the tuberosity. The mean angle of fracture lines concerning the LAC was 11° in the axial wall. 3D mapping demonstrated that the comminution zones are closely related to the internal structure and fracture mechanism. Conclusion: The data presented have elucidated there are consistent characteristic fracture patterns and comminution zones for ICFs. This study provides visual guidelines to understand fracture morphology, which may assist with fracture classification, preoperative planning, fixation concepts development, and internal structure analysis.
Synthesis, and Biological Evaluations of Novel Pyrazinoic Acid Derivatives as Anticancer Agents
Authors: Akhlaghi Shiva , mostoufi Azar , kalantar Hadi , Fereidoonnezhad Masood
Published: October 2021

Pyrazinoic acid or pyrazine-2-carboxylic acid (PA), due to its nitrogenous heteroaromatic ring, can be explored as an anticancer agent. Here, a series of twenty novels PA derivatives have been synthesized and characterized using IR, NMR, and mass spectrums. Their cytotoxic activity was evaluated against three different cancer cell lines, including lung (A549), breast (MCF-7), and colon (HT-29). P16, the most potent compound, showed moderate cytotoxicity with IC50 of 6.11 μM, 10.64 μM, and 14.92 μM, against the A549, MCF-7, and HT-29 cell lines, respectively. Furthermore, the effect of this compound against MRC5 as a non-tumoral lung cell line, exhibited a selectivity index of 9.02. The apoptotic induction activity of P16 was also performed on the A549 cell line. The results showed that as the concentration of the compound increases (from 3 to 6 μM), the percentage of induction of apoptosis increases from 8.54% to 72.4%. Electrophoretic gel mobility shift assays showed that P16 was also able to ROS induce DNA cleavage in the presents of H2O2 (1.0 mM) in dose-dependent manner. Molecular docking was also applied to anticipate the binding locations and the binding of the synthesized compound with Bcl-2 apoptosis regulator and DNA as their proposed targets.
Encoding and retrieval of associative recognition memory engage different sub-networks within a hippocampal-thalamo-cortical memory circuit
Authors: Barker Gareth , Tran Stephanie , Gilroy Kerry , Bashir Zafar , Warburton Elizabeth
Published: October 2021

Recognition of previously encountered stimuli and their associated spatial and temporal information depends on neural activity within a brain-wide network in which the CA1 region of the hippocampus, nucleus reuniens of the thalamus (NRe) and medial prefrontal cortex (mPFC) are key nodes. However, the pathways crucial for coordinating activity during memory encoding and/or retrieval phases have been little explored. Here we opto- or chemo associative recognition memory. We discovered that encoding, but not retrieval depended on the CA1 to mPFC and NRe to mPFC projections. In contrast, retrieval depended on the mPFC to NRe projection. Interestingly the NRe to CA1 pathway was required for both memory phases. Our findings therefore reveal that encoding and retrieval engage dissociable sub-networks within a hippocampal-thalamo-cortical recognition memory circuit in order to enable binding of recent and related information, whilst ensuring a separation of processing.
Assessing The Long- and Short-Run Asymmetrical Effects of Climate Change On Rice Production: Empirical Evidence From India
Authors: Baig Imran Ali , Chandio Abbas Ali , Ozturk Ilhan , Kumar Pushp , Khan Zeeshan Anis , Salam Md. Abdus
Published: October 2021

