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21 pages, 1109 KiB  
Article
Trusted Traceability Service: A Novel Approach to Securing Supply Chains
by A S M Touhidul Hasan, Rakib Ul Haque, Larry Wigger and Anthony Vatterott
Electronics 2025, 14(10), 1985; https://doi.org/10.3390/electronics14101985 - 13 May 2025
Viewed by 380
Abstract
Counterfeit products cause financial losses for both the manufacturer and the enduser; e.g., fake foods and medicines pose significant risks to the public’s health. Moreover, it is challenging to ensure trust in a product’s supply chain, preventing counterfeit goods from being distributed throughout [...] Read more.
Counterfeit products cause financial losses for both the manufacturer and the enduser; e.g., fake foods and medicines pose significant risks to the public’s health. Moreover, it is challenging to ensure trust in a product’s supply chain, preventing counterfeit goods from being distributed throughout the network. However, fake product detection methods are expensive and need to be more scalable, whereas a unified traceability system for packaged products is not available. Therefore, this research proposes a product traceability system, named Trusted Traceability Service (TTS), using Blockchain and Self-Sovereign Identity (SSI). The TTS can be incorporated across diverse industries because of its generic and manageable four-layer product packaging strategy. Blockchain-enabled SSI empowers distributed nodes, to verify them without a centralized client–server authorization architecture. Moreover, due to its distributed nature, the proposed TTS framework is scalable and robust, with the use of web3.0 distributed application development. The adoption of Fantom, a public blockchain infrastructure, allows the proposed system to handle thousands of successful transactions more cost-effectively than the Ethereum network. The deployment of the proposed framework in both public and private blockchain networks demonstrated its superiority in execution time and number of successful transactions. Full article
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16 pages, 3092 KiB  
Article
Potential Influence of ADAM9 Genetic Variants and Expression Levels on the EGFR Mutation Status and Disease Progression in Patients with Lung Adenocarcinoma
by Jer-Hwa Chang, Tsung-Ching Lai, Kuo-Hao Ho, Thomas Chang-Yao Tsao, Lun-Ching Chang, Shun-Fa Yang and Ming-Hsien Chien
Int. J. Mol. Sci. 2025, 26(10), 4606; https://doi.org/10.3390/ijms26104606 - 11 May 2025
Viewed by 202
Abstract
Lung adenocarcinoma (LUAD) is driven by epidermal growth factor receptor (EGFR) mutations, making it a key therapeutic target. ADAM9, a member of the A disintegrin and metalloproteinase (ADAM) family, facilitates the release of growth factors and was implicated in activating the [...] Read more.
Lung adenocarcinoma (LUAD) is driven by epidermal growth factor receptor (EGFR) mutations, making it a key therapeutic target. ADAM9, a member of the A disintegrin and metalloproteinase (ADAM) family, facilitates the release of growth factors and was implicated in activating the EGFR-mediated progression in several cancer types. In this study, we explored potential associations among ADAM9 single-nucleotide polymorphisms (SNPs), the EGFR mutation status, and the clinicopathological progression of LUAD in a Taiwanese population. In total, 535 LUAD patients with various EGFR statuses were enrolled, and allelic distributions of ADAM9 SNPs—located in promoter and intron regions, including rs78451751 (T/C), rs6474526 (T/G), rs7006414 (T/C), and rs10105311 (C/T)—were analyzed using a TaqMan allelic discrimination assay. We found that LUAD patients with at least one polymorphic G allele in ADAM9 rs6474526 had a lower risk of developing EGFR mutations compared to those with the wild-type (WT) TT genotype. Furthermore, G-allele carriers (TG + GG) of rs6474526 were associated with an increased likelihood of developing larger tumors (T3 or T4), particularly among patients with mutant EGFR. Conversely, in patients with WT EGFR, carriers of the T allele in rs10105311 had a lower risk of progressing to advanced stages (stage III or IV). Among females or non-smokers, G-allele carriers of rs6474526 demonstrated a higher risk of advanced tumor stages and distant metastases. In clinical data from the Genotype-Tissue Expression (GTEx) database, individuals with the polymorphic T allele in rs6474526 showed reduced ADAM9 expression in lung and whole blood tissues. Screening the genotype of rs6474526 in a set of LUAD cell lines revealed that cells carrying at least one minor G allele exhibited higher ADAM9 levels compared to those with the TT genotype. Additionally, analyses using TCGA and CPTAC databases revealed elevated ADAM9 expression in LUAD specimens compared to normal tissues. Elevated protein levels were correlated with advanced T stages, pathological stages, and worse prognoses. In summary, our results suggest that ADAM9 genetic variants of rs6474526 may affect ADAM9 expression and are associated with the EGFR mutation status. Both rs6474526 and rs10105311 were correlated with disease progression in LUAD patients. These variants could serve as potential biomarkers for predicting clinical outcomes. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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14 pages, 4102 KiB  
Article
Effects of Combination Treatment with Leptin and Liraglutide on Glucose Metabolism in Insulin-Dependent Diabetic Mice
by Linlin Fu, Mariko Sugiyama, Shahriar Kamal, Tsubasa Ide, Tadashi Takeda, Mitsuhiro Kuno, Hiroshi Takagi, Teruhiko Koike, Hiroshi Arima and Ryoichi Banno
Int. J. Mol. Sci. 2025, 26(10), 4595; https://doi.org/10.3390/ijms26104595 - 11 May 2025
Viewed by 171
Abstract
We investigated whether the peripheral co-administration of leptin and liraglutide (a glucagon-like peptide-1 receptor agonist) improved glucose metabolism in a mouse model of insulin-dependent diabetes mellitus (IDDM). Twelve-week-old male C57BL/6J mice were injected intraperitoneally with a high dose of streptozotocin to induce IDDM [...] Read more.
