bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological potential of silver nanoparticles synthesized by an endophytic fungus Metapochonia suchlasporia-KUMBMDBT-23
Authors: D Manjunatha , S Akarsh , G Nandish , H.V Sowmya , G.T Megha , S Nagaraju , B Thippeswamy
Published: December 2022

In this study, we demonstrated a simple, green, and eco-friendly method for the synthesis of silver nanoparticles using the endophytic fungus Metapochonia suchlasporia-KUMBMDBT-23 isolated from the medicinal plant Argemone mexicana. Silver nanoparticles were synthesised using the biomass cell filtrate of Metapochonia suchlasporia, which was identified by morphological and molecular characterization. The fungus extract was extracted with ethyl acetate (1:1 V/V) and was analysed by GC-MS. Biosynthesized silver nanoparticles were investigated by Bio-spectrophotometer, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy – Energy Dispersive Analysis of X-ray, (SEM-EDAX), X-ray diffraction (XRD) and Particle size analysis by dynamic light scattering (DLS). Metapochonia suchlasporia synthesised silver nanoparticles were effective against gram-positive and gram-negative human pathogenic bacteria. Using market antibiotics, the antimicrobial enhancing activity and minimum inhibitory concentration of silver nanoparticles was evaluated. The antifungal activity of silver nanoparticles against fungal infections was determined. Moreover, silver nanoparticles synthesised showed effect of DPPH and ABTS scavenging activities. Further in -vitro anticancer activity was determined by MTT assay using HePG2 and A498 cell lines. In -vitro anti-inflammatory activity was determined by egg albumin, bovine serum albumin denaturation test and membrane stabilization test, HRBC, in- vivo anti-inflammatory activity was determined by inducing Female Swiss Albino mice with inflammatory agent’s carrageenan paw edema. This study showed silver nanoparticles generated by microbes are effective inhibitors and have potential biological implications.
Effect of waste concrete powder on concrete properties and microscopic mechanism analysis
Authors: Li Te , Tier Laire
Published: December 2022

With the rapid development of urban urbanization, a large number of old buildings that do not meet the urban construction planning have been demolished, and a large number of buildings left a lot of construction waste. The direct waste of construction waste is not only a large waste of sand and cement resources, but also increases the production cost of construction enterprises. The slump and rheology tests show that the addition of waste concrete powder is unfavorable to the working performance of concrete. The rheology shows that the waste concrete powder leads to the increase of friction force and the decrease of slump. With the increase of substitution rate, the compressive strength decreases. ICP shows that the dissolution of early concrete powder is involved in hydration. Nanoindentation shows that the hydration products change. In addition, because the waste concrete powder is rich in Si, the hydration product Si / Ca increases. In addition, MIP and UPV results show that the durability of concrete with concrete powder becomes worse. Since the concrete powder also needs to be calcined and ground, although there is still more CO2 emissions, there is still a slight decrease compared with cement. Therefore, with the increase of the substitution rate, certain economic and environmental benefits can be obtained.
A breakdown of metabolic reprogramming in microglia caused by CKLF1 exacerbates immune tolerance in the ischemic stroke
Authors: Ma Wenyu , Wu Qinglin , Wang Shasha , Wang Hongyun , Ye Junrui , Sun Hongsuo , Feng Zhongping , He Wenbin , Chu Shifeng , Zhang Zhao , Chen Naihong
Published: December 2022

Ischemic stroke has a prominent pathogenic hallmark called reactive microglia, which is a predictor of prognosis. The precise involvement of microglia in stroke etiology, however, is still unknown. We found that chemokine like factor 1 (CKLF1) causes acute microglial inflammation and metabolic reprogramming from oxidative phosphorylation to glycolysis utilizing metabolic profiling, which was reliant on the AMPK-mTOR-HIF-1α signaling pathway. Microglia, once activated, entered a chronic tolerant state as a result of widespread energy metabolism abnormalities and therefore reduced immunological responses, including cytokine release and phagocytosis. It was also found metabolically dysfunctional microglia in the mice using genome-wide RNA sequencing by chronic administration of CKLF1 directly, as well as the decrease of inflammation response. Finally, we showed that loss of CKLF1 reversed the defective immune response of microglia, as manifested by kept its phagocytosis to neutrophils, thereby mitigating long term outcomes of ischemic stroke. Overall, CKLF1 plays a crucial part in the relationship between microglial metabolic status and immune function in stroke, which prepares a potential therapeutic strategy for ischemic stroke.
Anisotropy in Multiferroic CuCrP2S6
Authors: Wang Xiaolei , Shang Zixuan , Zhang Chen , Kang Jiaqian , Liu Tao , Wang Xueyun , Chen Siliang , Liu Haoliang , Tang Wei , Zeng Yu-Jia , Guo Jianfeng , Cheng Zhihai , Liu Lei , Pan Dong , Tong Shucheng , Wu Bo , Xie Yiyang , Wang Guangcheng , Deng Jinxiang , Zhai Tianrui , Deng Hui-Xiong , Hong Jiawang , Zhao Jianhua
Published: December 2022

