bluuebunny/crossref_metadata_2025 huggingface dataset:
Development, Identification and Validation of a Novel SSR Molecular Marker for Heat Resistance of Grapes Based on miRNA
Authors: Zhang Lipeng , Song Yue , Li Junpeng , Liu Jingjing , Zhang Zhen , Xu Yuanyuan , Fan Dongying , Liu Mingying , Ren Yi , Xi Xiaojun , Chen Qiuju , He Juan , Xu Wenping , Song Shiren , Liu Huaifeng , Ma Chao
Published: August 2023

The adverse effects of high temperatures on fruit quality and yield have been reported in many studies of grapevines. MiRNAs play crucial roles in plant growth and development and also fulfill functions in regulating the high-temperature response. In this research, miRNA-based SSR (simple sequence repeat) polymorphisms were analyzed according to the grape genome sequence and then combined with polymerase chain reaction (PCR) amplification and Sanger sequencing methods to analyze the miRNA-SSR diversity of different heat-resistant grape varieties. A statistical analysis of SSR sequences showed that 391 and 12 SSRs were specific to pri-miRNA and pre-miRNA, respectively. In pri-miRNA containing SSR, hexa-nucleotide repeats were the most abundant (52.69%), followed by tetra-nucleotide (13.04%) and minimum penta-nucleotide (4.09%), which were also observed in pre-miRNA sequences. On the other hand, differences in heat resistance among grape varieties were observed. Based on the results of leaf Fv/Fm images, values and phenotypic changes under high-temperature stress, 20 heat-resistant (e.g., Niagara Rosada and Grand Noir) and 20 heat-sensitive (e.g., Shine Muscat and Jumeigui) grape varieties were identified. Further, PCR-Sanger sequencing was used to screen SSR differences in four thermos-tolerant and four thermos-sensitive grape varieties, and finally, eight SSR differential primers were found to be able to distinguish these varieties. Of these, four pairs of primers were selected for validation in 40 grape germplasm resources (20 thermo-tolerance and 20 thermo-sensitivity). The VMIRSSR167c3 highlights that the ratio of SSR (CT) repeat values greater than 17 in heat-resistant varieties was 90%. In conclusion, the VMIRSSR167c3 marker can accurately distinguish between heat-resistant and heat-sensitive grape varieties. The results provide a novel molecular marker for the genetic improvement of grape germplasm resources and will be beneficial to the breeding of heat-resistant varieties in the future.
N-Acetyl-L-glutamate Kinase of Chlamydomonas reinhardtii: In Vivo Regulation by PII Protein and Beyond
Authors: Vlasova Vitalina , Lapina Tatiana , Statinov Vladislav , Ermilova Elena
Published: August 2023

N-Acetyl-L-glutamate kinase (NAGK) catalyzes the rate-limiting step in the ornithine/arginine biosynthesis pathway in eukaryotic and bacterial oxygenic phototrophs. NAGK is the most highly conserved target of the PII signal transduction protein in Cyanobacteria and Archaeplastida (red algae and Chlorophyta). However, there is still much to be learned about how NAGK is regulated in vivo. The use of unicellular green alga Chlamydomonas reinhardtii as a model system has already been instrumental in identifying several key regulation mechanisms that control nitrogen (N) metabolism. With a combination of molecular-genetic and biochemical approaches, we show the existence of the complex CrNAGK control at the transcriptional level, which is dependent on N source and N availability. In growing cells, CrNAGK requires CrPII to properly sense the feedback inhibitor arginine. Moreover, we provide primary evidence that CrPII is only partly responsible for regulating CrNAGK activity to adapt to changing nutritional conditions. Collectively, our results suggest that in vivo CrNAGK is tuned at the transcriptional and post-translational levels, and CrPII and additional as yet unknown factor(s) are integral parts of this regulation.
A Re-Purposing Strategy: Sub-Lethal Concentrations of an Eicosanoid Derived from the Omega-3-Polyunsaturated Fatty Acid Resolvin D1 Affect Dual Species Biofilms
Authors: Maione Angela , Buonanno Annalisa , Galdiero Marilena , de Alteriis Elisabetta , Petrillo Francesco , Reibaldi Michele , Guida Marco , Galdiero Emilia
Published: August 2023

The fungal species Candida parapsilosis and the bacterial species Staphylococcus aureus may be responsible for hospital-acquired infections in patients undergoing invasive medical interventions or surgical procedures and often coinfect critically ill patients in complicating polymicrobial biofilms. The efficacy of the re-purposing therapy has recently been reported as an alternative to be used. PUFAs (polyunsaturated fatty acids) may be used alone or in combination with currently available traditional antimicrobials to prevent and manage various infections overcoming antimicrobial resistance. The objectives of the study were to evaluate the effects of Resolvin D1 (RvD1) as an antimicrobial on S. aureus and C. parapsilosis, as well as the activity against the mixed biofilm of the same two species. Microdilution assays and time–kill growth curves revealed bacterial and fungal inhibition at minimum concentration values between 5 and 10 μg mL−1. In single-species structures, an inhibition of 55% and 42% was reported for S. aureus and C. parapsilosis, respectively. Moreover, RvD1 demonstrated an eradication capacity of 60% and 80% for single- and mixed-species biofilms, respectively. In association with the inhibition activity, a downregulation of genes involved in biofilm formation as well as ROS accumulation was observed. Eradication capability was confirmed also on mature mixed biofilm grown on silicone platelets as shown by scanning electron microscopy (SEM). In conclusion, RvD1 was efficient against mono and polymicrobial biofilms in vitro, being a promising alternative for the treatment of mixed bacterial/fungal infections.
Comprehensive Analysis of Ferroptosis Regulators with Regard to PD-L1 and Immune Infiltration in Low-Grade Glioma
Authors: Luan Yuxuan , Chen Yuling , Wang Yilin , Shu Minfeng
Published: August 2023