For a couple of decades, environmental change has arisen as a ubiquitous problem and gained environmentalist's attention across the globe due to its long-term harmful effect on agricultural production, food supply, water supply and livelihoods of rural poor. The primary objective of this study is to explore the asymmetrical dynamic relationship between climate change and production of rice and controlled variables covering 1991–2018 by employing the nonlinear autoregressive distributed lag (NARDL) model and Granger causality approach.in India. The NARDL findings demonstrate a significant negative relationship between mean temperature and production of rice in the long run while positively influencing rice production in the short run. Moreover, positive shocks in rainfall and carbon emission have a negative and significant effect on India's rice production in the long and short run. In comparison, negative shock in rainfall has a significant positive impact on rice production in the long and short run. Wald test confirms the asymmetrical relationship between climate change and rice production. The Granger causality test shows feedback effect among mean temperature, decreasing rainfall, increasing carbon emission, and rice production. While no causal relationship between increasing temperature and decreasing carbon emission. Based on our empirical investigations, some critical policy implications emerged. To sustain rice production, improve irrigation infrastructure through increasing public investment and develop climate-resilient seeds varieties to cope with climate change. Along with, at the district level government should provide proper training to farmers regarding the usage of pesticides, proper amount of fertiliser and irrigation systems.
Effect of Total Anthocyanin-base Standardized Cornus Mas L. Fruit Extract on Hepatic Steatosis and Visceral Adiposity Index in Patients With Non-alcoholic Fatty Liver Disease: a Double-blind Randomized Controlled Trial
Authors: Sangouni Abbas Ali , Hosseinzadeh Mahdieh , Sangsefidi Zohreh Sadat , Yarhosseini Faezeh , Akhondi-Meybodi Mohsen , Ranjbar Alimohammad , Madadizadeh Farzan , Mozaffari-Khosravi Hassan
Published: October 2021

Background:Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Experimental evidence has proposed the beneficial effects of Cornus mas L. (cornelian cherry) extract, as a rich source of anthocyanins, on steatosis and central obesity. However, very few clinical trials were conducted in this regard. We investigated the effect of total anthocyanin-base standardized cornelian cherry fruit extract on hepatic steatosis index (HSI) and NAFLD liver fat score (NAFLD-LFS), and visceral adiposity index (VAI) in patients with NAFLD.Methods:The present study was conducted as a double-blind, randomized controlled clinical trial among 50 subjects suffering from NAFLD. Subjects were randomly assigned to receive cornelian cherry extract (20 cc/d, which provides 320 mg/d total anthocyanin) or placebo for 12 weeks.Results:There was no difference between the two groups in HSI, NAFLD-LFS and VAI at the baseline. After 12-week intervention, cornelian cherry extract compared to the placebo demonstrated no significant effect on HSI (change: -0.9 ± 3.5 vs. -1.2 ± 3.2; P = 0.72), NAFLD-LFS (change: 0.2 ± 1.3 vs. 0.1 ± 0.7; P = 0.62), and VAI (change: 0.05 ± 0.7 vs. 0.07 ± 1.0; P = 0.94).Conclusion:Cornelian cherry extract (20 cc/d) for 12 weeks has no effect on steatosis and visceral obesity. To better conclude, further trials with longer intervention durations are required. Trial registration: The study protocol was registered on 30 September 2018 at Iranian Registry of Clinical Trials under code IRCT20180419039359N1 (https://www.irct.ir/trial/30707).
Plate motion drives variability in ocean oxygenation through the Phanerozoic
Authors: Pohl Alexandre , Ridgwell Andy , Stockey Richard , Thomazo Christophe , Keane Andrew , Vennin Emmanuelle , Scotese Christopher
Published: October 2021

The early evolutionary and much of the extinction history of marine animals, is thought to be driven by changes in dissolved oxygen concentrations ([O2]) in the ocean1–3. In turn, [O2] is widely assumed to be dominated by the geological history of atmospheric oxygen (pO2)4,5. Here, in contrast, we show via a series of Earth system model experiments how continental rearrangement during the Phanerozoic drives profound variations in ocean oxygenation and induces a fundamental decoupling in time between upper-ocean and benthic [O2]. We further identify the presence of (paleogeographical) state-dependent modes of circulation instability (oscillations), which allows for pO2 to already be close to modern by the beginning of the Phanerozoic despite the deep ocean remaining anoxic. The occurrence of extreme volatility in ocean oxygenation also provides a causal mechanism explaining elevated rates of metazoan radiation and extinction during the early Paleozoic6. The absence in our modelling of any simple correlation between global climate and ocean ventilation together with the occurrence of profound variations in ocean oxygenation independent of atmospheric pO2, presents both a challenge to the interpretation of marine redox proxies, but also points to a hitherto unrecognized role for continental configuration in the evolution of the biosphere.
Oocytes with smooth endoplasmic reticulum aggregates do not impact blastocyst euploidy rate
Authors: Xu Jian , Yang Li , Chen Zhi-Heng , Yin Min-Na , Chen Juan , Sun Ling
Published: October 2021