Multiferroic materials have great potential in non-volatile devices for low-power and ultra-high density information storage, owing to their unique characteristic of coexisting ferroelectric and ferromagnetic orders. The effective manipulation of their intrinsic anisotropy makes it promising to control the multiple degrees of freedom of the storage "medium". Here, we have discovered intriguing electrical and magnetic anisotropies within the intralayer of CuCrP2S6, a promising van der Waals multiferroic material. The in-plane uniaxial anisotropies of the current rectifications, magnetic properties and magnon modes are demonstrated and manipulated by electric direction/polarity, temperature variation and magnetic field. More important, we have observed spin-flop transition corresponding to specific magnon modes, and it is well supported by theoretical calculations. Our work provides the first observation of electrical and magnetic anisotropies with same easy axis in van der Waals multiferroics, which will stimulate novel device applications of artificial bionic synapses, multi-terminal spintronic chips and magnetoelectric devices.
Platelet Indices and Blood Pressure: A Multivariable Mendelian Randomization Study
Authors: Xu Yuhan , Guo Yijing
Published: December 2022

Background: Platelet indices are blood-based parameters reflecting the activation of platelets. Previous studies have identified an association between platelet indices and blood pressure (BP). However, the causal inferences are prone to be biased by confounding effects and reverse causation. We performed a Mendelian randomization (MR) study to compare the causal roles between genetically determined platelet indices and BP level.
Methods: Single-nucleotide polymorphisms (SNPs) associated with platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), and BP at the level of genomewide significance (p < 5 × 10−8 ) in the UK Biobank were used as instrumental variables. In bi-directional univariable MR analyses, Inverse variance-weighted (IVW), MR-Egger, and weighted median methods were used to obtain estimates for the individual causal power. In addition, heterogeneity and sensitivity analysis was performed to examine the pleiotropy of effect estimates. Finally, multivariable MR analyses were undertaken to disentangle the comparative effects of four platelet indices on blood pressure.
Results: In the univariable MR analyses, Increased levels of PLT and PCT were associated with higher BP, and PDW was associated with higher DBP alone. In the reverse direction, SBP had a minor influence on PLT and PCT. In multivariable MR analysis, PDW and PLT revealed an independent effect, whereas the association for PCT and MPV was insignificant after co-linear correction.
Conclusion: These findings suggest that platelet and BP may affect each other. PDW and PLT are independent platelet indices influencing BP. Increased platelet activation and aggregation may be involved in the pathogenesis of hypertension which may provide insights into evaluating thromboembolic events in people with high BP. The necessity of initiating antiplatelet therapy among hypertension groups need further investigation.
Transcriptome Analysis Reveals Association of Carotenoid Metabolism Pathway with Fruit Color in Melon
Authors: Diao Qiannan , Tian Shoubo , Cao Yanyan , Yao Dongwei , Fan Hongwei , Zhang Yongping
Published: December 2022

Flesh color is an important quality of melon (Cucumis melo L.) and is determined mainly by carotenoid content, awarding them with colors, aromas, and nutrients. enhancing the nutritional and health benefits of fruits and vegetables for humans. In this study, we performed transcriptomic analysis of two melon inbred line “B-14” (orange-flesh) and “B-6” (white-flesh) at three developmental stages. We observed that the β-carotene content of inbred line “B-6” (14.232 μg/g) was significantly lower than that of inbred line “B-14” (0.534 μg/g). RNA-sequencing and quantitative reverse transcription PCR analyses were performed to identify differentially expressed genes (DEGs) between the two inbred lines at different stages; the DEGs were analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes databases (KEGG). We identified 33 structural DEGs in different developmental periods of the two lines that were related to carotenoid metabolism. Among them, PSY, Z-ISO, ZDS, CRTISO, CCD4, VDE1, and NCED2 were highly correlated with carotenoid content. Thus, this study provides a basis for molecular mechanism of carotenoid biosynthesis and flesh color in melon fruit.
ANGPTL8 as an Inflammatory Trigger Aggravated Microglial Pyroptosis in the Pathogenesis of Alzheimer’s Disease
Authors: Wei Jiarui , Hu Lin , Xu Shufan , Li Yifan , Liao Fusheng , Zhang Xiaoqiao , Fang Xingang , Ding Li , Wang Ting , Chen Zhuo , Su Shanchun , Zhang Qiufang , Guo Xingrong
Published: December 2022

