bluuebunny/crossref_metadata_2025 huggingface dataset:
A More Important Role of Diabetes Mellitus in Mortality in Elderly Critical COVID-19 Patients: a Single-center Retrospective Study
Authors: Li Yuming , Li Xiantao , Zhou Yu , Yang Yi , Yao Yake , Zhou Hua , Hu Dakang
Published: January 2022

BackgroundCOVID-19 has been circulating worldwide since December 2019. However, its independent risk factors of mortality need further insights in elderly critical COVID-19 patients.MethodsTotally 48 elderly and critically ill COVID-19 patients with clear end point were enrolled when the data were collected, with 16 discharged and 32 died. Kaplan-Meier analysis and Cox regression were performed to identify the risk factors of mortality in elderly critical COVID-19 patients. Survival curve was conducted to present the impact of Diabetes Mellitus on mortality. Mann-Whitney U and t tests were used to 39 clinical variates between the survivor and non-survivor groups.ResultsAs Kaplan-Meier analysis confirmed, only three variates Diabetes Mellitus, chronic obstructive pulmonary disease and family aggregation showed significant difference between the survivor and non-survivor groups. However, only variate Diabetes Mellitus presented significance in Cox regression. Higher C-reaction protein, interleukin-2 (IL-2), IL-8 and creatinine were detected in survivor group than non-survivor group, which was reverse to estimated glomerular filtration rate. The other laboratory finding showed no significant difference between survivor and non-survivor groups.ConclusionsDiabetes Mellitus, chronic obstructive pulmonary disease and family aggregation can contribute to mortality by COVID-19 while Diabetes Mellitus also reduces the survival time of elderly and critically ill COVID-19 patients, highlighting the more important role of Diabetes Mellitus. Laboratory findings could not serve as good predictors of death for elderly and critically ill COVID-19 patients.
Shenmai Injection Exerts Neuroprotective Functions by Down-regulating MicroRNA-19a in H 2 O 2 -induced PC12 Cells
Authors: Wu Jing , li zhonghao , dong xiaoke , yuan siyuan , liu jinmin , wang le
Published: January 2022

Background: Acute ischemic stroke (AIS) and following reperfusion therapy-induced cerebral ischemia reperfusion (I/R) injury have been recognized as an important subject of cerebrovascular disease with high mortality. Oxidative stress is an important pathological process of cerebral I/R injury. microRNA-19a (miR-19a) is involved in I/R. As the organ protectant agent, Shenmai Injection (SMI) is widely used in the clinical treatment of cerebral infarction. Purpose: This study aims to explore whether SMI can reduce oxidative stress by regulating miR-19a, thereby treating I/R injury. Methods: The oxidative stress state of PC12 cells was induced by H2O2, and then the cells were cultured with SMI. The therapeutic effect of SMI was evaluated by detecting cellular superoxide dismutase (SOD), malondialdehyde (MDA) and other oxidative markers with the kit. Western blot, PCR, immunofluorescence and other techniques were used to elucidate the potential mechanism of SMI. Results: Cell viability assay results showed that SMI could improve the viability of PC12 cells stimulated by H2O2. Compared with the H2O2 group, after SMI treatment, the contents of MDA and reactive oxygen species (ROS) were significantly reduced, while the activity of SOD was significantly increased, and SMI could reduce apoptosis by increasing the content of adenosine 5'-triphosphate (ATP) in cells and enhancing the mitochondrial membrane potential (∆Ψm). Western blot and qRT-PCR results showed that these effects were partially achieved through the AMPK/Sirt1/PGC-1α pathway. The level of miR-19a was significantly increased in H2O2 group, and SMI could protect the cells by reducing miR-19a. Further investigated the target of miR-19a, and transfected cells with miR-19a mimic and inhibitor respectively. We found that AdipoR2 was a direct target of miR-19a, and miR-19a could inhibit AdipoR2/PI3K/Akt/mTOR pathway. Conclusion:SMI can activate AMPK/Sirt1/PGC-1α and AdipoR2/PI3K/Akt/mTOR pathways by reducing miR-19a levels, and protect PC12 cells stimulated by H2O2.
High Glucose-Induced Vascular Smooth Muscle Cell Proliferation and Migration are Regulated by the miR-34a-Notch1 Pathway
Authors: Zhang Liping , Pan Rongrong , Zhang Qing , Gu Linling , Shi Gongde , Wu Yutao
Published: January 2022

High glucose(HG)-induced excessive proliferation and migration of the media vascular smooth muscle cell(VSMC) are the main pathological characteristics in diabetes related vascular injuries. Previous studies have shown that microRNA-34a (miR-34a) is involved in cancer metastasis, proliferation and invasion and plays an essential role in cardiovascular disease. However, little is known about the regulating role miR-34a in HG-induced proliferation and migration of VSMC. Here we demonstrated that miR-34a was downregulated at different timepoints under HG stimulation. Then, HG induced proliferation and migration was found to be impaired by miR-34a overexpression using transwell, CCK8 and RT-qPCR assays. Furthermore, the HG-induced depression of “contractile” VSMC-specific markers were reversed by the overexpression of miR-34a. Moreover, we confirmed that miR-34a regulated HG-induced VSMC proliferation and migration through its target gene, Notch1, which has been shown to be associated with cell proliferation and migration in previous studies. Taken together, we propose that the miR34a-Notch1 axis plays an important role in regulating HG-induced VSMC proliferation and migration.
Preparation of Blueberry Anthocyanin Nanoemulsion And Its Stability and Skin Safety Evaluation
Authors: YIN Mingyue , SONG Jieyu , ZHOU Xiaoling , ZHANG Wei , WU Ao
Published: January 2022