Objective: To investigate whether the euploidy rate of blastocysts derived from smooth endoplasmic reticulum (SERa) positive cycles and oocytes are impacted.Design: Retrospective cohort study.Setting: A tertiary hospital-based reproductive medicine center.Patient(s): A total of 601 preimplantation genetic testing (PGT) cycles with obtained oocytes in our center between April 2017 and May 2021 were included in the study. Intervention(s): Women＞35 years and PGT cycles with chromosomal structural rearrangements (PGT-SR) were excluded. Embryological and blastocyst ploidy outcomes were compared between SERa+ oocyte, sibling SERa- oocytes and oocytes in SERa- cycles.Main Outcome Measure(s): Embryological outcomes and blastocyst euploidy rate.Results: No significant difference was observed in the normal fertilization rate (82.1 % vs. 77.8 % vs. 83.1 %, respectively, P=0.061), blastocyst formation rate (71.0 % vs. 72.5 % vs. 68.4 %, respectively, P=0.393), good quality blastocyst formation rate (46.4 % vs. 48.3 % vs. 42.6 %, respectively, P=0.198) between the SERa+ oocyte group, sibling SERa- oocyte group and SERa- oocyte group. No significant difference was observed in the euploidy rate (50.0 % vs. 62.5 % vs. 63.3 %, respectively, P=0.324), mosaic rate (12.5 % vs. 9.7 % vs. 13.4 %, respectively, P=0.506) and aneuploidy rate (37.5 % vs. 27.8% vs. 23.2 %, respectively, P=0.137) between the three groups.Conclusion: Our results suggest that the euploidy rate of blastocysts derived from SERa+ cycles and oocytes are not impacted.
Metabolic Profiling and Inhibitory Properties of Different Parts of Salsola Vermiculata Towards Acetylcholinesterase and α-glucosidase
Authors: Mollaei Saeed , Farnia Poopak , Ghanavi Jalaledin
Published: October 2021

Background: Herbal and natural medicines play significant roles in treatment of diseases and development of novel drugs. Salsola vermiculata is an annual plant which is broadly distributed in southwest of Asia, and is used for treatment of stomach disorders. Results: This present study aimed at identifying and comparing the metabolic profiles of different parts of Salsola vermiculata and to evaluate the inhibitory potential of their extracts and fractions towards acetylcholinesterase and α-glucosidase. LC-ESI-MS, GC, and GC-MS analytical methods were employed for metabolite profiling of the extracts, and their fractions. The α-glucosidase and acetylcholinesterase inhibitory activities of the samples were determined by microplate colorimetric methods. Based on results, 44 metabolites were identified in different parts of S. vermiculata. In roots, vanillic acid, rutin, salsoline, salsoline A, palmitic acid, oleic acid, linoleic acid, cumin aldehyde, and carvone; in seeds, vanillic acid, salsoline A, palmitic acid, oleic acid, linoleic acid, carvone, and β-caryophyllene; in leaves, gallic acid, vanillic acid, caffeic acid, rosmaric acid, rutin, quercetin, limonene, and carvone, and in flowers, gallic acid, vanillic acid, cinnamic acid, rosmaric acid, rutin, kaempferol, limonene, linalool, and carvone were recorded as the main components. According to the inhibitory activities results, the ethyl acetate fractions of leaves and the aqueous-acid fraction of roots displayed highest inhibitory activity towards acetylcholinesterase (IC50: 17.24 µg/mL), and α-glucosidase (IC50: 62.37 µg/mL), respectively. Conclusion: Finally, the leaves and roots of S. vermiculata are rich of phenolic and alkaloids compounds and the findings of this study depict them as a promising acetylcholinesterase and α-glucosidase inhibitors, and therefore, can be utilized for the development of new drugs.
Municipal Solid Waste Management Practice in Yirgalem Town, Sidam Region, Ethiopia
Authors: Teshome Yirdaw Meride , Habtu Nigus Gabbiye , Molla Mikias Biazen , Ulsido Mihret Dananto
Published: October 2021