Background: Increasing evidence indicates that Alzheimer’s disease (AD) is not only a disease of the brain but also an autoimmune disorder of innate immunity. Pyroptosis-mediated inflammation activates microglia, which are innate immune regulators that play an important role in AD formation. New studies have found that some peripheral proinflammatory cytokines can penetrate the blood–brain barrier (BBB), thereby activating microglial pyroptosis and promoting inflammation in the brain. However, the impact of the liver-brain axis on the development of AD remains elusive. Here, we show that liver-secreted ANGPTL8 acts as an inflammatory trigger and penetrates the BBB, contributing to the progression of AD.
Methods: ANGPTL8-/- mice were crossed with 5×FAD mice to obtain WT, 5×FAD, ANGPTL8-/-, and ANGPTL8-/- 5×FAD mice. We checked whether ANGPTL8 knockout affected learning and memory impairment using the Morris water maze (MWM) task. Tiofavin-S (Tio-S) and Nissl staining were used to analyze amyloid β (Aβ) deposition and the number of neurons in the four groups of mice. The effects of ANGPTL8 on the activation of microglia and neuroinflammation were analyzed in vitro and in vivo by immunofluorescence and flow cytometry. Extracting single-cell sequencing library data and in situ hybridization, etc., were used to analyze the source of ANGPTL8 that promotes AD progression. RNA interference assay, transmission electron microscopy, western blotting, etc., were used to study the mechanisms of ANGPTL8 in regulating AD progression. Finally, drug screening was used to identify an effective inhibitor of ANGPTL8.
Results: ANGPTL8 knockout improved cognitive functions and decreased Ab deposition in 5xFAD mice. ANGPTL8 levels were significantly increased in the livers of 5xFAD mice and upregulated by Aβ stimulation. Secreted Aβ in turn promotes the expression of ANGPTL8, and secreted ANGPTL8 acts as an inflammatory trigger and directly interacts with the microglia membrane receptor PIRB to activate downstream PIRB/NLRP3 signaling, thereby inhibiting the phagocytic capacity of microglia to reduce the clearance of Aβ by promoting pyroptosis. The antidiabetic drug metformin can inhibit the expression of ANGPTL8 and improve the learning and memory of 5xFAD mice.
Conclusions: Our study identified ANGPTL8 as a novel peripheral inflammatory trigger that regulates the liver-brain axis and aggravates microglial pyroptosis via the PIRB/NLRP3 pathway to accelerate the pathogenesis of AD. Our results also indicate that the serum ANGPTL8 level represents a potential diagnostic marker for diseases featuring AD and that targeting ANGPTL8 holds great promise for developing innovative therapies to treat AD.
Bioorthogonal Imaging Uncovers Sex- and Diet-dependent Lipid Metabolic Changes in Drosophila Brain during Aging
Authors: Li Yajuan , Chang Phyllis , Sankaran Shriya , Jang Hongje , Nie Yuhang , Zeng Audrey , Hussain Sahran , Wu Jane , Chen Xu , shi Lingyan
Published: December 2022

Lipid metabolism has been associated with brain aging and is regulated by diet, however, the underlying mechanisms are elusive. Using deuterium water (D2O) probed stimulated Raman scattering (SRS) imaging, we demonstrated brain lipid metabolism in Drosophila manipulated by diet in an age- and sex-dependent manner, and important roles of glial insulin/IGF-1 signaling (IIS) pathway in brain lipid metabolism. High sugar diets enhanced lipogenesis while dietary restriction promotes both lipogenesis and lipolysis, and these effects were impaired in both chico1/+ and dfoxo Drosophila loss-of-function mutants. Lipid synthesis and mobilization in brain lipid droplets were reduced with aging, but old chico1/+ flies maintained high lipid metabolic activities whereas aged dfoxo mutants showed increased lipogenesis in females but decreased lipogenesis in males. Diet-regulated brain lipid metabolism did not show sexual difference in both mutants as that in control. Our study supports the crucial role of glial IIS in regulating brain lipid metabolism.
Weibel Instability in Relativistic-Maxwellian Laser Fusion Plasma
Authors: Belghit Slimen , Zaidi Beddiaf
Published: December 2022

We study the Weibel instability (WI) in plasma heated by a laser pulse in the relativistic regime under Jüttner-Maxwell distribution function (relativistic Maxwellian), for this the basic equation in our model is the relativistic Vlasov equation .we solve the dispersion relation of low frequency and deduce the growth rate of WI. The main obtained result is that the choice of plasma density, quick scale time and electronic temperature can be stabilized the value of growth rate of WI; when shown clearly that the relativistic effect sureties the spectrum of growth rate of WI.
Strength and behavior of CFST columns using M-Sand replacing fine aggregate: Experimental, Theoretical and Numerical analysis
Authors: S.M. Shehnaz , S.M. Imam Shah , G Mohan Ganesh
Published: December 2022

As fine aggregate is becoming the most expensive material due to its scarcity, use of alternate is inevitable. Manufactured Sand (M-Sand) is one such admixture that can be replaced with fine aggregate. 32 Concrete Filled Steel Tubes (CFST) with circular cross section, subjected to axial load without eccentricity, divided in to 4 series and filled with 4 different mixes are presented in this paper. CFST specimens with outer diameter (D) of 76 mm, Diameter to thickness (D/t) of 45.84 and Length to Diameter (L/D) of 7, 8, 9 and 10 were considered. Concrete filled in the specimens had M30 grade with fine aggregate replaced with M-Sand at 0, 15, 20 and 25%. As the replacement of M-Sand increased, concrete compressive strength increased and eventually enhanced the axial carrying capacity of the columns. However, increase in L/D, decreased the column capacity. Impact of axial load on parameters like Strength Index (SI), Confinement (ξ), percentage contribution of steel and concrete are also presented. Further, axial load values of the specimens were compared with design values of Eurocode (EC4), American Code (ACI-318), Australian Code (AS5100) and Japanese Code AIJ codes. Experimental results were very near to EC4 and ACI − 318 design values while remaining codes gave unconservative results. Finally, Finite Element Analysis (FEA) model using ABAQUS software was developed for all the specimens to study the behavior of column capacity, failure mode and displacement curves.
Dynamic analysis of novel multi-link-spring mechanism for vibration isolation and energy harvesting
Authors: Xie Jiaheng , Yang Tao , Tang Jie
Published: December 2022