The prognosis of low-grade glioma (LGG) is highly variable and requires more accurate predictors. Ferroptosis, a newly discovered programmed cell death, has been demonstrated to play a crucial role in some types of tumors. However, prognostic prediction based on ferroptosis-related genes (FRGs) and the influence on the tumor microenvironment (TME) in LGG remains elusive. We derived expression profiles for LGG from public databases. Based on the expression of 25 FRGs in LGG, two independent subtypes and a risk model were successfully constructed. Different methods were applied to assess the tumor heterogeneity, tumor microenvironment, and the prognostic value. In addition, a competing endogenous RNA (ceRNA) regulatory axis was constructed. The subtypes had independent tumor heterogeneity, tumor microenvironments, and prognoses. LPCAT3, SLC1A5, HSPA5, and NFE2L2 were identified as the potential prognostic FRGs. Based on these four FRGs, our risk model possesses excellent potential to predict prognosis and varied immune infiltration abundance. The ceRNA regulatory axis provides a potential therapeutic target for LGG. Our molecular subtypes, risk model, and ceRNA regulatory axis have strong immune prediction and prognostic prediction capabilities which could guide LGG treatment.
Interleukin-13 (IL-13)—A Pleiotropic Cytokine Involved in Wound Healing and Fibrosis
Authors: Roeb Elke
Published: August 2023

The liver, as a central metabolic organ, is systemically linked to metabolic–inflammatory diseases. In the pathogenesis of the metabolic syndrome, inflammatory and metabolic interactions between the intestine, liver, and adipose tissue lead to the progression of hepatic steatosis to metabolic-dysfunction-associated steatohepatitis (MASH) and consecutive MASH-induced fibrosis. Clinical and animal studies revealed that IL-13 might be protective in the development of MASH through both the preservation of metabolic functions and Th2-polarized inflammation in the liver and the adipose tissue. In contrast, IL-13-associated loss of mucosal gut barrier function and IL-13-associated enhanced hepatic fibrosis may contribute to the progression of MASH. However, there are only a few publications on the effect of IL-13 on metabolic diseases and possible therapies to influence them. In this review article, different aspects of IL-13-associated effects on the liver and metabolic liver diseases, which are partly contradictory, are summarized and discussed on the basis of the recent literature.
Genome-Wide Identification and Expression Analysis of C3H Zinc Finger Family in Potato (Solanum tuberosum L.)
Authors: Deng Zeyi , Yang Zhijiang , Liu Xinyan , Dai Xiumei , Zhang Jiankui , Deng Kexuan
Published: August 2023

Transcription factors containing a CCCH structure (C3H) play important roles in plant growth and development, and their stress response, but research on the C3H gene family in potato has not been reported yet. In this study, we used bioinformatics to identify 50 C3H genes in potato and named them StC3H-1 to StC3H-50 according to their location on chromosomes, and we analyzed their physical and chemical properties, chromosome location, phylogenetic relationship, gene structure, collinearity relationship, and cis-regulatory element. The gene expression pattern analysis showed that many StC3H genes are involved in potato growth and development, and their response to diverse environmental stresses. Furthermore, RT-qPCR data showed that the expression of many StC3H genes was induced by high temperatures, indicating that StC3H genes may play important roles in potato response to heat stress. In addition, Some StC3H genes were predominantly expressed in the stolon and developing tubers, suggesting that these StC3H genes may be involved in the regulation of tuber development. Together, these results provide new information on StC3H genes and will be helpful for further revealing the function of StC3H genes in the heat stress response and tuber development in potato.
CXCR4 Expressed by Tumor-Infiltrating B Cells in Gastric Cancer Related to Survival in the Tumor Microenvironment: An Analysis Combining Single-Cell RNA Sequencing with Bulk RNA Sequencing
Authors: Su Chen , Yu Rong , Hong Xiaoquan , Zhang Panpan , Guo Yingying , Cai Jian-Chun , Hou Jingjing
Published: August 2023

According to the World Health Organization (WHO), gastric cancer (GC) is the fourth leading cause of tumor-related mortality globally and one of the most prevalent malignant tumors. To better understand the role of tumor-infiltrating B cells (TIBs) in GC, this work used single-cell RNA sequencing (scRNA-Seq) and bulk RNA sequencing (bulk RNA-Seq) data to identify candidate hub genes. Both scRNA-Seq and bulk RNA-Seq data for stomach adenocarcinoma (STAD) were obtained from the GEO and TCGA databases, respectively. Using scRNA-seq data, the FindNeighbors and FindClusters tools were used to group the cells into distinct groups. Immune cell clusters were sought in the massive RNA-seq expression matrix using the single-sample gene set enrichment analysis (ssGSEA). The expression profiles were used in Weighted Gene Coexpression Network Analysis (WGCNA) to build TCGA’s gene coexpression networks. Next, univariate Cox regression, LASSO regression, and Kaplan–Meier analyses were used to identify hub genes in scRNA-seq data from sequential B-cell analyses. Finally, we examined the correlation between the hub genes and TIBs utilizing the TISIDB database. We confirmed the immune-related markers in clinical validation samples using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). 15 cell clusters were classified in the scRNA-seq database. According to the WGCNA findings, the green module is most associated with cancer and B cells. The intersection of 12 genes in two separate datasets (scRNA and bulk) was attained for further analysis. However, survival studies revealed that increased C-X-C motif chemokine receptor 4 (CXCR4) expression was linked to worse overall survival. CXCR4 expression is correlated with active, immature, and memory B cells in STAD were identified. Finally, RT-PCR and IHC assays verified that in GC, CXCR4 is overexpressed, and its expression level correlates with TIBs. We used scRNA-Seq and bulk RNA-Seq to study STAD’s cellular composition. We found that CXCR4 is highly expressed by TIBs in GC, suggesting that it may serve as a hub gene for these cells and a starting point for future research into the molecular mechanisms by which these immune cells gain access to tumors and potentially identify therapeutic targets.
Regulation of Smooth Muscle Cell Proliferation by Mitochondrial Ca2+ in Type 2 Diabetes
Authors: Koval Olha M. , Nguyen Emily K. , Mittauer Dylan J. , Ait-Aissa Karima , Chinchankar William C. , Grumbach Isabella M.
Published: August 2023