Background: Municipal solid waste is not properly treated and handled in less developed countries such as Ethiopia. Consequently, it pollutes the air, groundwater, and soil, which results in a negative impact on the hygienic conditions of the people, and the environment. This study aimed to assess existing municipal solid waste management practices in Yirgalem Town. Result: The survey result revealed that 73.2 % of the participants considered their surroundings clean and 83% of the respondents knew more about solid waste management. This result showed that only 38% of the households have access to door -to- door solid waste collection services in the Town. Yirgalem Town does not have a well managed municipal solid waste disposal site, thus every waste generated from the town is discarded into an open dumping area. More than 50.9% of the respondents feel unsatisfied with the current solid waste management services. Most solid waste management practices (knowledge, recycling and reusing, participation, and sorting and disposal practices) are significantly associated with gender, age and monthly income level of socio-demographic characteristics (p <0.05). However, other socio-demographic characteristics such as marital status, educational background, and job status and house ownership were not significantly associated with solid waste management practices. (p > 0.05). Conclusion: In general, poor institutional structure, lack of skilled manpower, finance and equipment and tools are the major challenges faced by the municipality of Yirgalem Town. Thus, an integrated and inclusive solid waste management system is required to strengthen future waste management strategies and policies.
Outdoor Public Recreation Spaces And Social Connectedness Among Adolescents
Authors: Rivera Elise , Veitch Jenny , Loh Venurs HY , Salmon Jo , Cerin Ester , Mavoa Suzanne , Villanueva Karen , Timperio Anna
Published: October 2021

Background: Outdoor public recreation spaces are important settings for leisure and physical activity. Adolescents’ use of these spaces may be related to their social connectedness; however, research on this topic is limited. This study examined associations of frequency of visitation and physical activity in outdoor public recreation spaces with social connectedness among adolescents in Melbourne, Australia. Methods: Adolescents self-reported their frequency of visitation to parks, trails, beach/lake, and sports facilities; frequency of physical activity in a park, local street or path, and their street; and social connectedness. Separate analyses were conducted for visitation (n=349, 15.4±1.6 years, 58% female) and physical activity (n=441, 15.4±1.6 years, 59% female) using multilevel linear regression models. Results: No significant associations were observed for frequency of visitation to a park (B = 0.86, 95% CI= -0.26, 1.99), trails (B = 0.41, 95% CI= -0.61, 1.44), beach/lake (B = -0.44, 95% CI= -1.46, 0.57), or sports facilities (B =0.64, 95% CI= -0.43, 1.70), nor for frequency of physical activity in their street (B = -0.07, 95% CI= -0.46, 0.31), local streets/paths (B = -0.05, 95% CI= -0.43, 0.33) or in parks (B = 0.23, 95% CI= -0.14, 0.60) with adolescents’ social connectedness. Conclusions: The findings did not support the hypothesis that visiting and being active in outdoor public recreation spaces are associated with adolescents’ social connectedness. Future research should consider the duration and context of outdoor public recreation space use (e.g., sports, socialising, relaxing alone) and whether different types and/or a combination of public spaces are more/less conducive to social connectedness.
Social Isolation Induces Neuroinflammation And Microglia Overactivation, While Dihydromyricetin Prevents And Improves Them.
Authors: Omran Alzahra J Al , Shao Amy S , Watanabe Saki , Zhang Zeyu , Zhang Jifeng , Xue Chen , Watanabe Junji , Davies Daryl L. , Shao Xuesi M. , Liang Jing
Published: October 2021

Background: Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country's mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment-resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system.Methods: Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety like behaviors after DHM treatment were examined using elevated plus maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. Results: Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation also induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes.Conclusion: The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to restore neuroinflammatory changes induced by anxiety.
A Retrospective Study Assessing the Risk Factors of Type 2 Diabetes Mellitus Linked to Diabetic Foot Ulcer Incidence in Jiaxing, China
Authors: Zhou Qiang , Mao Minjie , Shao Yichuan , Yu Danlu , Tang Shengjie , Yang Yinling , Xu Chenggao
Published: October 2021