The study of the effective combination of vibration isolation and energy harvesting (VIEH) has become a popular topic at present. However, due to technical limitation, existed vibration isolator integrated energy harvesters have poor performance at low frequency. Therefore, this paper proposes a new multi-link-spring mechanism (MLSM), which can achieve quiz-zero-stiffness (QZS) and multi-stable characteristic by adjusting the parameters. Subsequently, the VIEH performance of MLSM under harmonic excitation and Gaussian white noise excitation are studied. And then, the influence of different parameters on the VIEH performance of the MLSM is analyzed. It was found that the MLSM can achieve any small stiffness in the equilibrium position and has well vibration isolation performance under low frequency or even ultra-low frequency. The frequency band can be widened by adjusting parameters to achieve higher energy harvesting power. Finally, the MLSM is compared with two special cases. The results show that the new MLSM is basically the same as the other two oscillators in terms of vibration isolation but has better energy harvesting performance under the multi-stable characteristic. The MLSM provided by this paper is expected to reduce the impact of external excitation on high-precision sensitive equipment in special sites such as subway and mine, and at the same time supply power to structural health monitoring device.
Cannabidiol and Trazodone Ameliorate Neuronal Proteotoxicity in C. elegans
Authors: Gilberto Vincenzo S. , McGrath Stephanie , Alsulami Abdullatif M , Vidrio-Aguirre Alexia , Moreno Julie
Published: December 2022

Alzheimer’s disease (AD), typically characterized by the accumulation of the misfolded proteins Amyloid beta (Aβ1-42) and hyperphosphorylation of Tau (P-Tau), is the most common neurodegenerative disease. Although there is currently no cure, research with rodent models has found targeting the signaling pathways involved in reactive oxygen species (ROS) or the unfolded protein response (UPR) can diminish the toxic effects of AD (e.g., behavioral deficits, glial inflammation, and proteotoxicity). For this study, we hypothesized that treatment combining Cannabidiol (CBD) and Trazodone (TRA), would better mitigate neuronal dysfunction and extend the lifespan of nematodes engineered to aggregate toxic misfolded proteins. CBD and TRA have been individually found to diminish the deleterious effects of proteotoxicity in both in vivo and in vitro studies. The organisms utilized in the study included two strains of C. elegans genetically modified to express two pathological proteins of AD. Our experiments revealed that the motility and lifespan of C. elegans with proteotoxicity of either Aβ1-42 or P-tau were significantly improved by treatment with CBD and TRA in combination. We also confirmed aspects of existing research on the efficacy of CBD and TRA individually. Our data suggest that these benefits are seen with full-life, middle-age, and late-stage rescue utilizing CBD and TRA. These findings suggest the need for future experimentation incorporating CBD and TRA in treatment regiments in higher organisms, including neurodegenerative rodent models and aging canines with cognitive decline.
Sublingual Recurring Extra osseous Ewing Sarcoma: A Rare Case Report and Review of Literature
Authors: Amer Hatem , Alaroomy Leena , Ayad Haytham , El-din Yasmine Alaa , Alwadeai Mohamed
Published: December 2022

Background: Extera skeletal (Extraosseous) Ewing sarcoma is a rare primary tumor of the soft tissue, with an extremely high mortality rate and a bad prognosis which primarily affects young individuals. It occurs without particular clinical signs and can impact several different areas, which may delay diagnosis. Histopathological examination and immunohistochemistry are crucial for making a definite diagnosis. Besides this, early diagnosis is necessary for succeeding of the management.
Case report: The objective of the present case report was to document a rare case of EES which originated from the floor of the mouth. A 37-year-old male patient came to our clinic with sublingual rapidly growing swelling. He was suffering from difficulty in opening his mouth and a feeling of dysphagia. The patient revealed during a history-taking procedure that he had undergone one surgery to remove the mass that had previously developed in the same area, knowing that he had been diagnosed in the first as a non-specific inflammatory reaction. Clinical examinations revealed a dome shape soft tissue mass. The biopsy specimen underwent histopathological and immunohistochemical analysis, which demonstrated poorly differentiated small blue round cells with positive immuno-expression of CD-99, NKX2-2, FLI-1, and Vimentin. The final diagnosis was EES based on the clinical presentation, histopathological pattern, and findings of the immunohistochemistry investigations. Radiotherapy and chemotherapy were chosen as treatment modalities for the case. Unfortunately, the patient died after three months due to the occurrence of multiple distant metastasis areas.
Conclusion: Regardless of the relative rarity of Extraosseous Ewing sarcoma, it should be taken into account as a possible differential diagnosis for intraoral soft tissue masses, and accurate diagnosis with precise histopathological and immunohistochemical evaluations should be done as soon as possible. Moreover, improvement of management procedures of such cases generally provides the best chances for patient survival.
Comparison and Evaluation of the Effectiveness of Traditional Neuroanatomy Teaching in Medical Education with Virtual-Reality Application Based On 3D Virtual Neuroanatomical Models, which is an innovative approach
Authors: ALIM Ece , COŞKUN Özlem , PEKER Tuncay Veysel
Published: December 2022

