bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD
Authors: Vitulo Manuela , Gnodi Elisa , Rosini Giulia , Meneveri Raffaella , Giovannoni Roberto , Barisani Donatella
Published: August 2023

Nonalcoholic fatty liver disease (NAFLD, including nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH)) is a high-prevalence disorder, affecting about 1 billion people, which can evolve to more severe conditions like cirrhosis or hepatocellular carcinoma. NAFLD is often concomitant with conditions of the metabolic syndrome, such as central obesity and insulin-resistance, but a specific drug able to revert NAFL and prevent its evolution towards NASH is still lacking. With the liver being a key organ in metabolic processes, the potential therapeutic strategies are many, and range from directly targeting the lipid metabolism to the prevention of tissue inflammation. However, side effects have been reported for the drugs tested up to now. In this review, different approaches to the treatment of NAFLD are presented, including newer therapies and ongoing clinical trials. Particular focus is placed on the reverse cholesterol transport system and on the agonists for nuclear factors like PPAR and FXR, but also drugs initially developed for other conditions such as incretins and thyromimetics along with validated natural compounds that have anti-inflammatory potential. This work provides an overview of the different therapeutic strategies currently being tested for NAFLD, other than, or along with, the recommendation of weight loss.
The Effect of Aging on Nitric Oxide Production during Cerebral Ischemia and Reperfusion in Wistar Rats and Spontaneous Hypertensive Rats: An In Vivo Microdialysis Study
Authors: Ito Yasuo , Nagoya Harumitsu , Yamazato Masamizu , Asano Yoshio , Sawada Masahiko , Shimazu Tomokazu , Hirayama Makiko , Yamamoto Toshimasa , Araki Nobuo
Published: August 2023

Nitric oxide (NO) is involved in the pathogenesis of cerebral ischemic injury. Here, we investigated the effects of aging on NO production during cerebral ischemia-reperfusion (IR). Male Wister rats (WRs) were assigned to 12-month-old (older; n = 5) and 3-month-old (younger; n = 7) groups. Similarly, male spontaneous hypertensive rats (SHRs) were allocated to 12-month-old (older; n = 6) and 3-month-old (younger; n = 8) groups. After anesthesia, their NO production was monitored using in vivo microdialysis probes inserted into the left striatum and hippocampus. Forebrain cerebral IR injuries were produced via ligation of the bilateral common carotid arteries, followed by reperfusion. The change in the NO3− of the older rats in the SHR groups in the striatum was less compared to that of the younger rats before ischemia, during ischemia, and after reperfusion (p < 0.05). In the hippocampus, the change in the NO3− of the older rats in the SHR groups was lower compared to that of the younger rats after reperfusion (p < 0.05). There were no significant differences between the two WR groups. Our findings suggested that aging in SHRs affected NO production, especially in the striatum, before and during cerebral ischemia, and after reperfusion. Hypertension and aging may be important factors impacting NO production in brain IR injury.
KRAS Mutation Status in Bulgarian Patients with Advanced and Metastatic Colorectal Cancer
Authors: Radanova Maria , Mihaylova Galya , Stoyanov George St. , Draganova Vyara , Zlatarov Aleksandar , Kolev Nikola , Dimitrova Eleonora , Conev Nikolay , Ivanova Diana
Published: August 2023

RAS somatic variants are predictors of resistance to anti-EGFR therapy for colorectal cancer (CRC) and affect the outcome of the disease. Our study aimed to evaluate the frequency of RAS, with a focus on KRAS variants, and their association with tumor location and some clinicopathological characteristics in Bulgarian CRC patients. We prospectively investigated 236 patients with advanced and metastatic CRC. Genomic DNA was extracted from FFPE tumor tissue samples, and commercially available kits were used to detect RAS gene somatic mutations via real-time PCR. A total of 115 (48.73%) patients tested positive for RAS mutations, with 106 (44.92%) testing positive for KRAS mutations. The most common mutation in exon 2 was c.35G>T p.Gly12Val (32.56%). We did not find a significant difference in KRAS mutation frequency according to tumor location. However, patients with a mutation in exon 4 of KRAS were 3.23 times more likely to have a tumor in the rectum than in other locations (95% CI: 1.19–8.72, p = 0.021). Studying the link between tumor location and KRAS mutations in exon 4 is crucial for better characterizing CRC patients. Further research with larger cohorts, especially in rectal cancer patients, could provide valuable insights for patient follow-up and treatment selection.
Molecular Mechanisms Underlying Vascular Liver Diseases: Focus on Thrombosis
Authors: Giuli Lucia , Pallozzi Maria , Venturini Giulia , Gasbarrini Antonio , Ponziani Francesca Romana , Santopaolo Francesco
Published: August 2023