Type 2 diabetes (T2D) is associated with increased risk of atherosclerotic vascular disease due to excessive vascular smooth muscle cell (VSMC) proliferation. Here, we investigated the role of mitochondrial dysfunction and Ca2+ levels in VSMC proliferation in T2D. VSMCs were isolated from normoglycemic and T2D-like mice induced by diet. The effects of mitochondrial Ca2+ uptake were studied using mice with selectively inhibited mitochondrial Ca2+/calmodulin-dependent kinase II (mtCaMKII) in VSMCs. Mitochondrial transition pore (mPTP) was blocked using ER-000444793. VSMCs from T2D compared to normoglycemic mice exhibited increased proliferation and baseline cytosolic Ca2+ levels ([Ca2+]cyto). T2D cells displayed lower endoplasmic reticulum Ca2+ levels, reduced mitochondrial Ca2+ entry, and increased Ca2+ leakage through the mPTP. Mitochondrial and cytosolic Ca2+ transients were diminished in T2D cells upon platelet-derived growth factor (PDGF) administration. Inhibiting mitochondrial Ca2+ uptake or the mPTP reduced VSMC proliferation in T2D, but had contrasting effects on [Ca2+]cyto. In T2D VSMCs, enhanced activation of Erk1/2 and its upstream regulators was observed, driven by elevated [Ca2+]cyto. Inhibiting mtCaMKII worsened the Ca2+ imbalance by blocking mitochondrial Ca2+ entry, leading to further increases in [Ca2+]cyto and Erk1/2 hyperactivation. Under these conditions, PDGF had no effect on VSMC proliferation. Inhibiting Ca2+-dependent signaling in the cytosol reduced excessive Erk1/2 activation and VSMC proliferation. Our findings suggest that altered Ca2+ handling drives enhanced VSMC proliferation in T2D, with mitochondrial dysfunction contributing to this process.
Circulating Concentrations of Cathelicidin Anti-Microbial Peptide (CAMP) Are Increased during Oral Glucose Tolerance Test
Authors: Höpfinger Alexandra , Karrasch Thomas , Schäffler Andreas , Schmid Andreas
Published: August 2023

Recent investigation has revealed the significant role of Cathelicidin antimicrobial peptide (CAMP) in infection defense and innate immunity processes in adipose tissue. Meanwhile, knowledge of its regulation and functions in metabolic contexts as an adipokine remains sparce. The present study investigated the postprandial regulation of circulating CAMP levels during oral glucose tolerance tests (OGTTs). Eighty-six metabolically healthy volunteers participated in a standardized 75 g-2 h-OGTT setting. The effects of exogenous glucose, insulin, and incretins on CAMP expression in human adipocyte culture (cell-line SGBS) were studied in vitro. CAMP concentrations in blood serum samples were measured by ELISA techniques and adipocyte gene expression levels were quantified by real-time PCR. Of note, base-line CAMP serum quantities were negatively correlated with HDL cholesterol levels as well as with the anti-inflammatory adipokine adiponectin. During the 2 h following glucose ingestion, a significant rise in circulating CAMP concentrations was observed in considerable contrast to reduced quantities of fatty acid binding proteins (FABP) 2 and 4 and dipeptidyl peptidase 4 (DPP4). In SGBS adipocytes, neither differing glucose levels nor insulin or incretin treatment significantly induced CAMP mRNA levels. According to our data, glucose represents a positive postprandial regulator of systemic CAMP. This effect apparently is not mediated by the regulatory impact of glucose metabolism on adipocyte CAMP expression.
Hedgehog-Related Mutation Causes Bone Malformations with or without Hereditary Gene Mutations
Authors: Onodera Shoko , Azuma Toshifumi
Published: August 2023

The hedgehog (Hh) family consists of numerous signaling mediators that play important roles at various stages of development. Thus, the Hh pathway is essential for bone tissue development and tumorigenesis. Gorlin syndrome is a skeletal and tumorigenic disorder caused by gain-of-function mutations in Hh signaling. In this review, we first present the phenotype of Gorlin syndrome and the relationship between genotype and phenotype in bone and craniofacial tissues, including the causative gene as well as other Hh-related genes. Next, the importance of new diagnostic methods using next-generation sequencing and multiple gene panels will be discussed. We summarize Hh-related genetic disorders, including cilia disease, and the genetics of Hh-related bone diseases.
Early Wearing-Off Effect of OnabotulinumtoxinA in Chronic Migraine: A Prospective Real-Life Study
Authors: Rodríguez-Montolio Joana , Navarro-Pérez María Pilar , Almeida-Zurita Monserrath , Santos-Lasaosa Sonia
Published: August 2023