Purpose:Learning the neuroanatomical structures is difficult in traditional medical education. Knowledge and visual materials in neuroanatomy books or atlases are static and limited with two dimensions. The limitation of cadaver and plastic models has been solved by the development of three-dimensional (3D) anatomical models using digital visualization technologies. Medical students are better able to understand the spatial topography of a large number of neuroanatomical structures that are condensed into a small region when they make use of 3D visualization technologies such as virtual reality (VR) and augmented reality (AR). Our study will open a new window to classical neuroanatomy education. We aimed to evaluate how much 3D neuroanatomical models based on VR application affect the success and motivation of medical school students in neuroanatomy courses.
Methods:Four exams were given to the second-year medical faculty students before the classical theoretical course (1), after the theoretical course (2), after the VR training and application (3), and six months later to evaluate the long-term effects of the training (4).
Results:Success averages were evaluated out of 10; It was found 3.38 in the students who participated in the evaluation after the traditional theoretical training, and 4.55 in the group who received VR training. In the long-term evaluation after six months, this average was found to be higher in the group that received VR training.
Conclusion:Our study fills an important gap in the literature in terms of demonstrating the positive effects of VR-based neuroanatomy training on memory in the long term.
Effect of heat treatments on microstructure and mechanical properties of AlSi10Mg alloys fabricated by Laser powder bed fusion
Authors: Zhu Xiaogang , Du Dafan , Dong Anping , Sun Qinyao , Sun Jing , Guo Lijie , Sun Baode , Chen Zhendong
Published: December 2022

This study investigated the microstructures and tensile properties of as-build and heat-treated (including T6, T2 and T6-T2 treatments) AlSi10Mg samples fabricated by laser powder bed fusion (LPBF). The microstructure analysis revealed that the trend of eutectic Al-Si phase distribution along grain boundaries for heat-treated samples was significantly weakened, and the eutectic Al-Si phase was transformed into Si particles which were uniformly distributed in α-Al matrix. For the T6-T2 treated specimens, the Si content in particles was the highest. Meanwhile, the T6 treatment increased the proportion of equiaxed grains on vertical section most significantly. However, in the wake of heat treatments, the average grain size on horizontal section had little change while the average grain size on vertical section was increased. The properties analysis demonstrated that the T6-T2 treated specimens obtained the best elongation and worst strength. Besides, the T6 treatment eliminated the anisotropy of the LPBFed specimens basically, and synergistically obtained the best combination of strength and plasticity. The T6 treatment weakened the direction difference to the greatest extent, whereas the T2 treatment minimized the stress concentration. According to the comparative finding, the Si content in particles played an important part in properties. Besides, the relationship among inverse pole figure (IPF) maps, pole figure (PF) maps, the mass fraction and distribution of Si in Al matrix and Si particle, the grain size, Kernel average misorientation (KAM) and mechanical properties under different heat treatments was established, which provided a new idea for the selection of heat treatments on LPBFed parts.
In vitro and in vivo antifungal activity of chitosan, as continuous gel and nanoparticles suspension, against Alternaria alternata and Penicillium expansum.
Authors:   Taís Téo de Barros-Alexandrino1, Martelli Milena Tosi , Assis Odílio Benedito Garrido
Published: December 2022

Formulations based on chitosan of medium molar mass, in the form of continuous gel and suspension of nanoparticles with average dimensions of 117 ± 20 nm, obtained by crosslinking with sodium tripolyphosphate, were evaluated with respect to the antimicrobial activity against the fungi Alternaria alternata and Penicillium expansum. When essayed in in vitro condition, using the sequential dilution method, the resultant minimum inhibitory concentration (MIC) was 7 gL− 1 for both fungi. In diffusion measurements on solid agar medium, the MIC of 7 gL− 1 was confirmed for the inhibition of A. alternata and 8 gL− 1 was found for P. expansum. Based on these results, the concentration of 9 gL− 1 was chosen for the in vivo tests in the form of coatings on previously inoculated apples and guavas. The coatings were prepared via nebulization, either from the continuous or the nanoparticulate formulation. Fungal counting (CFU) from inoculation day to fruit decay indicated a greater efficiency of the nanoparticulate coating, especially for guava, which is more perishable and susceptible to infestation. By comparison, on apples the coatings have similar initial inhibition. After 20 days of measurements however, the particulate system shows 13% higher efficiency than the continuous coating. For guava, the efficiency of the particulate suspension was even better, 33% higher than the continuous covering, having a significant effect on the extension of the shelf life, with an increase of one week under the experimental storage conditions evaluated (room temperature, RH 50–60%).
Phase 1 study to determine the safety and dosing of autologous PBMCs modified to present HPV16 antigens (SQZ- PBMC-HPV) in HLA-A*02+ patients with HPV16+ Solid Tumors
Authors: Jimeno Antonio , Baranda Joaquina , Iams Wade T. , Park Jong Chul , Mita Monica , Gordon Michael S. , Taylor Matthew , Dhani Neesha , Leal Alexis D. , Neupane Prakash , Eng Cathy , Yeku Oladapo , Mita Alain , Moser Justin C. , Butler Marcus , Loughhead Scott M. , Jennings Julia , Miselis Nathan R. , Ji Rui-Ru , Nair Nitya , Kornacker Martin , Zwirtes Ricardo F. , Bernstein Howard , Sharei Armon
Published: December 2022