BACKGROUND: Blueberry anthocyanins have strong antioxidant activity, but their instability and low bioavailability limit their use. Nanoemulsion is a new type of food and drug carrier with stable thermodynamic properties. Therefore, anthocyanins will be encapsulated with nanoemulsion to improve its stability and application value.RESULTS: In this study, the best surfactants, oil phases and cosurfactants for the preparation of blueberry anthocyanin nanoemulsion were screened by pseudo-ternary phase diagram method and the solubility of blueberry anthocyanin nanoemulsion was taken into consideration. Deep purplish red, clear and transparent anthocyanin nanoemulsion was prepared by simple and cheap low-energy emulsification method according to the formula. Normal and high temperature test and high speed centrifugal test proved that the blueberry anthocyanin nanoemulsion had good stability. Guinea pig skin irritation test and sensitization test showed that there was no irritation and sensitization to guinea pig hair removal skin. CONCLUSION: The blueberry anthocyanin nanoemulsion prepared in this study has good stability at room temperature and is safe for guinea pig hair removal skin. It provides a basis for improving the stability and bioavailability of blueberry anthocyanin, and provides a reference for the application of blueberry anthocyanin nanoemulsion in skin beauty and transdermal drug delivery.
Effect of Different Preparation Conditions On The Properties of Bamboo Fiber-Based Bioactive Composite Membrane
Authors: Liuyun Jiang , Ma Bingli , Jiang Zhihong , Ma Yingjun , Wen Yue , Zhang Na , Zhang Yan , Su Shengpei , Tang Xionggui , Hu Xiang
Published: January 2022

A novel nano-hydroxyapatite/bamboo fiber (n-HA/BF) bioactive composite membrane was obtained by a simple casting technique. The membrane forming mechanism and the effects of different forming membrane methods, drying methods and n-HA amounts on the properties of n-HA/BF membrane were investigated by Fourier Transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), contact angle, electromechanical universal tester, in vitro soaking in simulated body fluid (SBF) and in vitro cell cultureexperiment. The results demonstrated that the n-HA dispersity in BF matix was not affected by the prepartion condition, however, the morphologies of membrane was determined by the different preparation conditions owing to different hydrogen bond shrinkage. Moreover, the hydrophilicity of the composite membrane was improved under the condition of the membrane formation in oven, freeze drying and high addition content of n-HA, and the mechanical properties of composite membrane depended on n-HA content. In vitro soaking behavior indicated that the degradability and bone-like apatite deposition could be controled by differentpreparation conditions. And the cell proliferation experiment showed that the n-HA/BF composite membranes obtained under different preparation conditions were all non-toxic. The above results indicated that the n-HA/BF composite membrane could be obtained by a simple casting technique, and the properties could be controlled by adopting different preparation conditions, which would have a great promising as guide bone tissue regeneration (GBR) membrane, and the study would provide a new application for BF in biomedical field.
Comparative Proteomics Reveals Differential Mechanism of Root Cold-resistance between Vitis. Riparia × V. Labrusca and Cabernet Sauvignon
Authors: Chen Si-jin , Su Hong-yan , Xing Hua , Yang De-long , Mao Juan , Sun Ping , Li Meng-fei
Published: January 2022

Grapevines, containing large amounts of bioactive metabolites that offer health benefits, are widely cultivated around the world. The cold damage of growing outside with extreme low temperature during overwintering stage limits the expansion of production. Although the levels of morphological, biochemical and molecular in different Vitis species exposure to different temperatures have been investigated, differential expression of proteins in roots is still limited. Here, the roots of cold-resistant (Vitis. riparia × V. labrusca, T1) and cold-sensitive varieties (Cabernet Sauvignon, T3) at −4°C as well as of the former at −15°C (T2) were measured by iTRAQ-based proteomic analysis, expression levels of genes encoding candidate proteins were validated by qRT-PCR. The results showed that the root activity of cold-resistant variety was stronger than that of cold-sensitive variety, and it declined with the decrease of temperature. A total of 25 proteins were differentially co-expressed at T2 versus (vs) T1 and T1 vs T3, and these proteins were involved in stress response (e.g. DHN1, SHSPCP and USPCP), bio-signaling (e.g. PKCP, S/TPP and nsS/TP), metabolism (e.g. GluP, GluBE and PE), energy (e.g. AAC, AAACP and NADCP), and translation (e.g. rpL14, rpS21 and PPI). The relative expression levels of the candidate 13 genes were consistent with their fold-change values of proteins. The signature translation pattern for the roots at spatio-temporal treatments of varieties and temperatures provides insight into the differential mechanism of cold resistance of grapevines.
Gray Matter Atrophy And Corresponding Impairments In Connectivity In Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Authors: Guo Yuanyuan , Lv Xinyi , Zhang Juanjuan , Li Chenglong , Wei Ling , Zhou Nong , Xu Jinping , Tian Yanghua , Wang Kai
Published: January 2022