Objective: Chronic migraine (CM) is a significant public health problem that affects 2.2% of the global population. Onabotulinumtoxin A (OnabotA) is a safe and effective prophylactic treatment for patients with CM. The standard injection interval for OnabotA is 12 weeks. Nevertheless, some patients experience a wearing-off effect (WOE) in the weeks preceding the next scheduled cycle. The objectives of this study are to determine the prevalence of early WOE, to analyze variables that could be clinical predictors and to specify which interval is the most appropriate to define the existence of this phenomenon. Methods: This is a prospective single-center study of consecutive adult patients with CM who, after failing previous prophylactic therapies, started OnabotA treatment following the PREEMPT protocol between June and December of 2021. Results: A total of 59 patients (93.2% female, age 44 ± 12 years) were included. A total of 37 patients (64.9%) fulfilled medication overuse criteria. Of the total patients, 40.6% reported WOE and this was more frequent after the first cycle (35.6%). Depression and anxiety disorder was a statistically significant clinical predictor of WOE (OR 3.4; CI 95% 1.22–10.84; p = 0.028). A better cut-off point to consider WOE seems to be at 10 weeks. Conclusions: Early WOE is common in patients on OnabotA treatment for CM. Individualizing the standard 12-week injection, using total doses of 195 U, and managing psychiatric comorbidities with pharmacological and non-pharmacological strategies may improve treatment outcomes and reduce OnabotA WOE.
Promising Materials in the Fight against Healthcare-Associated Infections: Antibacterial Properties of Chitosan-Polyhedral Oligomeric Silsesquioxanes Hybrid Hydrogels
Authors: Laganà Antonio , Facciolà Alessio , Iannazzo Daniela , Celesti Consuelo , Polimeni Evelina , Biondo Carmelo , Di Pietro Angela , Visalli Giuseppa
Published: August 2023

New technologies and materials could help in this fight against healthcare-associated infections. As the majority of these infections are caused by antibiotic-resistant bacteria, the development of materials with intrinsic antibacterial properties is a promising field of research. We combined chitosan (CS), with antibacterial properties, with polyhedral oligomeric silsesquioxanes (POSS), a biocompatible polymer with physico-chemical, mechanical, and rheological properties, creating a hydrogel using cross-linking agent genipin. The antibacterial properties of CS and CS-POSS hydrogels were investigated against nosocomial Gram-positive and Gram-negative bacteria both in terms of membrane damage and surface charge variations, and finally, the anti-biofilm property was studied through confocal microscopy. Both materials showed a good antibacterial capacity against all analyzed strains, both in suspension, with % decreases between 36.36 and 73.58 for CS and 29.86 and 66.04 for CS-POSS, and in plates with % decreases between 55.29 and 78.32 and 17.00 and 53.99 for CS and CS-POSS, respectively. The treated strains compared to the baseline condition showed an important membrane damage, which also determined a variation of surface charges, and finally, for both hydrogels, a remarkable anti-biofilm property was highlighted. Our findings showed a possible future use of these biocompatible materials in the manufacture of medical and surgical devices with intrinsic antibacterial and anti-biofilm properties.
Comprehensive Molecular Evaluation of HNF-1 Alpha, miR-27a, and miR-146 Gene Variants and Their Link with Predisposition and Progression in Type 2 Diabetes Patients
Authors: Mir Rashid , Elfaki Imadeldin , Elangeeb M. E. , Moawadh Mamdoh S. , Tayeb Faris Jamal , Barnawi Jameel , Albalawi Ibrahim Altedlawi , Alharbi Amnah A. , Alhelali Marwan H. , Alsaedi Basim S. O.
Published: August 2023

Background: Type 2 diabetes (T2D) is a metabolic condition induced by insulin resistance and pancreatic beta cell dysfunction. MicroRNAs (miRNAs) have biological significance because they regulate processes such as the molecular signaling pathways involved in the pathophysiology of diabetes mellitus. The hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a transcription factor found in hepatocytes and the pancreas. Mutations in the HNF-1 alpha gene were reportedly associated with maturity-onset diabetes of the young (MODY). The objective of the present study was to examine the associations between MiR-27a, MiR-146, and HNF-1 alpha single-nucleotide variations (SNVs) with T2D risk in the Saudi population. Methodology: We evaluated the association of SNVs of miR-27a rs895819 A>G, 146a-rs2910164 C>G, and HNF-1 alpha rs1169288 G>T (I27L) with the risk of T2D in Saudi patients with the Amplification Refractory Mutation System PCR (ARMS-PCR). For the miR-27a SNVs, we used 115 cases (82 males, 33 females) and 117 matched healthy controls (HCs); for the Mir-146 SNVs, we used 103 cases (70 males, 33 females) and 108 matched HCs; and for the HNF-1 alpha, we employed 110 patients (80 males, 30 females) and 110 HCs. The blood biochemistry of the participants was essayed using commercial kits, and the methods of statistical analysis used were the Chi-square test, the Fisher exact test, and a multivariate analysis based on logistic regression, like the odds ratio (OD) and risk ratio (RR), with 95% confidence intervals (CIs). Results: The MiR-27a rs895819 AG genotype was linked to increased T2D susceptibility, with OR = 2.01 and p-value = 0.011, and the miR-146 rs2910164 CG genotype and C allele were linked to an elevated risk of T2D, with OR = 2.75, p-value < 0.0016, OR = 1.77, and p-value = 0.004. The results also showed that the GT genotype and T allele of the HNF-1 alpha (rs1169288) G>T is linked to T2D, with OR = 2.18, p-value = 0.0061, and 1.77, p-value = 0.0059. Conclusions: The SNVs in miR-27a, miR-146, and HNF-1 alpha can be potential loci for T2D risk. The limitations of this study include the relatively small sample size and the fact that it was a cross-sectional study. To our knowledge, this is the first study to highlight the association between miR-27a, miR-146, and HNF-1 alpha SNVs and the risk of T2D in the Saudi population. Future large-scale case–control studies, as well as studies on the functions of the proteins and protein interaction studies for HNF-1 alpha, are required to verify our findings. Furthermore, these findings can be used for the identification and stratification of at-risk populations via genetic testing for T2D-prevention strategies.
Sciatic Nerve Compression after a Chronic Proximal Hamstring Tear: A Report of Two Cases and a Narrative Review of the Literature
Authors: Gattringer Michael , Schalamon Georg , Pichler Hannes , Breulmann Franziska Lioba , Buerger Heinz , Mattiassich Georg , Bischofreiter Martin
Published: August 2023