Objective: Diabetic foot (DF) is one of the common serious complications of diabetes, which is an important cause of death and disability, and is associated with diabetic vascular disease and diabetic neuropathy. The purpose of this study was to assess the incidence and risk factors for diabetic foot among a diabetic population. Methods: The study was a retrospective cohort review. The population studied was 348 male examinees of type 2 diabetes mellitus (DM), in which age-matched equal examinees (174 patients each) were with diabetic foot (DF Group) and with no indication of diabetic foot (non-DF group), hospitalized in the same year at The First Hospital of Jiaxing, China. Medical records were reviewed to collect clinical profile, including duration of disease, smoking, previous diabetic foot incidence, and medication (such as metformin). Categorical data between groups were analyzed using chi-square test (χ2). Unconditional logistic regression analysis was used for multi-factor analysis to identify the risk factors of diabetic foot. Results: Comparing the baseline data of DF Group and non-DF Group, age, course of disease, LDL-C and use of metformin showed no significant difference (P >0.05). The results of the logistic regression analysis showed that smoking history (OR=1.88, P=0.020), previous diabetic foot history (OR=2.290, P=0.016), Hcy (OR=1.194, p≤0.001) were independent risk factors for diabetic foot disease, and HgB (OR =0.984, P=0.021) was the protective factor of diabetic foot disease in male subjects. Age (OR=0.985, P=0.304), course of disease (OR=1.048, P=0.233), history of metformin use (OR=0.851, P=0.509), HbA1c (OR=1.302, P=0.059), LDL-C (OR=0.936, P=0.698), Creatinine (OR =1.010, P=0.326), and ALB (OR =0.943, P=0.084) were not significantly correlated with diabetic foot disease. Conclusions: Smoking, previous diabetic foot history, and homocysteine are independent risk factors for diabetic foot disease. HgB is the protective factor of diabetic foot disease in male patients.
Isolation and Screening of Antagonistic Actinomycetes for Potential Application in The Control of Pathogenic Bacteria in Contaminated Waste
Authors: Dahdah Kamal , Nourine Heidar , Boughambouz Amel , Sebti Sarra , Bouchaala Laid , Nabti El-hafid
Published: October 2021

Purpose

Organic wastes for agricultural use represents a real agronomic interest but also a risk for public and animal health. Actinomycetes present a potential source of bioactive compounds with multiple applications.
Methods

Among the 88 isolates of actinomycetes obtained from different samples, we selected a strain identified, thanks to macro- and microscopic characters, as Streptomyces sp. SCM21. This strain showed these potentialities to produce antibacterial metabolites against the pathogenic bacteria tested (S. aureus, B. cereus and S. enteritidis) when cultivated in liquid and solid fermentation. Solid-state fermentation was conducted using sewage sludge as substrate.
Results

This is the first time that sewage sludge has been used to produce antibacterial metabolites by a strain of actinomycetes in solid-state fermentation. In addition, solid-state fermentation moistened with distilled water gave better antibacterial activity with good sporulation of Streptomyces sp. CSM21.
Conclusion

The product of solid-state fermentation can be used in the management of contaminated waste to control pathogenic bacteria.
The effective interventions to improve long-term physiotherapy exercise adherence among patients with lower limb osteoarthritis. A systematic review
Authors: Cinthuja Pathmanathan , Krishnamoorthy Nidhya , Shivapatham Gamalendira
Published: October 2021