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disease that is commonly accompanied by cognitive impairment and various neurological and psychiatric symptoms, advanced image analyses help explore the pathogenesis of this disease. Therefore, this study aimed to explore specific structural and functional alterations and their relationship with the clinical symptoms of anti-NMDAR encephalitis. In this study, twenty-two patients with anti-NMDAR encephalitis after the acute stage and 29 controls received cognitive assessments and magnetic resonance imaging. Grey matter atrophy was measured using voxel-based morphometry, and functional alterations in abnormal regions were subsequently investigated using resting state functional connectivity (RSFC). Finally, correlation analyses were performed to explore the associations between imaging alterations and cognitive assessments. The patients demonstrated significant gray matter atrophy in the bilateral triangle part of the inferior frontal gyrus (triIFG.L and triIFG.R) and right precuneus, decreased RSFC between triIFG.L and bilateral Heschl gyrus (HES), decreased RSFC between triIFG.R and HES.R, decreased RSFC between right precuneus and left cerebellum, and increased RSFC between triIFG.R and left superior frontal gyrus. Further correlation analyses showed that the gray matter volume in triIFG.R and decreased RSFC between triIFG.L and HES.R were associated with decreased memory scores, whereas decreased RSFC between triIFG.R and HES.R was marginally correlated with the disease course in patients. In conclusion, this study suggests that cognitive impairments in patients with anti-NMDAR encephalitis may be mainly associated with gray matter atrophy and abnormal RSFC in the triIFG. These findings provide new insights into anti-NMDAR encephalitis pathogenesis and help explore potential treatments.
Prognostic Value of Tumor-stroma Ratio in Oral Squamous Cell Carcinoma: Contribution of Cancer Associated Fibroblasts
Authors: Qiu Jingjian , Jiang Erhui , Shang Zhengjun
Published: January 2022

Background: The aim of this study is to confirm the prognostic value of the tumor–stroma ratio (TSR) in a large cohort of oral squamous cell carcinoma (OSCC) and further demonstrated the cancer associated fibroblasts (CAFs)-stroma ratio (CSR) served as a critical biomarkers contributed to the prognostic value of TSR Results: The threshold level of TSR value is 50%, which divides patients into high (>50%) and low (<50%) stroma. We examined the TSR on hematoxylin and eosin-stained tissue samples from 581 patients with oral squamous cell carcinoma and 298 cases were included in the high-stroma group. In multivariate analysis, the TSR was identified as an independent prognostic factor for disease-free survival (DFS) (hazard ratio (HR), 2.11; 95% confidence interval (CI), 1.56–2.86; p < 0.001) and oral cancer-specific survival (OCSS) (HR, 2.56, 95% CI, 1.78–3.67; p < 0.001). The interaction term reached statistical significance for histological grade. Multivariate analysis confirmed the discriminative value of the TSR in well differentiated tumors for DFS and OCSS separately (P=0.001, P=0.003). The prognostic value of TSR was not varied by other clinically subgroups. Furthermore, the high-stroma group had a higher Fibroblast Activation Protein (FAP+) CSR and α-Smooth Muscle Actin (α-SMA+) CSR than the low-stroma group (p < 0.001).Conclusion: High-stroma levels indicated a negative consequence and a higher CAFs–stroma ratio than low-stroma levels in OSCC. The TSR is not altered by other clinically elements rendering it a credible histological parameter and informing the rational design of individual cancer management.
Silent Death by Sound: C60 Fullerene Sonodynamic Treatment of Cancer Cells
Authors: Radivoievych Aleksandar , Kolp Benjamin , Grebinyk Sergii , Prylutska Svitlana , Ritter Uwe , Zolk Oliver , Glökler Jörn , Frohme Marcus , Grebinyk Anna
Published: January 2022

The acoustic pressure waves of ultrasound (US) penetrate biological tissues deeper than light. Another important feature of US its potential to generate light emission within the excited medium termed sonoluminescence. This promoted the idea of its use as an alternative energy source for photosensitizer excitation. Pristine C60 fullerene (C60), an excellent photosensitizer, was explored in the frame of cancer sonodynamic therapy (SDT). For that purpose, we analyzed C60 effects on human cervix carcinoma HeLa cells in combination with a low intensity US treatment. The time-dependent accumulation of C60 in HeLa cells reached its maximum at 24 h (800 ± 66 ng / 106 cells). Half of extranuclear C60 localized within mitochondria. The efficiency of C60 nanostructure’s sonoexcitation with 1 MHz US was tested with cell viability assay. A significant proapoptotic sonotoxic effect was found for HeLa cells. C60’s ability to induce apoptosis of carcinoma cells after sonoexcitation with US provides a promising novel approach for cancer treatment.
Extracellular Vesicles from Carcinoma-Associated Fibroblasts Promote Epithelial-Mesenchymal Transition of Salivary Adenoid Cystic Carcinoma via Interleukin-6
Authors: Kong Jing , Ran Yan , Zhu Lei , Li Jiao , Liu Xue , Yang Xuesong , Qi Dongyuan , Liu Tingjiao
Published: January 2022

Carcinoma-associated fibroblasts (CAF) play a pivotal role in cancer progression. Salivary adenoid cystic carcinoma (SACC) has a high tendency to invade and metastasize. Understanding how CAF interact with SACC cells is essential to develop new targeting therapies for SACC. Extracellular vesicles (EVs) play important roles in intercellular communication. However, the role of CAF-derived EVs in SACC invasion remains poorly understood. In this study, we show that CAF EVs promote the migration and invasion abilities of SACC cells. The expression of biomarkers of epithelial-mesenchymal transition (EMT) was higher in SACC cells treated with CAF EVs treated with CAF EVs than in the negative controls, and high levels of IL-6 were detected in CAF and their EVs. Knockdown of IL-6 in CAF decreased invasive abilities and EMT biomarker expression in SACC cells induced by CAF EVs. CAF EV-associated IL6 promoted SACC EMT by activating JAK2/STAT3 signaling pathway. These findings suggest that targeting CAF-derived EVs may be an effective strategy for inhibiting SACC invasion.
A New Chemical-Mechanical Polishing Method Based On Colloids Silica and MgO Was Developed For Polishing Y3Al5O12 Material
Authors: Duc Le Anh , Hieu Pham Minh , Quang Nguyen Minh
Published: January 2022