Vascular liver disorders (VLDs) comprise a wide spectrum of clinical-pathological entities that primarily affect the hepatic vascular system of both cirrhotic and non-cirrhotic patients. VLDs more frequently involve the portal and the hepatic veins, as well as liver sinusoids, resulting in an imbalance of liver homeostasis with serious consequences, such as the development of portal hypertension and liver fibrosis. Surprisingly, many VLDs are characterized by a prothrombotic phenotype. The molecular mechanisms that cause thrombosis in VLD are only partially explained by the alteration in the Virchow’s triad (hypercoagulability, blood stasis, and endothelial damage) and nowadays their pathogenesis is incompletely described and understood. Studies about this topic have been hampered by the low incidence of VLDs in the general population and by the absence of suitable animal models. Recently, the role of coagulation imbalance in liver disease has been postulated as one of the main mechanisms linked to fibrogenesis, so a novel interest in vascular alterations of the liver has been renewed. This review provides a detailed analysis of the current knowledge of molecular mechanisms of VLD. We also focus on the promising role of anticoagulation as a strategy to prevent liver complications and to improve the outcome of these patients.
Increased Expression of miR-223-3p and miR-375-3p and Anti-Inflammatory Activity in HDL of Newly Diagnosed Women in Advanced Stages of Breast Cancer
Authors: Santana Monique de Fatima Mello , Sawada Maria Isabela Bloise Alves Caldas , Santos Aritania Sousa , Reis Mozania , Xavier Jacira , Côrrea-Giannella Maria Lúcia , Hirata Andrea Harumy de Lima , Gebrim Luiz Henrique , Soriano Francisco Garcia , Camacho Cleber Pinto , Passarelli Marisa
Published: August 2023

The expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naïve of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology.
Biopolymers in Drug and Gene Delivery Systems
Authors: Skorik Yury A.
Published: August 2023

Recent years have seen remarkable advances in the field of drug and gene delivery systems, revolutionizing the way we approach therapeutic treatments [...]
The Interplay of Sulfur and Selenium Enabling Variations in Micronutrient Accumulation in Red Spinach
Authors: Saeed Kashif , Nisa Fatiha Kalam , Abdalla Muna Ali , Mühling Karl Hermann
Published: August 2023

Aside from its importance in human and animal health, low levels of foliar-applied selenate (SeO4) can be advantageous in the presence of sulfur (S), contributing to improved growth, nutrient uptake, and crop quality. A hydroponic experiment in a growth chamber explored the interactive influence of Se and S on micronutrients and several quality indices, such as soluble sugars, organic acids, and total protein concentrations in spinach (Spinacia oleracea L.). Three levels of S (deprivation, adequate, and excessive) with varying quantities of Se (deficient, moderate, and higher) were examined in combination. Under S starvation and along with S nourishment in plant parts, Se treatments were found to cause noticeable variations in plant biomass and the concentrations of the examined elements and other quality parameters. Both Se levels promoted S accumulation in S-treated plants. Although the Se treatment had the opposite effect in shoots, it had a favorable impact on minerals (apart from Mn) in roots grown under S-limiting conditions. The S and Se relationship highlighted beneficial and/or synergistic effects for Mn and Fe in edible spinach portions. Reducing sugars were synergistically boosted by adequate S and moderate Se levels in roots, while in shoots, they were accumulated under moderate-or-higher Se and excessive S. Furthermore, the concentration of the quantified organic acids under S-deficient conditions was aided by various Se levels. In roots, moderate Se under high S application enhanced both malic acid and citric acid, while in the edible parts, higher Se under both adequate and elevated S levels were found to be advantageous in malic acid accumulation. Moreover, by elevating S levels in plant tissues, total protein concentration increased, whereas both moderate and high Se levels (Se1 and Se2) did not alter total protein accumulation in high S-applied roots and shoots. Our findings show that the high S and medium Se dose together benefit nutrient uptake; additionally, their combinations support soluble sugars and organic acids accumulation, contributing ultimately to the nutritional quality of spinach plants. Moreover, consuming 100 g of fresh red spinach shoot enriched with different Se and S levels can contribute to humans’ daily micronutrients intake.
MiRNA-146a—A Key Player in Immunity and Diseases
Authors: Gilyazova Irina , Asadullina Dilara , Kagirova Evelina , Sikka Ruhi , Mustafin Artur , Ivanova Elizaveta , Bakhtiyarova Ksenia , Gilyazova Gulshat , Gupta Saurabh , Khusnutdinova Elza , Gupta Himanshu , Pavlov Valentin
Published: August 2023

miRNA-146a, a single-stranded, non-coding RNA molecule, has emerged as a valuable diagnostic and prognostic biomarker for numerous pathological conditions. Its primary function lies in regulating inflammatory processes, haemopoiesis, allergic responses, and other key aspects of the innate immune system. Several studies have indicated that polymorphisms in miRNA-146a can influence the pathogenesis of various human diseases, including autoimmune disorders and cancer. One of the key mechanisms by which miRNA-146a exerts its effects is by controlling the expression of certain proteins involved in critical pathways. It can modulate the activity of interleukin-1 receptor-associated kinase, IRAK1, IRAK2 adaptor proteins, and tumour necrosis factor (TNF) targeting protein receptor 6, which is a regulator of the TNF signalling pathway. In addition, miRNA-146a affects gene expression through multiple signalling pathways, such as TNF, NF-κB and MEK-1/2, and JNK-1/2. Studies have been carried out to determine the effect of miRNA-146a on cancer pathogenesis, revealing its involvement in the synthesis of stem cells, which contributes to tumourigenesis. In this review, we focus on recent discoveries that highlight the significant role played by miRNA-146a in regulating various defence mechanisms and oncogenesis. The aim of this review article is to systematically examine miRNA-146a’s impact on the control of signalling pathways involved in oncopathology, immune system development, and the corresponding response to therapy.
Analysis of Predicted Amino Acid Sequences of Diatom Microtubule Center Components
Authors: Petrova Darya P. , Morozov Alexey A. , Potapova Nadezhda A. , Bedoshvili Yekaterina D.
Published: August 2023