Introduction: Osteoarthritis (OA) is a chronic condition that severely effects work life balance impacting psychosocial and socio-economic aspects. Physiotherapy exercise is one of the intervention methods for the management of OA. Adherence to the exercise by patients is essential for the effective management of OA. Objectives: To determine different methods used to enhance physiotherapy exercise adherence for more than 12 months among patients with osteoarthritis and to report the effective method to enhance exercise adherence among people with lower limb osteoarthritis. Design: Systematic review Methods: PubMed, Pedro, Web of Science, and EMBASE databases searched for randomized controlled trials, cohort studies, case-control studies, and cross-sectional studies published in the English language from 2000 to 2020. The date of data extraction was 04 September 2020. Two independent researchers conducted literature search, assessed eligibility, extracted data, conducted methodology quality assessment using the PEDro scale, and conducted risk of bias assessment. A narrative synthesis of key outcomes is presented; preferred Reporting Items for Systematic review was used to report the review. The study protocol was registered in the Prospero (Prospero ID: CRD42020205653). Results: The primary search strategy identified 5839 potentially relevant articles, of which 5157 remained after discarding duplicates. After screening based on title and abstract, 40 papers were potentially eligible for inclusion. Five of these papers met all predefined eligibility criteria. Introducing methods to enhance exercise adherence has caused a significant increase in exercise adherence for the short term (less than six months or 12 months). There were no significant differences, long-term adherence with different methods, reported. The results indicate that booster sessions (89.69%) and telephone-linked communication (86%) had higher percentages for the exercise adherence. Secondary outcomes such as pain, stiffness, function, show positive outcomes with increasing exercise adherence. However, there were no significant differences reported. Conclusion: The booster sessions and telephone-linked communication appear to enhance exercise adherence for more than 12 months among patients with osteoarthritis. However, a number of high-quality studies are inadequate to confirm our findings. Therefore, more studies with higher methodological quality are needed to determine the best strategies to enhance long-term exercise adherence among people with osteoarthritis. Key terms: Osteoarthritis, Long term, Exercise adherence
Cryo-EM structures reveal the electromotility mechanism of prestin, the cochlear amplifier
Authors: Futamata Haon , Fukuda Masahiro , Umeda Rie , Yamashita Keitaro , Takahashi Satoe , Shikakura Takafumi , Hayashi Shigehiko , Homma Kazuaki , Nishizawa Tomohiro , Nureki Osamu
Published: October 2021

Outer hair cell electromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, we report the cryo-EM structures of thermostabilized human prestin (hPresTS), complexed with chloride, sulfate, or salicylate at 3.52–3.61 Å resolutions, revealing a crossed dimeric arrangement. The central positively-charged cavity allows flexible binding of various anion species, resulting in distinct modulations of nonlinear capacitance (NLC), playing an important role in electromotility. Comparisons of these hPresTS structures suggest rigid-body movement between the core and gate domains, and provide mechanistic insight into prestin inhibition by salicylate. Mutations at the dimeric interface severely diminished NLC, suggesting that stabilization of the gate domain facilitates core domain movement, thereby contributing to the expression of NLC. These findings advance our understanding of the molecular mechanism underlying mammalian cochlear amplification.
Advanced Optimal Control-Based Design of a Gough-Stewart Platform
Authors: Zhu Minglei , Song Shijie , Gong Dawei
Published: October 2021

Designing a robot with the best accuracy is always the attractive research direction in robot community. In order to create a Gough-Stewart platform with guaranteed accuracy performance for a dedicated controller, this paper describes a novel advanced optimal design methodology: control-based design methodology. This advanced optimal design method considers the controller positioning accuracy in the design process for getting the optimal geometric parameters of the robot. In this paper, three types of visual servoing controllers are applied to control the motions of the Gough-Stewart platform: leg-direction-based visual servoing, line-based visual servoing and image moment visual servoing. Depend on these controllers, the positioning error models considering the camera observation error together with the controller singularities are analyzed. In the next step, the optimization problems are formulated in order to get the optimal geometric parameters of the robot and the placement of the camera for the Gough-Stewart platform for each type of controller. Then, we perform the co-simulations on the three optimized Gough-Stewart platforms in order to test the positioning accuracy and the robustness with respect to the manufacturing errors. It turns out that the optimal control-based design methodology helps getting both the optimum design parameters of the robot and the performance of the controller {robot + dedicated controller}.
Identification of a Promiscuous Conserved CTL Epitope Within the SARS-CoV-2 Spike Protein
Authors: Jiang Sheng , Wu Shuting , Zhao Gan , He Yue , Guo Xinrong , Zhang Zhiyu , Hou Jiawang , Ding Yuan , Cheng Alex , Wang Bin
Published: October 2021