The material yttrium aluminum oxide (Y3Al5O12) is one of the materials commonly used in laser devices. For application in optical devices, it is necessary to produce ultra-precise surface quality, however, Y3Al5O12 material belongs to the group of difficult-to-machine materials with high brittleness and hardness. Therefore, it is very difficult to ensure that the main criterion when finishing this material to produce a quality surface in the nanometer form with the ability to remove the material is very difficult. To solve this problem, this work provided a new chemical - mechanical polishing mixture. The proposed polishing mixture of ZrO2, Na2SiO3–5H2O, and MgO abrasives has a weight ratio of 8%, 5% and 1% respectively, with the remainder being deionized water. The surface result after polishing is obtained with a material removed rate of 38 (nm/min) along with an ultra-smooth surface produced with Ra = 0.41 nm. With the help of X-ray photoelectron spectroscopy (XPS) method before and after polishing by CMS, the reaction mechanisms were elucidated. Analytical results show that Y3Al5O12 material produces YOOH and AlOOH in Na2SiO3 solution, then combines with –Si–OH to form (Y-Si) and (Al-Si) with significantly reduced hardness compared to other Y3Al5O12 materials, these products combine with MgO to form montmorillonites (3MgO–Al2O3–3SiO2–3Y2O3–5Al2O3). With this formation, the surface layer of Y3Al5O12 material becomes soft and is easily removed by ZrO2 abrasive particles under the influence of mechanical polishing, resulting in superfine surfaces are generated from the proposed CMS model.
Study The Mechanism of Huangdi Anxiao Capsules In The Treatment of T2DM of Using UPLC-Q-TOF-MSE Combined With Network Pharmacological
Authors: Zhang Wei , Shan Li , Zhu Meng Qing , Fang Zhao Hui , Liu Xiao Chuang , Gao Jia Rong
Published: January 2022

This study was to explore the main material basis, target and pathway of Huangdi Anxiao capsule (HDAXC) for the treatment of type 2 diabetes mellitus (T2DM) by UPLC-Q-TOF-MSE and network pharmacology. In this study, HDAXC was administrated to T2DM rats, and its serum were detected by UPLC- Q-TOF-MSE, and the prototype components of HDAXC were analyzed. Using Swiss target prediction database to predict the target of serum prototype components, using GeneCards and DrugBack database to predict the target of T2DM. These common targets are the prediction target of HDAXC acting on T2DM. The key components of HDAXC in the treatment of T2DM were determined by using the software of Cytoscape3.7.2 to visualize the results. Using the STRING online platform to construct the protein-protein interaction (PPI), the key target genes were selected. The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the common targets were carried out by using the OmicShare tools. And quantitative PCR and Western bolt were used to verify the related target genes. A toll of 28 prototype compounds were detected in rat serum, and 495 putative identified target genes were screened from HDAXC, of which 141 overlapped with the targets of T2DM and were considered potential therapeutic targets. The analysis of the network results showed that the key components of HDAXC are Magnoflorine, Galangin, Quercetin, and Epiberberine, etc. VEGFA, AKT1, SRC, EGFR might be the key target genes of HDAXC in the treatment of T2DM. HDAXC may have a therapeutic effect on T2DM by affecting HIF-1 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, VEGFA signaling pathway and PI3K/AKT signaling pathways. In this study, compounds absorbed into the blood of HDAXC and its action target and pathway were preliminarily analyzed, which provided evidences for clarifying the chemical material basis and researching functional mechanism of HDAXC.
The Grapefruit Flavonoid Naringenin Inhibits Multiple Cardiac Ion Channels
Authors: Sanson Camille , Boukaiba Rachid , Houtmann Sylvie , Maizières Magali-Anne , Fouconnier Sophie , Partiseti Michel , Bohme Georg Andrees
Published: January 2022

Drinking fresh grapefruit juice is associated with a significant prolongation of the QT segment on the electrocardiogram (ECG) in healthy volunteers. Among the prominent flavonoids contained in citrus fruits, the flavanone naringenin is known to be a blocker of the human ether-a-go-go related gene (hERG) potassium channel. We hypothesized that naringenin could interfere with other major ion channels shaping the cardiac ventricular action potential (AP). To this end, we examined the effects of naringenin on the seven currents comprising the Comprehensive in vitro Pro-Arrhythmia (CiPA) panel for early arrhythmogenic risk assessment in drug discovery and development. We used automated patch-clamp of human ion channels heterologously expressed in mammalian cell lines to evaluate half-maximal inhibitory concentrations (IC50). Naringenin blocked all CiPA currents tested with IC50 values in the 30 µM – 100 µM concentration-range. The rank-order of channel sensitivity was the following: hERG > Kir2.1 > NaV1.5 late > NaV1.5 peak > KV7.1 > KV4.3 > CaV1.2. This multichannel inhibitory profile of naringenin suggests exercising caution when large amounts of grapefruit juice or other citrus juices enriched in this flavanone are drunk in conjunction with QT prolonging drugs or by carriers of congenital long QT syndromes.
Relationship Between 18F-fluorodeoxyglucose Uptake on Positron Emission Tomography and Aortic Calcification
Authors: Okamura Yuriko , Nakanishi Rine , Hashimoto Hidenobu , Ota Kyoko , Okubo Ryo , Yabe Takayuki , Noike Ryota , Mizumura Sunao , Kishi Kazuma , Homma Sakae , Ikeda Takanori
Published: January 2022