Diatoms synthesize species-specific exoskeletons inside cells under the control of the cytoskeleton and microtubule center. Previous studies have been conducted with the visualization of the microtubule center; however, its composition has not been studied and reliably established. In the present study, several components of MTOC in diatoms, GCP (gamma complex proteins), Aurora A, and centrins have been identified. Analysis of the predicted amino acid sequences of these proteins revealed structural features typical for diatoms. We analyzed the conserved amino acids and the motives necessary for the functioning of proteins. Phylogenetic analysis of GCP showed that all major groups of diatoms are distributed over phylogenetic trees according to their systematic position. This work is a theoretical study; however, it allows drawing some conclusions about the functioning of the studied components and possible ways to regulate them.
Selection Behavior and OBP-Transcription Response of Western Flower Thrips, Frankliniella occidentalis, to Six Plant VOCs from Kidney Beans
Authors: Wang Yanhui , Zhu Xiaobing , Jin Yixuan , Duan Ruichuan , Gu Yunkai , Liu Xiaowei , Qian Lei , Chen Fajun
Published: August 2023

Plant volatile organic compounds (VOCs) are an important link that mediates chemical communication between plants and plants, plants and insects, and plants and natural enemies of insect pests. In this study, we tested the response in the selective behavior of western flower thrips, Frankliniella occidentalis, to the VOCs of kidney bean, Phaseolus vulgaris L., to explore their “attraction” or “repellent” effects regarding their application in integrated pest management (i.e., IPM). The results indicated that 12.7 μL/mL (E, E, E, E)-squalene, 3.2 μL/mL dioctyl phthalate, and 82.2 μL/mL ethyl benzene had a significantly attractive effect on the selective behavior of F. occidentalis, while 10.7 μL/mL and 21.4 μL/mL 2,6-ditert-butyl-4-methyl phenol had a significantly repulsive effect on the selective behavior of F. occidentalis, showing that F. occidentalis responds differently to specific concentrations of VOCs from P. vulgaris plant emissions. Interestingly, the three compounds with the specific above concentrations, after being mixed in pairs, significantly attracted F. occidentalis compared to the control treatment; however, the mixture with the three above compounds had no significant different effect on F. occidentalis compared to the control treatment. It can be seen that the effect with the mixtures of three kinds of VOCs had the same function and may not get better. Simultaneously, the reasons for this result from the transcription levels of odorant-binding protein genes (OBPs) were determined. There were differences in the types and transcription levels of OBPs, which played a major role in the host selection behavior of F. occidentalis under the mixed treatment of different VOCs. It is presumed that there are specific VOCs from P. vulgaris plants that have a good repellent or attracting effect on the selective behavior of F. occidentalis, which can be used for the development of plant-derived insect attractants and repellents to serve as IPM in fields. But attention should be paid to the antagonism between plant-derived preparations and VOCs produced by plants themselves after application.
Time- and Gender-Dependent Alterations in Mice during the Aging Process
Authors: Jin Jing , Yang Xiaoquan , Gong Hui , Li Xiangning
Published: August 2023

Compared to young people and adults, there are differences in the ability of elderly people to resist diseases or injuries, with some noticeable features being gender-dependent. However, gender differences in age-related viscera alterations are not clear. To evaluate a potential possibility of gender differences during the natural aging process, we used three age groups to investigate the impact on spleens, kidneys, and adrenal glands. The immunofluorescence results showed that male-specific p21 proteins were concentrated in the renal tubule epithelial cells of the kidney. Histological staining revealed an increase in the frequencies of fat vacuoles located in the renal tubule epithelial cells of the cortex, under the renal capsule in the kidneys of male mice with age. In female mice, we found that the width of the globular zone in the adrenal gland cortex was unchanged with age. On the contrary, the male displayed a reduction in width. Compared to females, the content of epinephrine in adrenal gland tissue according to ELISA analysis was higher in adults, and a greater decline was observed in aged males particularly. These data confirmed the age-dependent differences between female and male mice; therefore, gender should be considered one of the major factors for personalized treatment in clinical diagnosis and treatment.
Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis
Authors: Kraaijvanger Raisa , Ambarus Carmen A. , Damen Jan , van der Vis Joanne J. , Kazemier Karin M. , Grutters Jan C. , van Moorsel Coline H. M. , Veltkamp Marcel
Published: August 2023