The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC‑I and MHC‑II epitopes by ELIspot and cytolytic assays to a conserved MHC‑I epitope. The epitope is highly conserved in current viral variants and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.
Where Do the World’s Squirrel Hotspots and Coldspots of 230+ Species Go with Climate Change 2100? A First BIG DATA Minimum Estimate from an Open Access Climate Niche Rapid Model Assessment
Authors: Steiner Moriz , Huettmann Falk
Published: October 2021

Man-made climate change and its impact on the living world remain the problem of our time waiting for a good science-based resolution. Here, we focus on forecasting the global squirrel population as a representative but overlooked species group for the year 2100. This was possible by using 230 publicly available Species Distribution Model prediction maps for the world’s squirrels (233 out of 307; 75%). These distribution forecasts are originating from 132 GIS predictors, implemented with an ensemble of three machine learning algorithms (TreeNet, RandomForest, and Maxent). We found that most of the world’s squirrel ranges will be shifting (usually towards higher altitudes and latitudes) and remain/ become more fragmented; some species extend their range, and many can ‘spill’ into new landscapes. Considering that here we just ran a Rapid Assessment of Big Data, dealing with a climate niche envelope of the future but not the entire more holistic perspective of climate change and 2100, we assume wider serious changes will occur for squirrels, their habitats, and the world in the future Anthropocene of 2100. These changes can lead to more stress, genetic loss, extinction, and increased zoonotic disease transmissions, and this process will occur with an increased gradient over time.
Osteoclast-Derived Extracellular miR-106a-5p Promotes Osteogenic Differentiation and Facilitates Bone Defect Healing
Authors: Wu Yutong , Ai Hongbo , Zou Yuchi , Xu Jianzhong
Published: October 2021

Small extracellular vesicles (sEVs) are considered to play critical roles in intercellular communications during normal and pathological processes since they are enriched with miRNAs and other signal molecules. In bone remodeling, osteoclasts generate large amounts of sEVs. However, there is very little research about whether and how osteoclast-derived sEVs (OC-sEVs) affect surrounding cells. In our study, microarray analysis identified miR-106a-5p highly enriched in OC-sEV. Further experiments confirmed that OC-sEVs inhibited Fam134a through miR-106a-5p and significantly promoted bone mesenchymal stem cell (BMSC) osteogenic mineralization in vitro. Next, we prepared sEV-modified demineralized bone matrix (DBM) as a repair scaffold, and used a calvarial defect mouse model to evaluate the pro-osteogenic activities of the scaffold. In vivo result indicated DBM modified with miR-106a-5p-sEVs showed an enhanced capacity of bone regeneration. This important finding further emphasizes that sEV-mediated miR-106a-5p transfer play critical roles in osteogenesis and indicate a novel communication mode between osteoclasts and BMSCs.
Emergency endovascular treatment using a Viabahn stent graft for upper and lower extremity arterial bleeding: a retrospective study
Authors: Ueda Tatsuo , Murata Satoru , Tajima Hiroyuki , Saito Hidemasa , Yasui Daisuke , Sugihara Fumie , Mizushima Shohei , Mine Takahiko , Kawamata Hiroshi , Hayashi Hiromitsu , Kumita Shin-ichiro
Published: October 2021