IntroductionAlthough 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been widely utilized to assess the extent of inflammation, the association between the extent and severity of atherosclerosis and 18F-FDG uptake on PET remains unexamined. The current study aimed to investigate whether aortic calcium (AC) scores were associated with increased aortic uptake of 18F-FDG on PET.MethodsA total of 167 consecutive patients with suspected lung cancer but unproven malignancy who underwent non-contrast-enhanced computed tomography (CT) and 18F-FDG PET/CT were enrolled. The average standardized uptake values in the ascending aorta was used to calculate the target-to-background ratio (Mean TBR). The total (thoracic and abdominal) AC scores were measured on non-contrast-enhanced chest and abdominal CT using the Agatston method, and were categorized into three groups (0, 1–399, and ≥400). The relationship between total AC scores and 18F-FDG uptake in the ascending aorta was assessed using multivariate linear regression analysis.　ResultsIn total, 68.26% were male, and a mean age was 67.10±14.70 years. Mean TBR values increased progressively with total AC score 0, 1–399, and ≥400 (1.01±0.07, 1.08±0.09, and 1.11±0.11, respectively; p<0.00001). Multivariate linear regression analysis revealed that increased total AC scores of 1–399 (β=0.06, 95% CI: 0.01–0.11, p=0.02) and ≥400 (β=0.11, 95% CI: 0.06–0.16, p<0.001) were significantly associated with higher Mean TBR. ConclusionsThe current study demonstrated that total AC scores were associated with Mean TBR. Patients with a greater extent and severity of aortic calcifications may possess increased atherosclerotic inflammatory activity as measured by 18F-FDG PET/CT.
Metabolic and Texture Features of PET/CT Scan to Predict Response in Patients with Locally Advanced Rectal Cancer Treated by Concurrent Neoadjuvant Chemoradiotherapy
Authors: aarabi mhsen , shayesteh sajad pashutan , Alikhassi Afsaneh , Esfahani Armaghan Fard , Geramifar Parham , Bitarafan-Rajabi Ahmad
Published: January 2022

Background: Neoadjuvant chemoradiotherapy (nCRT) before surgical resection is the standard treatment for patients with locally advanced rectal cancer (LARC). Radiomics can be used as noninvasive biomarker for response prediction. The purpose of our study was to evaluate the potential of PET/CT texture features to predict the responses of LARC subjects treated with nCRT.Methods: One week prior to nCRT, patients underwent Positron Emission Tomography/Computed Tomography (PET/CT) scan and then received concurrent nCRT. For each patient, intensity, shape and texture-based features were derived from PET/CT images using the IBEX software. The logistic regression classifier was used to identify the responders from non-responders. Results: In this study, 23 patients with LARC were included. The patients’ responses included 5 patients with Grade 0, 7 with Grade 1, 6 with Grade 2, and 5 with Grade 3 according to American Joint Committee on Cancer/College of American Pathologists (AJCC/CAP) pathologic grading. In quantitative texture features analysis, the dissimilarity feature had the highest performance [Area under Curve (AUC) = 0.65] and in metabolic parameters analysis the best performance was for total lesion glycolysis (TLG; AUC= 0.61)Conclusions: In conclusion, performance of quantitative texture features is better than metabolic parameters but their performance should be improved.
Multi-year Use of the Standard Gauge Railway Underpasses by Mammals in Tsavo, Kenya: Influence of Underpass Dimensions, Infrastructure and Ecology
Authors: Lala Fredrick , Chiyo Patrick I. , Omondi Patrick , Okita-Ouma Benson , Kanga Erustus , Koskei Michael , Tiller Lydia , Morris Aaron W. , Bump Joseph K.
Published: January 2022

Rail and road infrastructure is essential for economic growth and development but can cause a gradual loss in biodiversity and degradation of ecosystem function and services. We assessed influence of underpass dimensions, fencing, proximity to water and roads, Normalized Difference Vegetation Index (NDVI), presence of other species and livestock on underpass use by large and medium-sized mammals. Results revealed hyenas and leopards used the underpasses more than expected whereas giraffes and antelopes used the underpasses less than expected. Generalized linear mixed effects models (GLMMs) revealed that underpass height influenced their use by wildlife, with several species preferring to use taller underpasses. Electric fencing increased underpass use by funneling species towards underpasses, except for elephants and black-backed jackal for which it reduced underpass passage. GLMMs also revealed that the use of underpasses by livestock reduced the probability of their use by nearly 50% of wildlife species. Carnivore species were more likely to cross underpasses used by their prey. Buffalo, livestock, and hyenas used underpasses with higher NDVI and near water sources while baboons, dik-diks and antelope avoided underpasses with high NDVI. The findings suggest a need for diverse, and comprehensive approach for mitigating the negative impacts of rail on African wildlife.
TRPM8 Deficiency Attenuates Liver Fibrosis Through S100A9-HNF4α Signaling
Authors: Liu Qiang , Lei Xiaohua , Cao Zhenyu , Zhang Ju , Yan Likun , Fu Jie , Tong Qing , Qin Wei , Shao Yaoli , Liu Chun , Liu Zhiqiang , Wang Zicheng , Chu Yuan , Xu Ge , Liu Siyuan , Wen Xueyi , Yamamoto Hirofumi , Mori Masaki , Liang Xin. M. , Xu Xundi
Published: January 2022

Background

Liver fibrosis represent a major global health care burden. Data emerging from recent advances have suggested TRPM8, a member of the transient receptor potential (TRP) family of ion channels, plays an essential role in various chronic inflammatory diseases. However, its role in liver fibrosis remains unknown. Herein, we assessed the potential effect of TRPM8 in liver fibrosis.
Methods

The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8−/− (KO) fibrotic mice after carbon tetrachloride (CCl4) or bile duct ligation (BDL) treatment. The role of TRPM8 was systematically evaluated using specimens obtained from the aforementioned animal models after various in vivo and in vitro experiments.
Results