Purpose
We conducted a dose escalation Phase 1 study of autologous PBMCs loaded by microfluidic squeezing (Cell Squeeze® technology) with HPV16 E6 and E7 antigens (SQZ-PBMC-HPV), in HLA-A*02 + patients with advanced/metastatic HPV16 + cancers. Preclinical studies in murine models had shown such cells resulted in stimulation and proliferation of antigen specific CD8 + cells, and demonstrated antitumor activity.
Methods
Administration of SQZ-PBMC-HPV was every 3 weeks. Enrollment followed a modified 3 + 3 design with primary objectives to define safety, tolerability, and the recommended Phase 2 dose. Secondary and exploratory objectives were antitumor activity, manufacturing feasibility, and pharmacodynamic evaluation of immune responses.
Results
Eighteen patients were enrolled at doses ranging from 0.5 × 106 to 5.0 × 106 live cells/kg. Manufacture proved feasible and required < 24 h within the overall vein-to-vein time of 1–2 weeks; at the highest dose, a median of 4 doses were administered. No DLTs were observed. Most related TEAEs were Grade 1–2, and one Grade 2 cytokine release syndrome SAE was reported. Tumor biopsies in three patients showed 2 to 8-fold increases in CD8 + tissue infiltrating lymphocytes, including a case that exhibited increased MHC-I + and PD-L1 + cell densities and reduced numbers of HPV + cells. Clinical benefit was documented for the latter case.
Conclusions
SQZ-PBMC-HPV was well tolerated; 5.0 × 106 live cells/kg with double priming was chosen as the recommended Phase 2 dose. Multiple participants exhibited pharmacodynamic changes consistent with immune responses supporting the proposed mechanism of action for SQZ-PBMC-HPV, including patients previously refractory to checkpoint inhibitors.
Active whey protein film containing milk-derived antimicrobial peptide for microbial control in soft cheese
Authors: Zhang Ruyue , Yang Yaling , Wang Bini , Zhang Fuxin , Liu Yufang
Published: December 2022

The aim of this study was to prepare whey protein-based edible films with the incorporation of milk-derived antimicrobial peptides (αs2-casein151 − 181 and αs2-casein182 − 207) and compare their effectiveness on the control of microbiological contamination in soft cheese with edible films containing nisin. These two antimicrobial peptides showed similar activity against B. subtilis and much higher activity against E. coli than bacteriocin nisin, representing that these milk-derived peptides had great potential to be applied as food preservative in dairy products. Antimicrobial peptides in whey protein films caused an increase of film thickness, opaqueness and water vapor barrier properties, but decreased the mechanical properties. Whey protein film incorporated with αs2-casein151 − 181 could inhibit the growth of yeasts and moulds, and control the growth of psychrotrophic bacteria present originally in the soft cheese at refrigerated temperature. It also exhibited the significantly inhibitory activity against the development of a mixed culture (E. coli and B. subtilis) in the cheese due to a superficial contamination during the storage. Antimicrobial peptides immobilized in whey protein films showed a higher effectiveness than its direct application in solution. In addition, films containing αs2-casein151 − 181 could act as a hurdle inhibiting the development of postprocessing contamination on the cheese surface during the 28 days of storage. Development of antimicrobial packaging on the basis of whey protein could be one effective way to reduce environment unfriendly plastic and whey protein waste for further application.
Transcriptomic Insight Based on Network Analysis Reveals the Effect of Ursolic Acid on Non-Alcoholic Steatohepatitis
Authors: Xue Chun-yan , Wu Ling , Rao Chen-yi , Huang Xiao-quan , Chen Shi-yao , Li Feng
Published: December 2022

Background
Non-alcoholic steatohepatitis (NASH) has attracted international attention. However, pharmaceutical treatments are not included in the current guidelines. Ursolic acid (UA) has the potential to treat metabolic disorders. Hence, this study aimed to investigate the impact of UA on NASH.
Methods
RNA sequencing from our own model mice was performed to detect differentially expressed genes (DEGs) in 12 mouse samples from 4 groups. DEGs were subjected to Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was applied to find modules associated with NASH's pathological characteristics and identified the hub genes in the relevant modules. Hub genes were further identified and the ceRNA network was constructed. In vitro and in vivo experiments were applied to identify the expected mRNAs.
Results
By comparing NASH mice to Wild type (WT) mice, we performed GO and KEGG enrichment analysis to identify pathways associated with NASH inflammatory metabolic disorders, and by doing the same for NASH mice treated with UA, we identified pathways via which UA may alter. Based on WGCNA, the modules associated with the pathological changes of NASH, as well as the hub genes in each module were identified. A ceRNA network was successfully constructed. RT-PCR results showed that Akr1a1 and Chchd2 were protective factors against NASH, and Ndufb9 was a risk factor. The level of ROS detected by flow cytometry indicated that UA could alleviate oxidative stress.
Conclusion
Akr1a1, Chchd2, and Ndufb9 were essential for the therapeutic effects of UA on NASH and the ceRNA network might act as prospective therapeutic and diagnostic biomarker targets.
Diosmin nanocrystals alleviate Imiquimod induced psoriasis in rats via modulating TLR7,8/ NF-κB/micro RNA-31, AKT/mTOR/P70S6K milieu and Tregs / Th17 balance
Authors: Shahine Yasmine , El-Aal Sarah A. Abd , Reda Ahmed M. , Sheta Eman , Attia Nouran M. , Abdallah Ossama Y. , ibrahim Sherihan salaheldin abdelhamid
Published: December 2022