The unknown etiology of sarcoidosis, along with the variability in organ involvement and disease course, complicates the effective treatment of this disease. Based on recent studies, the cellular inflammatory pathways involved in granuloma formation are of interest regarding possible new treatment options, such as the mechanistic (formerly mammalian) target of rapamycin complex 1 (mTORC1) pathway, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome pathway. The aim of this study was to explore the potential coexpression of these three inflammatory pathways in patients with sarcoidosis and see whether possible differences were related to disease outcome. The tissue of 60 patients with sarcoidosis was used to determine the activity of these three signaling pathways using immunohistochemistry. The activation of NLRP3 was present in 85% of all patients, and the activation of mTORC1 and JAK/STAT was present in 49% and 50% of patients, respectively. Furthermore, the presence of NLRP3 activation at diagnosis was associated with a chronic disease course of sarcoidosis. Our finding of different new conceptual inflammatory tissue phenotypes in sarcoidosis could possibly guide future treatment studies using the available inhibitors of either NLRP3, JAK-STAT, and mTORC1 inhibitors in a more personalized medicine approach.
Plasma Bile Acid Profiling and Modulation of Secreted Mucin 5AC in Cholangiocarcinoma
Authors: Danese Elisa , Lievens Patricia M.-J. , Padoan Andrea , Peserico Denise , Galavotti Roberta , Negrini Davide , Gelati Matteo , Conci Simone , Ruzzenente Andrea , Salvagno Gian Luca , Lippi Giuseppe
Published: August 2023

Studies investigating the potential role of circulating bile acids (BAs) as diagnostic biomarkers for cholangiocarcinoma (CCA) are sparse and existing data do not adjust for confounding variables. Furthermore, the mechanism by which BAs affect the expression of the oncogenic mucin 5AC (MUC5AC) has never been investigated. We performed a case–control study to characterise the profile of circulating BAs in patients with CCA (n = 68) and benign biliary disease (BBD, n = 48) with a validated liquid chromatography–tandem mass spectrometry technique. Odd ratios (OR) for CCA associations were calculated with multivariable logistic regression models based on a directed acyclic graph structure learning algorithm. The most promising BAs were then tested in an in vitro study to investigate their interplay in modulating MUC5AC expression. The total concentration of BAs was markedly higher in patients with CCA compared with BBD controls and accompanied by a shift in BAs profile toward a higher proportion of primary conjugated BAs (OR = 1.50, CI: 1.14 to 1.96, p = 0.003), especially taurochenodeoxycholic acid (TCDCA, OR = 42.29, CI: 3.54 to 504.63, p = 0.003) after multiple adjustments. Western blot analysis of secreted MUC5AC in human primary cholangiocytes treated with primary conjugated BAs or with TCDCA alone allowed us to identify a novel 230 kDa isoform, possibly representing a post-translationally modified MUC5AC specie.
Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes
Authors: Franchina Mariausilia , Pizzimenti Cristina , Fiorentino Vincenzo , Martini Maurizio , Ricciardi Giuseppina Rosaria Rita , Silvestris Nicola , Ieni Antonio , Tuccari Giovanni
Published: August 2023

HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, supporting a re-consideration of immunohistochemical negative scores of 0, 1+ and the 2+/in situ hybridization (ISH) negative phenotype. In the present review, we outline the criteria needed to exactly distinguish HER2-low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody–drug conjugates (ADCs) in treating these groups of tumors. In particular, trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC, has been recently approved by the US Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06 trial, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally, we hope that new guidelines may help to codify HER2-low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment.
Proteomic Approach to Anemonia sulcata and Its Symbiont Symbiodinium spp. as New Source of Potential Biotechnological Applications and Climate Change Biomarkers
Authors: Melendez-Perez Ana Maria , Escobar Niño Almudena , Carrasco-Reinado Rafael , Martin Diaz Laura , Fernandez-Acero Francisco Javier
Published: August 2023

Marine ecosystems are among the richest in terms of biodiversity, and at present, still remain largely unknown today. In the molecular biology era, several analyses have been conducted to unravel the biological processes in this ecosystem. These systems have provided biotechnological solutions to current problems, including the treatment of diseases, as well as for the development of new biotechnological tools with applications in biomedicine and/or agri-food. In addition, in the context of climate change and global warming, these studies become even more necessary for the development of molecular tools that allow a reliable follow-up of this situation to anticipate alterations and responses of bioindicator species and to create a database to prevent and predict the environmental and climatic changes before the damage is irreversible. Proteomics approaches have revealed their potential use to obtain the set of biological effectors that lead to the real biological station on a specific stage, the proteins. In addition, proteomics-based algorithms have allowed the discovery of proteins with new potential biotechnological applications from proteome data through “applied proteomics”. In this project, the first proteome analysis of the sea anemone, Anemonia sulcata, and its symbiont has been developed. These organisms present a wide distribution sea ecosystem. In Spain, it is accepted as a fishing and aquaculture species. Moreover, Anemonia sulcate has a symbiotic relation with autotroph Dinoflagellates, Symbiodinium spp., that allows the study of its relation at the molecular level. For the first characterization of A. sulcata proteome, three independent biological replicates were used, and proteins were extracted and analyzed by LC–MS/MS, allowing the quantification of 325 proteins, 81 from Symbiodinium spp. proteins and 244 from A. sulcata proteins. These proteins were subjected to gene ontology categorization by Cellular Component, Molecular Function and Biological Process. These analyzes have allowed the identification of biomarkers of gene expression as potential powerful emerging diagnostic tools to identify and characterize the molecular drivers of climate change stresses and improve monitoring techniques. In addition, through the application of novel algorithms for the detection of bioactive compounds based on the analysis of molecules of marine origin, the proteome has allowed the identification of proteins with potential applications in the fields of biomedicine and agri-food.
Image Encryption Algorithm Using Multi-Level Permutation and Improved Logistic–Chebyshev Coupled Map
Authors: Jiang Mingfang , Yang Hengfu
Published: August 2023