Clinicopathological analysis has shown TRPM8 expression was upregulated in tissue samples from cirrhosis patients and fibrotic mice. TRPM8 deficiency not only attenuated inflammation and fibrosis progression in mice, but also helped to alleviate symptoms of cholangiopathies. Moreover, reduction in S100A9 and increase in HNF4α expressions were observed in liver of CCl4 and BDL treated TRPM8 KO mice. Strong regulatory linkage between S100A9 and HNF4α was also noticed in L02 cells underwent siRNA-mediated S100A9 knockdown and S100A9 overexpressing plasmid transfection. Lastly, alleviative effect of a selective TRPM8 antagonist was confirmed in vivo.
Conclusion

These findings suggest TRPM8 deficiency may exert protective effects against inflammation, cholangiopathies and fibrosis through S100A9-HNF4α signaling mechanistically. M8-B might be a promising therapeutic candidate for liver fibrosis.
Do Leonardo Da Vinci’s Drawings, Room Acoustics And Radio Astronomy Have Anything In Common?
Authors: Kulowski Andrzej
Published: January 2022

After introducing Leonardo da Vinci’s (LdV) predecessors in the field of light propagation research, his drawings on the topic of focussing light through a spherical mirror are analysed. The discovery of LdV is presented, according to which, at an infinitely distant source of rays, a small fragment of the canopy is enough to generate a focus, while the rest of the mirror forms caustics for which LdV did not indicate an application. An analytical description of the energy concentration in the focus and on the caustics is given, together with its reference to the geometric representation of the acoustic field in rooms. Using symmetry in the description of energy relations in acoustics and electromagnetism, the interference that occurs on the caustics produced by the acoustic and electromagnetic wave is discussed. It is explained why in the sound field in existing halls, instead of a whole caustic only its cusp is observed, which is perceived as a point-like sound focus. The size of the mirror aperture, shown graphically by LdV, is determined. How the development of receiving techniques increased the mirror aperture compared to the LdV estimate is also shown. The implementation of these improvements is presented via the example of the Arecibo and FAST radio telescopes.
Smaller Amygdala Subnuclei Volume in Schizophrenia Patients with Violent Behaviors
Authors: Hu Hao , Liu Fengju , Liu Li , Mei Yi , Xie Bin , Shao Yang , Qiao Yi
Published: January 2022

Objective

To investigate the association between the volume of amygdala subnuclei and violent behaviors in patients with schizophrenia (SCZ).
Methods

In the present study, we recruited 40 SCZ patients with violent behaviors (VS), 26 SCZ patients without violent behaviors (NVS), and 28 matched healthy controls (HC) who completed T1-weighted magnetic resonance imaging. Both the total amygdala and amygdala subnuclei volumes were estimated with FreeSurfer.
Results

When comparing the whole SCZ patients with HC, SCZ patients had smaller volume of the left amygdala and the left basal nucleus. Further, the VS patients had smaller volume of the amygdala central nucleus as compared to the NVS group.
Conclusions

Our findings suggested that a smaller volume of the amygdala central nucleus might be relevant to violence risk in SCZ patients.
N6-Methyladenosine Regulatory Machinery is Involved In Viral Infection of Plum Pox Virus And Potato Virus Y In Nicotiana Benthamiana
Authors: Yue Jianying , Wei Yao , Chen Yahan , Wei Xuefeng , Wang Haijuan , Zhao Mingmin
Published: January 2022

The authors have requested that this preprint be removed from Research Square.
Logic-in-Memory Inverter Based on a Silicon Nanowire Feedback Field-Effect Transistor
Authors: Baek Eunwoo , Son Jaemin , Cho Kyoungah , Kim Sangsig
Published: January 2022

In this paper, we propose a logic-in-memory (LIM) inverter comprising a silicon nanowire (SiNW) n-channel feedback field-effect transistor (n-FBFET) and a SiNW p-channel metal oxide semiconductor field-effect transistor (p-MOSFET). Further, we investigated the hybrid logic and memory operations of the inverter using mixed-mode technology computer-aided design simulations. Our LIM inverter exhibited a high voltage gain of 296.8 (V/V) when transitioning from logic ‘1’ to ‘0’ and 7.9 (V/V) when transitioning from logic ‘0’ to ‘1’, while holding calculated logic at zero input voltage. The energy band diagrams of the n-FBFET structure demonstrated that the holding operation of the inverter was implemented by controlling the positive feedback loop. Moreover, the output logic can remain constant without any supply voltage, resulting in zero static power consumption.
Long Noncoding RNA MIR210HG is Induced by Hypoxia-inducible Factor 1α and Promotes Cervical Cancer Progression
Authors: Hu Xiao-lin , Huang Xia-tong , Zhang Jia-ni , Liu Jie , Wen Li-jun , Xu Xin , Zhou Jue-yu
Published: January 2022