Diosmin is a flavonoidal compound characterized by highly challenging physicochemical properties. There wasn’t enough attention paid for using diosmin topically in spite of its strong anti-inflammatory and anti-oxidant properties. The aim of this work is the development and characterization of diosmin nanocrystals using anti-solvent precipitation technique to be used for topical treatment of psoriasis. Evaluation of different stabilizers with different concentrations to achieve the most stable nanocrystals was studied. Results revealed that diosmin nanocrystals stabilized with hydroxypropyl methylcellulose (HPMC E15) in weight ratio (diosmin:polymer 1:1) could reach the desired particle size (276.9 ± 16.49 nm); provided the promising colloidal properties and higher drug release profile. In-vivo assessment was carried out to evaluate and compare the activities of diosmin nanocrystals gel using 3 different doses and diosmin powder gel in alleviating imiquimod induced psoriasis in rats and investigating their possible anti-inflammatory mechanisms. Herein, 125 mg of 5% imiquimod cream (IMQ) was applied topically for 5 consecutive days on the shaved backs of rats to induce psoriasis. Diosmin nanocrystals gel especially in the highest dose used offered the best anti-inflammatory effect. This was confirmed by causing the most significant mitigation in the psoriasis area severity index (PASI) score and the serum inflammatory cytokines levels (IL17A, IL23, and IL22). Furthermore, it was capable of maintaining balance between Th17 and Treg cells by decreasing the immunohistochemical expression of RORγ and increasing that of FOXP3. Moreover, it tackled TLR7/8/NF-κB, AKT/mTOR/P70S6K and elevated the TNFAIP3/A20 (negative regulator of NF-κB) expression in psoriatic skin tissues. Also, it abrogated the tissue expression of PCNA, BCL-2 and miRNA-31 level. This highlights the role of diosmin nanocrystals gel in tackling imiquimod induced psoriasis in rats via modulating TLR7,8/NF-κB/miRNA-31, AKT/mTOR/P70S6K milieu and Tregs/Th17 balance. Therefore, it is suggested that diosmin nanocrystals gel could be a novel promising therapy for psoriasis.
Changes in the exposure to power saw noise during individual partial activities of tree felling in dependence on the stem wood moisture content
Authors: Staněk Luboš , Mergl Václav , Neruda Jindřich
Published: December 2022

This study deals with the level of noise to which power saw operators are exposed during partial activities of tree felling and persons moving in its surroundings. It also aims to reveal the existence of dependence between the level of produced noise and the moisture content of the felled tree by comparing the noise levels of individual partial activities. The process of tree felling was broken down into partial activities (pruning of the lower tree part; cutting off buttresses; felling; delimbing) during which exposure to noise caused by the power saw was measured. The noise was measured by the noise level meter at the operator’s ear at distances of 5 m and 10 m from the source of noise (power saw) in compliance with EN ISO 22868 and EN ISO 9612 standards. The noise was measured in a total of 121 trees processed by one power saw operator using one and the same type of power saw and one and the same type of saw chain. Research results revealed a noise level difference of individual operations in 88.10% of compared cases. Mean noise levels close to the operator’s ear ranged from 95,193.499 dB to 101,098.174 dB and mean noise values at a distance of 10 m ranged from 70,573.677 dB to 78,370.818 dB. A maximum noise level (115,720.000 dB) was measured during the partial operation of Delimbing near the operator’s ear; a minimum noise level (51,650000 dB) was recorded during this operation, too.
Conflict-free, fault-tolerant, and compact programmable switching unit
Authors:   National Research Tomsk Polytechnic University (NR TPU), A. I. Soldatov , O. H. Kim ,   Tomsk State University of Control Systems and Radioelectronics (TUSUR), A. A. Soldatov ,   National Research Tomsk Polytechnic University (NR TPU), M. A. Kostina ,   National Research Tomsk Polytechnic University (NR TPU), G. N. Narimanova ,   Tomsk State University of Control Systems and Radioelectronics (TUSUR)
Published: December 2022

The article provides a technical solution for building a switching unit. Its conflict-free nature, fault tolerance, and compactness are investigated. Using the example of a 16-pin switching unit, it is shown that the proposed structure allows performing electrical connections with 100% use of external pins. Two options for implementing 8 circuits on a 16-pin switching unit are given. The fault tolerance is shown. The proposed approach to building a switching unit allows to implement a switching unit of any size with a reduced number of switch elements.
Adjusting robust neural networks for solving the classification problem
Authors:   Novosibirsk State Technical University (NSTU), Sivak M. A. , Timofeev V. S. ,   Novosibirsk State Technical University (NSTU)
Published: December 2022

The paper highlights the problem of building and adjusting robust neural networks applying different loss functions for solving the classification problem. The considered functions are those of Cauchy, Meshalkin, Geman-McCluer, Charbonnier and Tukey’s Biweight losses. The accuracy of classification is examined for the different values of outliers’ fraction, for several values of learning epochs count and for datasets with various sizes. For all obtained networks the parameter values that maximize the accuracy, are defined. The best practices for choosing the parameter values depending on epoch count are also defined for all the loss functions. The ordinary neural network (with quadratic loss) and the robust neural network applying the Huber loss are also considered. The analysis of the results shows that the use of robust approach can significantly increase the learning rate and the classification accuracy, however, choosing the incorrect parameter value can decrease the accuracy of classification.
Math model for estimating the probability of preambles collisions within random access in the mMTC scenario
Authors:   Tomsk State University of Control Systems and Radioelectronics (TUSUR), Kryukov Ya. V. , Pokamestov D. A. ,   Tomsk State University of Control Systems and Radioelectronics (TUSUR), Rogozhnikov E. V. ,   Tomsk State University of Control Systems and Radioelectronics (TUSUR), Novichkov S. А. ,   «5G Open Radio Access Networks», Skoltech, Lakontsev D. V. ,   N«The Wireless Network Technologies and Internet of Things», Skoltech
Published: December 2022