To improve the randomness of the Chebyshev chaotic sequences by coupling the Logistic map and the Chebyshev map, a new one-dimensional Logistic–Chebyshev chaotic map (LCCM) is first presented in this paper. Several tests, including the bifurcation diagram, Lyapunov exponents, and information entropy, are employed to analyze the dynamics of the LCCM. The proposed LCCM has better ergodicity and unpredictability than the traditional Chebyshev map. Next, a new image encryption algorithm based on the LCCM and multi-level manipulation is proposed. The LCCM is used to control the pixel permutation, bit-level shuffling, and subsequent pixel diffusion based on the modulo and XOR operation. Extensive experiments, including histogram analysis, information entropy, adjacent pixel correlation, and key sensitivity, show that the image encryption algorithm has high security and can effectively resist malicious attacks.
Assessing the Security and Privacy of Android Official ID Wallet Apps
Authors: Kouliaridis Vasileios , Karopoulos Georgios , Kambourakis Georgios
Published: August 2023

With the increasing use of smartphones for a wide variety of online services, states and countries are issuing official applications to store government-issued documents that can be used for identification (e.g., electronic identity cards), health (e.g., vaccination certificates), and transport (e.g., driver’s licenses). However, the privacy and security risks associated with the storage of sensitive personal information on such apps are a major concern. This work presents a thorough analysis of official Android wallet apps, focusing mainly on apps used to store identification documents and/or driver’s licenses. Specifically, we examine the security and privacy level of such apps using three analysis tools and discuss the key findings and the risks involved. We additionally explore Android app security best practices and various security measures that can be employed to mitigate these risks, such as updating deprecated components and libraries. Altogether, our findings demonstrate that, while there are various security measures available, there is still a need for more comprehensive solutions to address the privacy and security risks associated with the use of Android wallet apps.
A Novel Approach of Resource Allocation for Distributed Digital Twin Shop-Floor
Authors: Zhang Haijun , Yan Qiong , Qin Yan , Chen Shengwei , Zhang Guohui
Published: August 2023

Facing global market competition and supply chain risks, many production companies are leaning towards distributed manufacturing because of their ability to utilize a network of manufacturing resources located around the world. Deriving from information and communication technologies and artificial intelligence, the digital twin shop-floor (DTS) has received great attention from academia and industry. DTS is a virtual shop-floor that is almost identical to the physical shop-floor. Therefore, multiple physical shop-floors located in different places can easily be interconnected to realize a DT that is a distributed digital twin shop-floor (D2TS). However, some challenges still hinder effective and efficient resource allocation among D2TSs. In order to attempt to address the issues, firstly, this paper proposes an information architecture for D2TSs based on cloud–fog computing; secondly, a novel mechanism of D2TS resource allocation (D2TSRA) is designed. The proposed mechanism both makes full use of a digital twin to support dynamic allocation of geographic resources and avoids the centralized solutions of the digital twin which lead to a heavy burden on the network bandwidth; thirdly, the optimization problem in D2TSRA is solved by a BP neural network algorithm and an improved genetic algorithm; fourthly, a case study for distributed collaborative manufacturing of aero-engine casing is employed to validate the effectiveness and efficiency of the proposed method of resource allocation for D2TS; finally, the paper is summarized and the relevant research directions are prospected.
A Service-Efficient Proxy Mobile IPv6 Extension for IoT Domain
Authors: Khan Habib Ullah , Hussain Anwar , Nazir Shah , Ali Farhad , Khan Muhammad Zubair , Ullah Inam
Published: August 2023

The upcoming generation of communications can provide richer mobility, high data rate, reliable security, better quality of services, and supporting mobility requirements in the Internet of Things (IoT) environment. Integrating modern communication with IoT demands more secure, scalable, and resource-efficient mobility solutions for better business opportunities. In a massive 6G-enabled IoT environment, modern mobility solutions such as proxy mobile IPv6 (PMIPv6) have the potential to provide enhanced mobility and resource efficiency. For supporting richer mobility, a cost-effective and resource-efficient mobility solution is required in a massive 6G-enabled IoT environment. The main objective of the presented study is to provide a resource-friendly mobility solution for supporting the effective integration of future communication in the massive IoT domain. In that context, a location-based, resource-efficient PMIPv6 extension protocol is proposed to provide resource efficiency in terms of required signaling, packet loss, and handover latency. To compare and analyze the proposed model’s effectiveness, mathematical equations are derived for the existing as well as for the proposed solution, and such equations are implemented. Based on the comparison among existing and proposed solutions, the results show that the proposed location-based service-oriented proxy mobile IPv6 extension is resource efficient for supporting mobility in 6G-enabled IoT.
Atg2 Regulates Cellular and Humoral Immunity in Drosophila
Authors: Qin Bo , Yu Shichao , Chen Qiming , Jin Li Hua
Published: August 2023