Background：Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play essential roles in various types of cancer, especially the ability of tumor cells to adapt to hypoxia conditions. However, only a few of them have been experimentally validated in cervical squamous cell carcinoma (CSCC). Method: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to confirm the expression of MIR210HG in CSCC tissues compared with matched non-tumor tissues, and analyze its clinical significance. In vitro, RNA interference (siRNA) or overexpression plasmid was used to investigate the biological function and underlying mechanism of MIR210HG in cervical carcinogenesis. In vitro, cell proliferation and metastasis were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Furthermore, tumor growth and metastasis were evaluated in vivo using a xenogenous subcutaneously implant or a pulmonary metastasis model. Immunohistochemical staining or immunoblotting analysis was carried out to detect protein expression.Results：In the current study, we identified a hypoxia-induced lncRNA MIR210HG was excessively expressed in CSCC tissues and regulated by human papillomavirus (HPV) type 16 E6 and E7 via hypoxia-inducible factor 1α (HIF-1α). Functional assays revealed the role of MIR210HG in promoting proliferation, migration and invasion of CSCC cells in vitro under normoxia as well as hypoxia conditions. Meanwhile, stable MIR210HG silencing dramatically repressed tumor growth and pulmonary metastasis in vivo. Mechanistically, the depletion of MIR210HG or HIF-1α decreased each other’s expression level, while silencing MIR210HG or HIF-1α respectively downregulated the expression levels of phosphoglycerate kinase 1 (PGK1), one of key metabolic enzymes in the glycolysis pathway. Furthermore, decreased expression of PGK1 by HIF-1α knockdown was reversed through the overexpression of MIR210HG. Also, we demonstrated HIF-1α can activate the transcription of MIR210HG via binding its promoter. Conclusions: Taken together, these results expand our understanding of the cancer-associated functions of hypoxia-induced lncRNAs, and highlight MIR210HG forms a feedback loop with HIF-1α contributing to cervical carcinogenesis, with potential implications for therapeutic targeting.
Association Between Timing of Speech and Language Therapy Initiation and Outcomes Among Post-Extubation Dysphagia Patients: A Multicenter Retrospective Cohort Study
Authors: Hongo Takashi , Yamamoto Ryohei , Liu Keibun , Yaguchi Takahiko , Dote Hisashi , Saito Ryusuke , Masuyama Tomoyuki , Nakatsuka Kosuke , Watanabe Shinichi , Kanaya Takahiro , Yamaguchi Tomoya , Yumoto Tetsuya , Naito Hiromichi , Nakao Atsunori
Published: January 2022

Background: Post-extubation dysphagia (PED) is recognized as a common complication in the intensive care unit (ICU). Speech and language therapy (SLT) can potentially help improve PED; however, the impact of the timing of SLT initiation on persistent PED has not been well investigated. This study aimed to examine the timing of SLT initiation and its effect on patient outcomes after extubation in the ICU.Methods: We conducted this multicenter, retrospective, cohort study, collecting data from eight ICUs in Japan from patients treated between 2017 and 2020. Patients aged ≥ 20 years with orotracheal intubation and mechanical ventilation for longer than 48 hours, and those who received SLT due to PED, defined as patients with modified water swallowing test scores of 3 or lower, were included. The primary outcome was dysphagia at hospital discharge, defined as functional oral intake scale score <5 or death after extubation. Secondary outcomes included dysphagia or death at the seventh, 14th, or 28th day after extubation, aspiration pneumonia, and in-hospital mortality. Associations between the timing of SLT initiation and outcomes were determined using multivariable logistic regression. Results: Two hundred and seventy-two patients met the study inclusion criteria. Of them, 82 (30.1%) patients exhibited dysphagia or death at hospital discharge, and their time spans from extubation to SLT initiation was 1.0 days. The primary outcome revealed that every day of delay in SLT initiation post-extubation was associated with dysphagia or death at hospital discharge (adjusted odds ratio (AOR), 1.09; 95% CI, 1.02 to 1.18). Similarly, secondary outcomes showed associations between this per day delay in SLT initiation and dysphagia or death at the seventh day (AOR, 1.28; 95% CI, 1.05 to 1.55), 14th day (AOR, 1.34; 95% CI, 1.13 to 1.58), or 28th day (AOR, 1.21; 95% CI, 1.07 to 1.36) after extubation and occurrence of aspiration pneumonia (AOR, 1.09; 95% CI, 1.02 to 1.17), while per day delay in post-extubation SLT initiation did not affect in-hospital mortality (AOR, 1.04; 95% CI, 0.97 to 1.12). Conclusions: Delayed initiation of SLT in PED patients was associated with persistent dysphagia or death. Early initiation of SLT may prevent this complication post-extubation.
Precipitation of Sugammadex With Nicardipine And Labetalol
Authors: Han Jiwon , Oh Ah-Young , Kim Bo Young
Published: January 2022

BackgroundThere is a paucity of clinical data about whether sugammadex forms precipitates with other medications. This laboratory experimental study was performed to determine the drugs that produce precipitate with sugammadex. MethodsSamples of 1 mL of sugammadex were prepared in transparent cylinders, to which 1 mL of test drugs (rocuronium, neostigmine, glycopyrrolate, atropine, nitroglycerin, dobutamine, dopamine, epinephrine, vasopressin, norepinephrine, phenylephrine, ephedrine, esmolol, nicardipine, labetalol) was then added. The precipitation reaction was observed by eyes and light microscope. The pH of each drugs before and after mixing with sugammadex was measured. ResultsWhite crystals were formed when sugammadex mixed with nicardipine or labetalol. ConclusionsSugammadex formed precipitate when mixed with nicardipine or labetalol. Sufficient fluid flushing is required between injections of each drug to prevent these reactions.
Erythropoietin Receptor is a Risk Factor for Prognosis: A Potential Biomarker in Lung Adenocarcinoma
Authors: Zhang Ya-Jing , Wang Sen-Yu , Han Song-Tao , Huang Yao-Yao , Feng Yang-Chun
Published: January 2022