Proximal hamstring tears are among the most common injuries afflicting athletes and middle-aged individuals. Sciatic nerve compression after a proximal hamstring injury, which can occur due to scar formation and subsequent irritation or compression of the nerve, is an infrequent but severe complication with few cases documented in the literature. No evidence is available about the optimal treatment for sciatic nerve symptoms after proximal hamstring injuries. In this case report, we present two cases involving patients primarily treated conservatively at another institution after suffering from a proximal hamstring injury and developing sciatic nerve symptoms over the course of a few months. Both were treated with open neurolysis at our institution without reattachment of the ruptured muscles to the ischial tuberosity due to the chronicity of the injuries. Both patients exhibited neurological symptoms over two years, which recovered after surgery. These two cases show that neurolysis of the sciatic nerve without reattachment of the proximal hamstring muscles is an applicable option for the treatment of chronic proximal hamstring tears with sciatic nerve compression. Further studies will be needed to validate this hypothesis.
Waste Collection Optimisation: A Path to a Green and Sustainable City of Makkah
Authors: Algethami Haneen , Alhothali Ghada Talat
Published: August 2023

Background: Saudi Arabia is a leading country endorsing a sustainable future, from policymaking and investment to infrastructure development. One of the rising concerns in Saudi Arabia's Vision 2030 is solid waste management, especially in Makkah. The Solid Waste Collection Problem (SWCP) refers to the route optimisation of waste collection trucks visiting containers across various locations. Manually generated routes might contain some mistakes, and constructing and revising designed solutions can take a long time. Thus, there is a need to find optimal and fast solutions to this problem. Solving this problem demands tackling numerous routing constraints while aiming to minimise the operational cost. Since solid waste has a significant impact on the environment, reducing fuel consumption must be an objective. Methods: Thus, a mixed-integer programming model is proposed in this paper while using the time-oriented nearest neighbour heuristic. The goal is to investigate their performance on nine existing instances of SWCP in the city of Makkah. The proposed model is implemented in the Gurobi solver. The time-oriented nearest neighbour heuristic constructs the initial solution and is then re-optimised using Google OR-tools. Results: Using the greedy method to construct a solution for this problem generated better solutions when compared to the results obtained without the greedy method. Computational times are also improved by 55.7% on the problem instances. Conclusions: The findings confirm the competitive performance of the proposed method in terms of computational times and solution quality.
Enhanced Mechanical Properties of Al2O3 Nanoceramics via Low Temperature Spark Plasma Sintering of Amorphous Powders
Authors: Zhang Dongjiang , Yu Rui , Feng Xuelei , Guo Xuncheng , Yang Yongkang , Xu Xiqing
Published: August 2023

In this work, Al2O3 nanoceramics were prepared by spark plasma sintering of amorphous powders and polycrystalline powders with similar particle sizes. Effective comparisons of sintering processes and ultimate products depending on starting powder conditions were explored. To ensure near-full density higher than 98% of the Al2O3 nanoceramics, the threshold temperature in SPS is 1450 °C for polycrystalline Al2O3 powders and 1300 °C for amorphous powders. The low SPS temperature for amorphous powders is attributed to the metastable state with high free energy of amorphous powders. The Al2O3 nanoceramics prepared by amorphous powders display a mean grain size of 170 nm, and superior mechanical properties, including high bending strength of 870 MPa, Vickers hardness of 20.5 GPa and fracture toughness of 4.3 MPa∙m1/2. Furthermore, the Al2O3 nanoceramics prepared by amorphous powders showed a larger dynamic strength and dynamic strain. The toughening mechanism with predominant transgranular fracture is explained based on the separation of quasi-boundaries.
Effect of Cutting Surface Integrity on Fatigue Properties of TC17 Titanium Alloy
Authors: Wang Dan , Chen Xiyu , Lai Xunqing , Zhao Guolong , Yang Yinfei
Published: August 2023