Autophagy is a process that promotes the lysosomal degradation of cytoplasmic proteins and is highly conserved in eukaryotic organisms. Autophagy maintains homeostasis in organisms and regulates multiple developmental processes, and autophagy disruption is related to human diseases. However, the functional roles of autophagy in mediating innate immune responses are largely unknown. In this study, we sought to understand how Atg2, an autophagy-related gene, functions in the innate immunity of Drosophila melanogaster. The results showed that a large number of melanotic nodules were produced upon inhibition of Atg2. In addition, inhibiting Atg2 suppressed the phagocytosis of latex beads, Staphylococcus aureus and Escherichia coli; the proportion of Nimrod C1 (one of the phagocytosis receptors)-positive hemocytes also decreased. Moreover, inhibiting Atg2 altered actin cytoskeleton patterns, showing longer filopodia but with decreased numbers of filopodia. The expression of AMP-encoding genes was altered by inhibiting Atg2. Drosomycin was upregulated, and the transcript levels of Attacin-A, Diptericin and Metchnikowin were decreased. Finally, the above alterations caused by the inhibition of Atg2 prevented flies from resisting invading pathogens, showing that flies with low expression of Atg2 were highly susceptible to Staphylococcus aureus and Erwinia carotovora carotovora 15 infections. In conclusion, Atg2 regulated both cellular and humoral innate immunity in Drosophila. We have identified Atg2 as a crucial regulator in mediating the homeostasis of immunity, which further established the interactions between autophagy and innate immunity.
Development of a Diet Production System for Conopomorpha cramerella (Lepidoptera: Gracillariidae), a Major Cocoa Production Pest in Southeast Asia and the Pacific Islands
Authors: Niogret Jerome , Savantil Anisah Binti , Ekayanti Arni , Jaus Mavis Peter , Wulan Wulan , Mitzo Elviah , Marelli Jean-Philippe , Conlong Desmond
Published: August 2023

The development of artificial diets for the cocoa pod borer Conopomorpha cramerella, a major pest of cocoa plants, has undergone significant advancements. In this study, we present the success rates of two diet formulations, MM1 and MM4, which have been progressively improved. Nutritional composition analysis revealed that the MM1 diet differed from the natural host, cocoa pods, in several aspects, including protein, carbohydrate, and vitamin C content. To address these differences, modifications were made to the diet compositions, leading to the MM4 diet version. These modifications resulted in improved diet quality and reduced contamination, leading to enhanced success rates in all stages of C. cramerella development. Larval development, pupation success rates, and adult emergence rates were significantly higher in the MM4 diet compared with the MM1 diet. Moreover, the duration of larval development and pupal stage decreased, while adult longevity increased with the MM4 diet. The overall development success of diet-reared insects from egg to adult was comparable with that of insects reared on cocoa pods. However, the cocoon formation, body length and fresh weight of the adults reared on the artificial diets were lower than those reared on cocoa pods. This diet formulation provides a promising approach for laboratory rearing of C. cramerella and opens avenues for further research and mass-rearing initiatives to mitigate the impact of this pest on cocoa production.
Development and Validation of Robust Ferroptosis-Related Genes in Myocardial Ischemia-Reperfusion Injury
Authors: Wei Xiuxian , Li Yi , Luo Pengcheng , Dai Yue , Jiang Tao , Xu Mulin , Hao Yi , Zhang Cuntai , Liu Yu
Published: August 2023

(1) Background: Despite the evidence that ferroptosis is involved in myocardial ischemia-reperfusion (MIR), the critical regulator of ferroptosis in MIR remains unclear. (2) Methods: We included three GEO datasets and a set of ferroptosis-related genes with 259 genes. Following the identification of the differentially expressed ferroptosis-related genes (DEFRGs) and hub genes, we performed the functional annotation, protein–protein interaction network, and immune infiltration analysis. The GSE168610 dataset, a cell model, and an animal model were then used to verify key genes. (3) Results: We identified 17 DEFRGs and 9 hub genes in the MIR samples compared to the control. Heme oxygenase 1 (Hmox1), activating transcription factor 3 (Atf3), epidermal growth factor receptor (Egfr), and X-box binding protein 1 (Xbp1) were significantly upregulated in response to ischemic and hypoxic stimuli. In contrast, glutathione peroxidase 4 (Gpx4) and vascular endothelial growth factor A (Vegfa) were consistently decreased in either the oxygen and glucose deprivation/reoxygenation cell or the MIR mouse model. (4) Conclusions: This study emphasized the relevance of ferroptosis in MIR. It has been successfully demonstrated that nine ferroptosis-related genes (Hmox1, Atf3, Egfr, Gpx4, Cd44, Vegfa, asparagine synthetase (Asns), Xbp1, and bromodomain containing 4 (Brd4)) are involved in the process. Additional studies are needed to explore potential therapeutic targets for MIR.
New Perspectives and Strategies for the Management of Hypertension
Authors: Angeli Fabio
Published: August 2023

Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide [...]
Associations between Menopausal Hormone Therapy and Colorectal, Lung, or Melanoma Cancer Recurrence and Mortality: A Narrative Review
Authors: Fiol Gabriel , Lete Iñaki , Nieto Laura , Santaballa Ana , Pla María Jesús , Baquedano Laura , Calaf Joaquín , Coronado Pluvio , de la Viuda Esther , Llaneza Plácido , Otero Borja , Sánchez-Méndez Sonia , Ramírez Isabel , Mendoza Nicolas
Published: August 2023

Objective: to develop eligibility criteria for use in non-gynecological cancer patients. Methods: We searched all the articles published in peer-reviewed journals up to March 2021. We utilized the PICOS standards and the following selection criteria: menopausal women with a history of non-gynecological and non-breast cancer who underwent hormone replacement therapy (HRT) using various preparations (oestrogens alone or in combination with a progestogen, tibolone, or tissue selective oestrogen complex) and different routes of administration (including oral, transdermal, vaginal, or intra-nasal). We focused on randomized controlled trials as well as relevant extension studies or follow-up reports, specifically examining recurrence and mortality outcomes. Results: Women colorectal cancer survivors who use MHT have a lower risk of death from any cause than those survivors who do not use MHT. Women who are skin melanoma survivors using MHT have a longer survival rate than non-MHT survivors. There is no evidence that women lung cancer survivors who use MHT have a different survival rate than those who do not use MHT. Conclusions: MHT is safe for women who have a history of colorectal, lung, or skin melanoma cancers.
Evaluation of Medial Meniscal Extrusion Using Radiography
Authors: Murata Shohei , Kijima Hiroaki , Saito Kimio , Saito Hidetomo , Miura Takanori , Akagawa Manabu , Tsukamoto Hiroaki , Sasaki Kana , Ebina Toshihito , Nozaka Koji , Miyakoshi Naohisa
Published: August 2023

Recently, there has been increasing interest in medial meniscal extrusion (MME), but few reports have evaluated MME via X-ray. In this study, the amount of MME and meniscal height at the medial border of the tibia were measured via X-ray with gradation processing. The extrusion length divided by the meniscal height yields the meniscal extrusion ratio, which was used as an index. In addition, the medial meniscal length of the part protruding from the medial border of the tibia on MRI was measured as an absolute value. Then, the correlation between the meniscal extrusion ratio and the amount of MME on MRI was examined, and there was a strong correlation between the meniscal extrusion ratio via X-ray and the amount of MME on MRI (correlation coefficient 0.860, p < 0.0001). The cut-off value of the meniscal extrusion ratio via X-ray for positive meniscal extrusion on MRI was 0.50, with an AUC of 0.9825, sensitivity of 0.9063, and specificity of 0.8663. From the present study, it was possible to measure the extrusion length and meniscal height via gradation processing, with X-ray and without MRI, and to calculate the meniscal extrusion ratio, which strongly correlates with the amount of MME on MRI.
Gastrointestinal Transit Times in Health as Determined Using Ingestible Capsule Systems: A Systematic Review
Authors: Nandhra Gursharan Kaur , Chaichanavichkij Phakanant , Birch Malcolm , Scott S. Mark
Published: August 2023

Background: Ingestible capsule (IC) systems can assess gastrointestinal (GI) transit times as a surrogate for gut motility for extended periods of time within a minimally invasive, radiation-free and ambulatory setting. Methods: A literature review of IC systems and a systematic review of studies utilizing IC systems to measure GI transit times in healthy volunteers was performed. Screening for eligible studies, data extraction and bias assessments was performed by two reviewers. A narrative synthesis of the results was performed. Results: The literature review identified 23 different IC systems. The systematic review found 6892 records, of which 22 studies were eligible. GI transit time data were available from a total of 1885 healthy volunteers. Overall, seventeen included studies reported gastric emptying time (GET) and small intestinal transit time (SITT). Colonic transit time (CTT) was reported in nine studies and whole gut transit time (WGTT) was reported in eleven studies. GI transit times in the included studies ranged between 0.4 and 15.3 h for GET, 3.3–7 h for SITT, 15.9–28.9 h for CTT and 23.0–37.4 h for WGTT. GI transit times, notably GET, were influenced by the study protocol. Conclusions: This review provides an up-to-date overview of IC systems and reference ranges for GI transit times. It also highlights the need to standardise protocols to differentiate between normal and pathological function.
Prognostic Value of the AST/ALT Ratio versus Bilirubin in Patients with Cardiogenic Shock
Authors: Schupp Tobias , Rusnak Jonas , Weidner Kathrin , Ruka Marinela , Egner-Walter Sascha , Dudda Jonas , Forner Jan , Bertsch Thomas , Mashayekhi Kambis , Ayoub Mohamed , Akin Muharrem , Kittel Maximilian , Behnes Michael , Akin Ibrahim
Published: August 2023