Background: Lung cancer has the highest mortality rate of all cancers, and LUAD's survival rate is particularly poor. Erythropoietin receptor (EPOR) is a member of the cytokine class I receptor family and can be detected in cancers such as lung adenocarcinoma (LUAD), however, the expression levels and prognostic value of EPOR in LUAD are still unclear.Methods: Multiple bioinformatics databases such as TIMER, Kaplan-Meier Plotter and TCGA databases, immunohistochemical method, and clinicopathological data of 92 LUADpatients between January 2008 and June 2016 were used to explore the EPOR expression, gene mutations affecting EPOR expression, EPOR-interacting or coexpressed genes, potential biological functions and the correlation of EPOR expression with prognosis, immune microenvironment and so on.All statistical analyses were performed in the R version 4.1.1.Results: In this study, the EPOR mRNA expression in LUAD tissues was possibly downregulated compared with that in normal lung tissues, but the EPOR protein expression in LUAD tissues was higher than that in paired normal lung tissues. Mutations in five genes, DDX60L, LGR6, POTEB3, RIF1 and SOX5, resulted in downregulation of EPOR expression, mutations in 10 genes includingC1orf168, DBX2 and EIF5B, resulted in upregulation of EPOR expression. Erichment analyses showed that EPOR is involved in neural tissue ligand-receptor interactions, MAPK and PI3K/Akt signaling pathways and cancer pathways. The KM Plotter and PrognoScan databases consistently concluded that EPOR was associated with prognosis in LUAD patients. Our clinicopathological data showed that high EPOR expression was associated with poorer OS (29.5 vs 46 months) and had a good predictive ability for 5-year survival probability. Conclusions: EPOR expression might be downregulated at the mRNA levels and significantly upregulated at the protein levels in LUAD, which showed that the mRNA and protein levels of EPOR are inconsistent.The high expression of EPOR was associated with poor prognosis and is expected to be a potential new prognostic marker for LUAD.
Clinical Application of a Modified Bone Cement Pusher in Percutaneous Vertebroplasty Combined with Multi-Target Negative Pressure Rotary-Cutting Technique in Puncture Biopsy for Bone Tumors
Authors: Yang Zongqiang , Tang Jing , Ma Hongbao , Wang Linan , Shi Jiandang , Niu Ningkui
Published: January 2022

Purpose To assess the efficiency and safety of a modified bone cement pusher in percutaneous vertebroplasty (PVP) combined with a multi-target negative pressure rotary-cutting technique in puncture biopsy of bone tumors. Methods The biopsy performed with the modified bone cement pusher commonly used in PVP, and a multi-target negative pressure rotary-cutting technique. A total of 120 patients with spinal and pelvic tumors undergoing needle biopsy in our department were recruited and assigned to new biopsy device group (group A, n=60) or and conventional biopsy device group (group B, n=60). The puncture time, positive rate, consistency rate, and dependence rate between group A and B were compared to assess the efficiency and safety of the new device. Results No biopsy-related complications were reported in both groups. The puncture time (39.44±8.885 min vs. 61.61±9.880 min), positive rate (96.67% vs. 61.67%), consistency rate (96.55% vs. 81.8%), and dependence rate (100% vs. 83.33%) were significantly superb in group A compared with those in group B (all P<0.05). Patients in group A did not require repeated biopsies, and sufficient samples were obtained through the needle trajectory in PVP. All patients with a definite diagnosis were managed with appropriate treatments. Conclusions Featuring high safety, positive rate and consistency rate, the new device can be performed to collect sufficient pathological samples from multiple angles. Wide clinical replication can be expected considering its evident diagnostic efficiency for bone tumor.
Observational Study: Application of Therapy with Equine Serum for Patients Diagnosed with COVID-19 in Tucumán, Argentina
Authors: Chahla Rossana Elena , Ruiz Luis Medina , Contreras Miguel Enrique Ferré , Raya Mario , MsC Natalia Herrera , Ortega Eugenia Silvana , Gustavo Daniel Gustavo Goroso , de Bruno María de los  Ángeles Peral
Published: January 2022

Purpose: The objective of this work is to make an observational study of the usage in moderate or severe state COVID-19 patients of a new therapeutic commercial product obtained after immunization of horses: CoviFab® ELEA F(ab')2 fragmented equine immunoglobulins anti SARS-CoV2.Methods: Participant Centres depend on the Public Health System of Tucumán, Argentina were recruitment. Subjects were assigned to the Moderate Patient Group (MPG) and the Severe Patient Group (SPG), classified according to WHO criteria.In total, n = 84 were enrolled for this study. The subjects were divided into MPG and SPG. All participants were evaluated by physical examination and COVID-19 infection was diagnosed with positive RT-PCR. Each subject received two doses of 0.16 ml / kg, according to the subject's body weight. A generalized linear model with binomial distribution was adjusted for the number of symptoms. Data was analysed using proportion, bivariate and logistic regression. P-value was considered significant at the p< 0.05 threshold.Results: Both groups were similar in age, sex, and comorbidities. A higher proportion of patient with medical discharge was observed in MPG (91.4%) vs. SPG (55.3%) (p= 0.004). MPG showed 9 times more chance of receiving medical discharge than SPG (9.33 CI= [1.65, 52.81]; p= 0.012). Then, the chance to get medical discharge was independent of variables sex, age, and comorbidities. Conclusions: Treatment with Equine Serum in patients with moderate and severe disease of COVID-19 managed to slightly reduce hospitalization time. This treatment improved the clinical state to obtain medical discharge. The bivariate analysis showed 8 times more chance in MGP versus SGP to receive of medical discharge and this chance was independent of the pre-existent comorbidities.
A Dual/Single Wideband Switchable Metamaterial Absorber at Low Frequency
Authors: Wang Liansheng , Xia Dongyan , Fu Quanhong , Ding Xueyong , Wang Yuan
Published: January 2022

Based on PIN diode and resistive film, a dual/single wideband switchable metamaterial absorber at low frequency is presented in this paper. Its absorption is over 90% from 0.8GHz to 1.5GHz and from 4.2GHz to 5.2GHz while the PIN diode operates in forward biased condition. On the contrary, with the PIN diode acting in reverse biased condition, the above 90% absorption occurs from 1.1GHz to 3.2GHz. The surface current distributions at the absorption frequencies are monitored to explain the reason of wideband absorption. The simulation results show that the absorption property of the metamaterial absorber is polarization-sensitive. The metamaterial absorber possesses the advantages of simple structure, wideband, dual/single band, and switchable performance.