The turning process of titanium alloy material will affect the surface structure of the material and lead to a change in its service life. In this paper, the fatigue behavior of the TC17 titanium alloy turning sample was studied through the bending fatigue test. The fatigue life variation rule under the action of thermal coupling was then discussed. This revealed the fatigue fracture mechanism of TC17; the cracks originated from the surface of the source region, and the transient fault region was a ductile fracture. The mathematical model of turning parameters and surface integrity (roughness, microhardness and residual stress) was established, and the influence of turning parameters on fatigue life was analyzed with a mathematical relationship. Drawing a conclusion, the effects of turning parameters on fatigue life at normal temperature are as follows: Feed > Cutting depth > Cutting speed. The fatigue life of vc = 30 m/min, f = 0.25 mm/r, ap = 0.3 mm is only 40,586 cycles per week, the fatigue life of vc = 30 m/min, f = 0.05 mm/r, ap = 0.1 mm has 539,400 cycles per week, that is, the longest fatigue life is 16.6 times the smallest. Small cutting speed, feed, and large cut depth can be chosen based on ensuring practical processing efficiency. The fatigue fracture of the TC17 sample occurred after a certain cycle, and the fatigue fracture mechanism was revealed in this paper.
Investigation on Buckling Performance of Prefabricated Light Steel Frame Materials under the Action of Random Defects during Construction
Authors: Yao Gang , Chen Yuxiao , Yang Yang , Ma Xinlong , Men Wulei
Published: August 2023

This investigation proposes an analytical approach for analyzing the impact of random defects on light steel frame materials. The addition of random defects for the overall and the component units was achieved by integrating Matlab R2022a and Ansys R19.0 finite element software. Nonlinear analysis was conducted to calculate ultimate load factors and nodal ultimate displacements of the materials under various random defects at each stage of construction. A two-factor analysis was employed to investigate the effects of random defects on the calculation results during different construction stages. The investigation reveals that the response of the light steel frame materials to initial defects is more pronounced during the construction stage. Moreover, the construction stage is the main factor that affects the ultimate load factor and nodal ultimate displacement, compared with random defects. The influence of different random defects on structural displacements varies significantly. The displacement development of the light steel frame materials under the influence of component unit defects tends to be more rapid than that of the overall defects. However, their buckling critical loads are essentially similar.
Digital Microfluidic Multiplex RT-qPCR for SARS-CoV-2 Detection and Variants Discrimination
Authors: Ho Kuan-Lun , Ding Jing , Fan Jia-Shao , Tsui Wai Ning Tiffany , Bai Jianfa , Fan Shih-Kang
Published: August 2023

Continuous mutations have occurred in the genome of the SARS-CoV-2 virus since the onset of the COVID-19 pandemic. The increased transmissibility of the mutated viruses has not only imposed medical burdens but also prolonged the duration of the pandemic. A point-of-care (POC) platform that provides multitarget detection will help to track and reduce disease transmissions. Here we detected and discriminated three genotypes of SARS-CoV-2, including the wildtype and two variants of concern (VOCs), the Delta variant and Omicron variant, through reverse transcription quantitative polymerase chain reaction (RT-qPCR) on a digital microfluidics (DMF)-based cartridge. Upon evaluating with the RNA samples of Omicron variant, the DMF RT-qPCR presented a sensitivity of 10 copies/μL and an amplification efficiency of 96.1%, capable for clinical diagnosis. When spiking with SARS-CoV-2 RNA (wildtype, Delta variant, or Omicron variant) and 18S rDNA, the clinical analog samples demonstrated accurate detection and discrimination of different SARS-CoV-2 strains in 49 min.
Modelling and Simulating the Digital Measuring Twin Based on CMM
Authors: Marjanovic Miladin A. , Stojadinovic Slavenko M. , Zivanovic Sasa T.
Published: August 2023

In order to perform the inspection planning process on the coordinate measuring machine (CMM), it is necessary to model the measuring system with workpiece, CMM and fixture. The metrological analysis of the workpiece is then conducted, followed by the creation of a measurement program for simulation on a virtual measuring machine in a CAD environment. This paper presents the modelling and simulation of a virtual measuring system based on a real CMM using PTC Creo Parametric 5.0 software. The simulation involved programming the measuring path and generating a DMIS (*.ncl) file, which represents the standard modelled types of tolerance. The analysis of the metrology of the measuring part for the given forms of tolerance (location, perpendicularity, flatness, etc.) was performed. The components of the CMM and the assembly with defined kinematic connections are also modelled. Following the simulation and generation of the output DMIS file in PTC Creo using the virtual CMM, the real CMM was programmed and used for actual measurements. Subsequently, a measurement report was generated. The main result of this paper is the modelling of an offline Digital Measuring Twin (DMT) based on the DMIS file.
Plant-Based Diets: A Path to Ending CVD as We Know It?
Authors: Najjar Rami Salim , Gewirtz Andrew T.
Published: August 2023

Cardiovascular disease (CVD) is the leading cause of death in the United States, with roughly 700,000 CVD deaths every year [1]. [...]
Potential Epigenetic Effects of Human Milk on Infants’ Neurodevelopment
Authors: Gialeli Giannoula , Panagopoulou Ourania , Liosis Georgios , Siahanidou Tania
Published: August 2023

The advantages of human milk feeding, especially in preterm babies, are well recognized. Infants’ feeding with breast milk lowers the likelihood of developing a diverse range of non-communicable diseases later in life and it is also associated with improved neurodevelopmental outcomes. Although the precise mechanisms through which human milk feeding is linked with infants’ neurodevelopment are still unknown, potential epigenetic effects of breast milk through its bioactive components, including non-coding RNAs, stem cells and microbiome, could at least partly explain this association. Micro- and long-non-coding RNAs, enclosed in milk exosomes, as well as breast milk stem cells, survive digestion, reach the circulation and can cross the blood–brain barrier. Certain non-coding RNAs potentially regulate genes implicated in brain development and function, whereas nestin-positive stem cells can possibly differentiate into neural cells or/and act as epigenetic regulators in the brain. Furthermore, breast milk microbiota contributes to the establishment of infant’s gut microbiome, which is implicated in brain development via epigenetic modifications and key molecules’ regulation. This narrative review provides an updated analysis of the relationship between breast milk feeding and infants’ neurodevelopment via epigenetics, pointing out how breast milk’s bioactive components could have an impact on the neurodevelopment of both full-term and preterm babies.
Nutritional Risk and Sarcopenia Features in Patients with Crohn’s Disease: Relation to Body Composition, Physical Performance, Nutritional Questionnaires and Biomarkers
Authors: Papadimitriou Konstantinos , Detopoulou Paraskevi , Soufleris Konstantinos , Voulgaridou Gavriela , Tsoumana Despoina , Ntopromireskou Panagiotis , Giaginis Constantinos , Chatziprodromidou Ioanna P. , Spanoudaki Maria , Papadopoulou Sousana K.
Published: August 2023