This study investigates the prognostic value of the aspartate-to-alanine aminotransferase ratio (i.e., AST/ALT ratio) and bilirubin in patients with cardiogenic shock (CS). Despite ongoing improvements regarding the treatment of CS patients, invasive care unit (ICU) mortality in CS patients remains unacceptably high. Limited data regarding the prognostic value of the AST/ALT ratio and bilirubin in patients suffering from CS is available. The authors hypothesize the measurement of liver enzymes during the course of CS may be an easy and feasible method to assess right-heart dysfunction and prognosis in patients with CS. Consecutive patients with CS from 2019 to 2021 were included. Blood samples were retrieved from the day of disease onset (day 1), days 2, 3, 4 and 8. The prognostic value of the AST/ALT ratio and bilirubin was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman’s correlations, Kaplan–Meier analyses, as well as multivariable Cox proportional regression analyses. A total of 157 CS patients were included, with an overall rate of all-cause mortality at 30 days of 51%. The median AST/ALT ratio on day 1 was 1.4, and the median bilirubin was 0.63 mg/dL. No association of the baseline AST/ALT ratio (HR = 1.005; 95% CI 0.649–1.558; p = 0.981) and bilirubin (HR = 1.320; 95% CI 0.834–2.090; p = 0.236) with the risk of 30-day all-cause mortality was found. In contrast, the AST/ALT ratio on day 4 was associated with the risk of 30-day all-cause mortality (HR = 2.826; 95% CI 1.227–6.510; p = 0.015), which was still evident after the multivariable adjustment (HR = 2.830; 95% CI 1.054–7.690; p = 0.039). The AST/ALT ratio during the course of ICU hospitalization from day 4—but not the baseline AST/ALT ratio and bilirubin—was associated with an increased risk of 30-day all-cause mortality in CS patients.
Analysis of Cardiac Events and the Subsequent Impact for Geriatric Patients Undergoing Hip Fracture Surgeries
Authors: Chao Ting-Cheng , Lee Hsin-Pai , Wu Jung-Chou , Hsu Chien-Jen
Published: August 2023

Perioperative complications, particularly cardiac events, compromised surgical outcomes for geriatric patients. This retrospective study intended to investigate the occurrence and subsequent impact of cardiac events for geriatric patients undergoing hip fracture surgeries. We collected 607 patients undergoing hip fracture surgeries from January 2017 to December 2022 that received transthoracic echocardiography (TTE) pre-operatively to screen for cardiac abnormalities. Except for demographic characteristics, the researchers recorded fracture type, surgical method, American Society of Anesthesiologists (ASA) class, anesthesia type, perioperative cardiac events, and in-hospital mortality. Statistical analysis was performed using SPSS 22.0 statistics software. Throughout the whole course of the study, 16 postoperative cardiac events occurred. The cardiac events included ten arrhythmias, three acute myocardial infarctions, two heart failures, and one sudden death. Notably, 12 of 16 patients with cardiac events presented with abnormal findings on TTE, except 15 of them had a history of cardiac disease. This study disclosed 93.7% of cardiac events developed in patients with a history of cardiovascular disease. Among patients that experienced cardiac events, 75% of patients had abnormal echocardiographic findings. Pre-operative transthoracic echocardiography deserves a recommendation for geriatric patients with histories of cardiac diseases undergoing hip fracture surgeries to detect the risk of developing cardiac events earlier.
Cost-Effectiveness of Exercise Therapy in Patients with Intermittent Claudication—A Comparison of Supervised Exercise, Home-Based Structured Exercise, and Walk Advice from the SUNFIT Trial
Authors: Ulfsdottir Hildigunnur , Bäck Maria , Cider Åsa , Jivegård Lennart , Sandberg Anna , Nordanstig Joakim , Svensson Mikael
Published: August 2023

Hospital-based supervised exercise (SEP) is a guideline-recommended intervention for patients with intermittent claudication (IC). However, due to the limited availability of SEP, home-based structured exercise programs (HSEP) have become increasingly popular alongside the “go home and walk” advice. We evaluated the cost-effectiveness of walk advice (WA) with Nordic pole walking vs. SEP combined with WA or HSEP combined with WA. We used data from the SUNFIT RCT (NCT02341716) to measure quality-adjusted life-years (QALYs) over a 12-month follow-up, and economic costs were obtained from a hospital cost-per-patient accounting system. Incremental cost-effectiveness ratios (ICERs) were calculated, and uncertainty was assessed using nonparametric bootstrapping. The average health-care-cost per patient was similar in the WA (EUR 1781, n = 51) and HSEP (EUR 1820, n = 48) groups but higher in the SEP group (EUR 4619, n = 50, p-value < 0.01). Mean QALYs per patient during the follow-up were similar with no statistically significant differences. The findings do not support SEP as a cost-effective treatment for IC, as it incurred significantly higher costs without providing additional health improvements over WA with or without HSEP during the one-year observation period. The analysis also suggested that HSEP may be cost-effective compared to WA, but only with a 64% probability.