The mass machine-to-machine communication (mMTC) scenario is one of the key ones in 5G cellular communication system. Tens of thousands of devices can operate simultaneously in one mMTC cell, sending data asynchronously to the data collection point. This is the reason for the occurrence of unavoidable collisions of preamble in the random access procedure. Mathematical models of traffic generation from a large number of devices within a cell are used to reliably estimate the probability of collisions. Most existing models are based on the approach of generating aggregated traffic from all devices and do not allow taking into account the current state of each individual device, which reduces the reliability of model studies. To solve this problem, we propose a mathematical model for generating traffic (preambles) in a random access channel, taking into account the transition state matrix of a discrete Markov chain. This approach allows to describe more reliably the synchronous and asynchronous transmission of preambles within a cell. The developed model is designed to estimate the collision probability of the random access procedure in the mMTC scenario, taking into account the synchronous and asynchronous transmission of preambles.
Estimation of the relation between the correlator length and the number of subscribers in a communication system with digital pseudo-random modulation
Authors:   National Research Tomsk State University (NR TSU), Kokin D. S. , Ponomarev O. G. ,   National Research Tomsk State University (NR TSU)
Published: December 2022

This article examines one of the options for implementing a communication system with pseudo-random digital modulation. For such systems the spreading factor (the signal base) is an important parameter. This work contains the results of operability study for the system in multi-user radio channel. During numerical simulation it was established how the correlator length depends on the number of users simultaneously working in the common frequency band. It is shown that this dependence has a quadratic character.
Technique for clustering agricultural fields based on RGB-images shot by unmanned aerial vehicles
Authors:   Tomsk State University of Control Systems and Radioelectronics (TUSUR), Kataev M. Yu. , Kartashov E. Yu. ,   Seversk Technological Institute of the National Research Nuclear University «MEPhI», Kuznetsov A. A. ,   Tomsk State University of Control Systems and Radioelectronics (TUSUR)
Published: December 2022

The Earth remote sensing (ERS) technologies, that are being developed on the basis of satellite sensing and, more recently, unmanned aerial vehicles (UAVs), provide a significant potential for smart (precision) farming applications. Sensors (for example, digital RGB cameras) provide real-time data about the environment of the study area in the form of images. The sensors installed on unmanned aerial vehicles can be used in various applications related to assessing the quality of plowing, winter wheat seedlings, growing crops, etc. It becomes possible because they capture large areas with a set of images with a low time (several hours per 1000 hectares), but with a high spatial resolution (several centimeters). The remote sensing technology is expected to revolutionize the agriculture by enabling faster decision-making limited by few days only, as well as reducing costs and increasing yields. Despite the significant development, one of the areas of use of UAVs in smart agriculture is not yet as reliable and accurate as expected, mainly due to problems arising in the collection, processing and analysis of images. The main problem is that there is still no standardized workflow that includes the steps from collection to visualization of results when using UAVs in agricultural applications. One of the weak points of many image processing technologies is the insufficient quality of clustering, where each cluster found is associated with a certain type of surface. This article discusses the use of images obtained using UAVs for solving the challenges of smart agriculture. A clustering technique related to the parametric representation of histograms of brightness of color spaces and Greenness Indexes is discussed. The results of image processing are presented.
Information system to support an advanced training of personnel for a monotown: concept, functions and composition of modules
Authors:   Tomsk State University of Control Systems and Radioelectronics (TUSUR), Zakharova A. A. , Zakharov L. Yu. ,   Tomsk State University of Control Systems and Radioelectronics (TUSUR)
Published: December 2022

The work considers one of the most important aspects for the development of monotowns in modern conditions - the creation of a system to enables an advanced training of personnel for monotown (SATPM), and ensures the implementation of the chosen strategy of a single-industry city. The task to develop a comprehensive methodological base and software environment is set up. This environment provides a network interaction of educational institutions, employers, administration of a monotown, and its population (individuals), as well as a support tool for decision-making processes in accordance with its tasks and requirements. Based on the criteria and information needs of SATPM entities making decisions, conceptual methodological principles of software development are formulated. The results of functional modeling of the information system of advanced training for monotown, the composition of the modules and the technology of their interaction are presented.
Statistical models for enterprise compensation system
Authors:   Tomsk State University of Control Systems and Radioelectronics (TUSUR), Mitsel A. A. , Shilnikov A. S. ,   Tomsk State University of Control Systems and Radioelectronics (TUSUR)
Published: December 2022

The article discusses the topic of simulation modeling for compensation system (CS). These models are used as a core of the decision-making system (DSS) for the needs of compensation. The authors propose two solutions for compensation plan modeling: 1) Conceiving analytical statistical model; 2) Developing simulation model. The second solution is presented in the article. Some particular CS models are put forward. Based on the obtained synthetic data, following results are achieved: 1) probability densities functions of different CS result indicators are defined; 2) statistical characteristics of CS indicators are reviewed; 3) probability of CS efficiency is measured.
Non-parametric algorithm of processing the signals in the phase direction finders with the linear aerial array
Authors:   OJSC «NIIAP», Novosibirsk, Porubov G. G. , V. P. Denisov ,   Tomsk State University of Control Systems and Radioelectronics (TUSUR)
Published: December 2022

The algorithm of estimating the bearing according to a set of differences of the signal phases measured between the elements of the aerial system is suggested. It is not necessary to know the distribution of the probabilities of the phase errors. The peculiarity of the algorithm is that there is no process of eliminating the ambiguity of the phase measurements and of restoring the total phase differences as a separate operation.