Patients with Crohn’s disease (CD) face malnutrition risk, which, combined with inflammation, can lead to sarcopenia, associated with a worse prognosis. The purpose of the present study was to assess malnutrition and sarcopenia in patients with CD. Fifty-three patients (26 women) participated (38.1 ± 10.9 years, 79% in remission). Body composition, physical performance, nutritional questionnaires, and biomarkers were performed. Malnutrition was screened with the Mini Nutritional Assessment (MNA) and the Malnutrition Inflammation Risk Tool (MIRT) and was assessed with the Global Leadership Initiative on Malnutrition (GLIM) tool using etiologic along with three different phenotypic criteria: low Body Mass Index (BMI), low Calf Circumference (CC), and low Fat-Free Mass Index (FFMI). To find cases and evaluate sarcopenia, the Sarcopenia Questionnaire (SARC-F) and European Working Group on Sarcopenia2 (EWGSOP2) criteria were used. Malnutrition rates were 11.3% (n = 6), 7.5% (n = 4), and 5.6% (n = 3) based on low FFMI, CC, and BMI, correspondingly. Four (7%) patients had low Hand-Grip Strength (HGS), n = 8 (14.8%) had low Appendicular Lean Mass (ALM), and n = 3 (5.6%) had low gait speed. No-one had sarcopenia. A high albumin and triceps skinfold pattern, identified by principal component analysis, was related to reduced C-Reactive Protein (CRP) levels (B = −0.180, SE = 0.085, p = 0.045). In conclusion, based on the studied anthropometric, nutritional, and functional variables, CD patients were not diagnosed with sarcopenia in the present study. Body composition patterns were related to the inflammatory burden, underlying the interplay of inflammation and malnutrition, even in remission states. Further studies on older populations and during disease exacerbation are necessary to explore the potential link between CD, inflammation, and sarcopenia.
Parents’ Diet Quality and Physical Activity Are Associated with Lifestyle in Spanish Children and Adolescents: The PASOS Study
Authors: Monserrat-Mesquida Margalida , Ródenas-Munar Marina , Gómez Santiago F. , Wärnberg Julia , Medrano María , González-Gross Marcela , Gusi Narcís , Aznar Susana , Marín-Cascales Elena , González-Valeiro Miguel A. , Serra-Majem Lluís , Pulgar Susana , Segu Marta , Fitó Montse , Según Genís , Benavente-Marín Juan Carlos , Labayen Idoia , Zapico Augusto G. , Sánchez-Gómez Jesús , Jiménez-Zazo Fabio , Alcaraz Pedro E. , Sevilla-Sánchez Marta , Herrera-Ramos Estefanía , Schröder Helmut , Tur Josep A. , Bouzas Cristina
Published: August 2023

Background: Non-communicable chronic diseases are associated with a low-quality diet, low physical activity, and sedentary behavior. Objective: To assess how parents’ diet and physical activity habits were associated with their offsprings’ lifestyles. Study design: A cross-sectional analysis of 8–16-year-old children and adolescents (n = 2539; 51.9% girls) was carried out within the frame of the first edition of the Physical Activity, Sedentarism, Lifestyles, and Obesity in Spanish Youth study (PASOS-2019). Data on adherence to the Mediterranean Diet (MedDiet), daily moderate–vigorous physical activity (MVPA), and screen time per day (television, computer, video games, and mobile phone) were collected from children and adolescents, and data on parents’ diet quality and physical activity were compiled. Logistic regression models were used to assess the association between parents’ lifestyles and those of children and adolescents. Results: High diet quality of parents was associated with higher adherence to the MedDiet of children and adolescents, as well as high consumption of fruit, vegetables, fish, nuts, and legumes. The high physical activity level of parents was associated with the low consumption of fast foods, sweets, and candies in children and adolescents. Children with high levels of physical activity were those whose parents showed better diet quality and physical activity levels. Conclusions: Parents’ high diet quality and physical activity were associated with healthy lifestyles, higher adherence to the MedDiet, and physical activity of their offspring, mainly in adolescents.
Formulation and Evaluation of Plumbagin-Loaded Niosomes for an Antidiabetic Study: Optimization and In Vitro Evaluation
Authors: Tyagi Rama , Waheed Ayesha , Kumar Neeraj , Ahad Abdul , Bin Jardan Yousef A. , Mujeeb Mohd. , Kumar Ashok , Naved Tanveer , Madan Swati
Published: August 2023