BackgroundA Viabahn stent graft (SG) is a heparin-coated self-expandable SG for lower extremity arterial disease that exhibits high flexibility and accuracy in the delivery system. This study aimed to evaluate the short-term efficacy and safety of emergency endovascular treatment (EVT) using a Viabahn SG for upper and lower extremity arterial bleeding (ULEAB).MethodsConsecutive patients with ULEAB who underwent emergency EVT using the Viabahn SG between January 2017 and August 2021 were retrospectively reviewed. The indications for EVT, location of artery, technical success, clinical success, limb ischemia, periprocedural complications, bleeding-related mortality, 30-day mortality, diameter of the target artery, diameter of the SG, neck length, re-bleeding, endoleaks, and patency of the SGs at 1, 3, 6, and 12 months were evaluated.ResultsEVT using Viabahn SG was performed in 22 patients (mean age: 72.0 years; 11 males) and 23 arteries (upper: 6, lower: 17). The indications for EVT were pseudoaneurysm (n=13, 59.1%), extravasation (n=9, 39.1%), and inadvertent arterial cannulation (n=1, 4.3%). The anatomical locations of the 23 ULEAB injuries were the brachiocephalic (1 [4.3%]), subclavian (3 [13.0%]), axillary (1 [4.3%]), brachial (1 [4.3%]), common iliac (4 [17.4%]), external iliac (8 [34.8%]), common femoral (2 [8.7%]), superficial femoral (2 [8.7%]), and popliteal (1 [4.3%]) arteries. The technical and clinical success rates were 100%. The rates of limb ischemia, periprocedural complications, and bleeding-related mortality were 0%, whereas the 30-day mortality rate was 22.7%. The mean diameters of the arteries and SGs were 7.7 and 8.9 mm, respectively. The mean neck length was 20.4 mm. No endoleaks or re-bleeding occurred during the follow-up period (mean: 169 days). Two SG occlusions without limb ischemia occurred in the external iliac artery and brachial artery after 1 and 4 months, respectively. Subsequently, cumulative SG patency was confirmed after 1, 3, 6, and 12 months in 91.7%, 91.7%, 81.5%, and 81.5% of patients, respectively.ConclusionsEmergency EVT using the Viabahn SG for ULEAB was effective and safe according to short-term outcomes. Appropriate size selection and neck length are important for successful treatment. SG patency was good after 1, 3, 6, and 12 months.
Automated Light-Induced Synthesis of 89Zr-Radiolabeled Antibodies for Immuno-Positron Emission Tomography
Authors: Klingler Simon , Holland Jason
Published: October 2021

Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography (PET) imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in <25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our Good Laboratory Practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in <25 min with an overall decay-corrected radiochemical yield of 20.1±2.4% (n=3), a radiochemical purity >99%, and chemical purity >99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.
Is Aryl Hydrocarbon Receptor Antagonism After Ischemia Effective in Alleviating Hepatic Ischemia-Reperfusion Injury in Rats?
Authors: Kwon Jae-Im , Heo Hwon , Chae Yeon Ji , Min Joongkee , Lee Do-Wan , Kim Sang Tae , Choi Monica Young , Sung Yu Sub , Kim Kyung Won , Choi Yoonseok , Woo Dong Cheol , Woo Chul-Woong
Published: October 2021

Aryl hydrocarbon receptors (AhRs) have been reported to be important mediators of ischemic injury in the brain. Furthermore, the pharmacological inhibition of AhR activation after ischemia has been shown to attenuate cerebral ischemia-reperfusion (IR) injury. Here, we investigated whether AhR antagonist administration after ischemia was also effective in ameliorating hepatic IR injury. A 70% partial hepatic IR (45-minute ischemia and 24-hour reperfusion) injury was induced in rats. We administered 6,2',4'-trimethoxyflavone (TMF, 5 mg/kg) intraperitoneally 10 minutes after ischemia. Hepatic IR injury was observed using serum, magnetic resonance imaging-based liver function indices, and liver samples. TMF-treated rats showed significantly lower relative enhancement (RE) values and serum alanine aminotransferase (ALT) and aspartate aminotransferase levels than did untreated rats at three hours after reperfusion. After 24 hours of reperfusion, TMF-treated rats had significantly lower RE values, ΔT1 values, serum ALT levels, and necrotic area percentage than did untreated rats. The expression of the apoptosis-related proteins, Bax and cleaved caspase-3, was significantly lower in TMF-treated rats than in untreated rats. This study demonstrated that inhibition of AhR activation after ischemia was effective in ameliorating IR-induced liver injury in rats.