Diabetes treatment requires focused administration with quality systemic circulation to determine the optimal therapeutic window. Intestinal distribution through oral administration with nanoformulation provides several benefits. Therefore, the purpose of this study is to create plumbagin enclosed within niosomes using the quality by design (QbD) strategy for efficient penetration and increased bioavailability. The formulation and optimization of plumbagin-loaded niosomes (P-Ns-Opt) involved the use of a Box–Behnken Design. The particle size (PDI) and entrapment efficiency of the optimized P-Ns-Opt were 133.6 nm, 0.150, and 75.6%, respectively. TEM, DSC, and FTIR were used to analyze the morphology and compatibility of the optimized P-Ns-Opt. Studies conducted in vitro revealed a controlled release system. P-Ns-Opt’s antioxidant activity, α-amylase, and α-glucosidase were evaluated, and the results revealed a dose-dependent efficacy with 60.68 ± 0.02%,90.69 ± 2.9%, and 88.43 ± 0.89%, respectively. In summary, the created P-Ns-Opt demonstrate remarkable potential for antidiabetic activity by inhibiting oxygen radicals, α-amylase, and α-glucosidase enzymes and are, therefore, a promising drug delivery nanocarrier in the management and treatment of diabetes.
Taste-Masked Flucloxacillin Powder Part 1: Optimisation of Fabrication Process Using a Mixture Design Approach
Authors: Yoo Okhee , Salman Sam , von Ungern-Sternberg Britta S. , Lim Lee Yong
Published: August 2023

It is extremely challenging to formulate age-appropriate flucloxacillin medicines for young children, because flucloxacillin sodium (FS) has a lingering, highly bitter taste, dissolves quickly in saliva, and requires multiple daily dosing at relatively large doses for treating skin infections. In this paper, we describe a promising taste-masked flucloxacillin ternary microparticle (FTM) formulation comprising FS, Eudragit EPO (EE), and palmitic acid (PA). To preserve the stability of the thermolabile and readily hydrolysed flucloxacillin, the fabrication process employed a non-aqueous solvent evaporation method at ambient temperature. Optimisation of the fabrication method using a mixture design approach resulted in a robust technique that generated stable and reproducible FTM products. The optimised method utilised only a single solvent evaporation step and minimal amounts of ICH class III solvents. It involved mixing two solution phases—FS dissolved in ethanol:acetone (1:4 v/v), and a combination of EE and PA dissolved in 100% ethanol—to give a ternary FS:EE:PA system in ethanol: acetone (3:1 v/v). Solvent evaporation yielded the FTMs containing an equimolar ratio of FS:EE:PA (1:0.8:0.6 w/w). The fabrication process, after optimisation, demonstrated robustness, reproducibility, and potential scalability.
Advancing Treatment Strategies: A Comprehensive Review of Drug Delivery Innovations for Chronic Inflammatory Respiratory Diseases
Authors: Wang Junming , Wang Pengfei , Shao Yiru , He Daikun
Published: August 2023

Chronic inflammatory respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, present ongoing challenges in terms of effective treatment and management. These diseases are characterized by persistent inflammation in the airways, leading to structural changes and compromised lung function. There are several treatments available for them, such as bronchodilators, immunomodulators, and oxygen therapy. However, there are still some shortcomings in the effectiveness and side effects of drugs. To achieve optimal therapeutic outcomes while minimizing systemic side effects, targeted therapies and precise drug delivery systems are crucial to the management of these diseases. This comprehensive review focuses on the role of drug delivery systems in chronic inflammatory respiratory diseases, particularly nanoparticle-based drug delivery systems, inhaled corticosteroids (ICSs), novel biologicals, gene therapy, and personalized medicine. By examining the latest advancements and strategies in these areas, we aim to provide a thorough understanding of the current landscape and future prospects for improving treatment outcomes in these challenging conditions.
Analysis and Prediction of Image Quality Degradation Caused by Diffraction of Infrared Optical System Turning Marks
Authors: Ye Haokun , Zhang Jianping , Zhao Shangnan , Liu Mingxin , Zhang Xin
Published: August 2023

This paper addresses the issue of reduced image quality due to annular turning marks formed by single-point diamond turning (SPDT) during the processing of metal-based mirrors and infrared lenses. An ideal single-point diamond turning marks diffraction action model to quantitatively analyze the impact of turning marks diffraction on imaging quality degradation is proposed. Based on this model, a fast estimation algorithm for the optical modulation transfer function of the system under turning marks diffraction (TMTF) is proposed. The results show that the TMTF algorithm achieves high computational accuracy, with a relative error of only 3% in diffraction efficiency, while being hundreds of times faster than rigorous coupled wave analysis (RCWA). This method is significant for reducing manufacturing costs and improving production efficiency, as it avoids the problem of being unable to compute large-size optical systems due to computational resource and time constraints.
Simple Method of Light Field Calculation for Shaping of 3D Light Curves
Authors: Khonina Svetlana N. , Porfirev Alexey P. , Volotovskiy Sergey G. , Ustinov Andrey V. , Karpeev Sergey V.
Published: August 2023

We propose a method for generating three-dimensional light fields with given intensity and phase distributions using purely phase transmission functions. The method is based on a generalization of the well-known approach to the design of diffractive optical elements that focus an incident laser beam into an array of light spots in space. To calculate purely phase transmission functions, we use amplitude encoding, which made it possible to implement the designed elements using a single spatial light modulator. The generation of light beams in the form of rings, spirals, Lissajous figures, and multi-petal “rose” distributions uniformly elongated along the optical axis in the required segment is demonstrated. It is also possible to control the three-dimensional structure of the intensity and phase of the shaped light fields along the propagation axis. The experimentally generated intensity distributions are in good agreement with the numerically obtained results and show high potential for the application of the proposed method in laser manipulation with nano- and microparticles, as well as in laser material processing.