We investigated whether the peripheral co-administration of leptin and liraglutide (a glucagon-like peptide-1 receptor agonist) improved glucose metabolism in a mouse model of insulin-dependent diabetes mellitus (IDDM). Twelve-week-old male C57BL/6J mice were injected intraperitoneally with a high dose of streptozotocin to induce IDDM or vehicle-treated. Mice with IDDM were divided into four groups: leptin treatment alone (LEP), liraglutide treatment alone (LIRA), co-administration of leptin and liraglutide treatment (LEP+LIRA), untreated mice (UNT). Vehicle-treated mice were the healthy controls (HC). The blood glucose (BG) levels were measured, and a glucose tolerance test (GTT) was performed to compare the five groups. Leptin was administered peripherally at 20 μg/day using an osmotic pump, while liraglutide was administered subcutaneously at 1000 μg/kg/day. Monotherapy with leptin or liraglutide significantly improved glucose metabolism, as assessed by comparing BG levels and GTTs with those of the UNT group. Mice in the LEP+LIRA group showed even greater improvements in glucose metabolism than the monotherapy groups. Notably, glucose metabolism in the LEP+LIRA group improved comparably with the HC group. Thus, the peripheral co-administration of leptin and liraglutide effectively improved glucose metabolism in mice with IDDM without the use of insulin. Full article
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17 pages, 2209 KiB  
Article
Effect of GnRHR, BMP6 and FSHR Gene Pyramiding on Litter Traits of Goats
by Xinyue Yang, Yaokun Li, Baoli Sun, Yongqing Guo, Ming Deng, Dewu Liu and Guangbin Liu
Animals 2025, 15(10), 1358; https://doi.org/10.3390/ani15101358 - 8 May 2025
Viewed by 243
Abstract
Many studies have shown that only a few breeds of goat have the trait of high fertility, and genes play an important role in regulating litter size. This study investigated the effects of GnRHR, BMP6, and FSHR gene polymorphisms on litter [...] Read more.
Many studies have shown that only a few breeds of goat have the trait of high fertility, and genes play an important role in regulating litter size. This study investigated the effects of GnRHR, BMP6, and FSHR gene polymorphisms on litter traits in four goat breeds (Chongqing black, Chuanzhong black, Leizhou, and Nubian). Single nucleotide polymorphisms (SNPs) (g.75G > A in GnRHR, g.951T > C in BMP6, and g.-112C > T/g.3236C > A in FSHR) were genotyped using PCR-RFLP/HRM in 959 goats. Association analysis revealed significant correlations between these SNPs and litter size in the Chongqing, Chuanzhong, and Leizhou breeds, with genotypes AA (GnRHR), CC (BMP6), TT (FSHR), and AA (FSHR) linked to higher prolificacy. Polygene polymerizing effect analysis identified the optimal combinations (e.g., AATTCC, AACCAACC) with enhanced litter sizes. Tissue-specific qPCR in Chuanzhong goats showed GnRHR, BMP6, and FSHR were significantly more highly expressed in reproductive tissues (pituitary, breast, ovary, oviduct) of the prolific group than those in the non-prolific group. These SNPs serve as potential molecular markers for improving goat litter traits through polygenic selection, emphasizing the synergistic impact of multi-gene interactions on prolificacy. Full article
(This article belongs to the Special Issue Polygene and Polyprotein Research on Reproductive Traits of Livestock)
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8 pages, 1840 KiB  
Proceeding Paper
Image Descriptions for Visually Impaired Individuals to Locate Restroom Facilities
by Cheng-Si He, Nan-Kai Lo, Yu-Huan Chien and Siao-Si Lin
Eng. Proc. 2025, 92(1), 13; https://doi.org/10.3390/engproc2025092013 - 25 Apr 2025
Viewed by 172
Abstract
Since visually impaired individuals cannot observe their surroundings, they face challenges in accurately locating objects. Particularly in restrooms, where various facilities are spread across a limited space, the risk of tripping and being injured significantly increases. To prevent such accidents, individuals with visual [...] Read more.
Since visually impaired individuals cannot observe their surroundings, they face challenges in accurately locating objects. Particularly in restrooms, where various facilities are spread across a limited space, the risk of tripping and being injured significantly increases. To prevent such accidents, individuals with visual impairments need help to navigate these facilities. Therefore, we designed a head-mounted device that utilized artificial intelligence (AI) to enhance its functionality. The ESP32-CAM was implemented to capture and transmit images to a computer. The images were then converted into a model-compatible format for the bootstrapping language-image pre-training (BLIP) model to process and generate English descriptions (i.e., written captions). Then, Google Text-to-Speech (gTTS) was employed to convert these descriptions into speech, which was delivered audibly through a speaker. The SacreBLEU and MOS scores indicated that the developed device produced relatively accurate, natural, and intelligible spoken directions. The device assists visually impaired individuals in navigating and locating the restroom facilities to a satisfactory level. Full article
(This article belongs to the Proceedings of 2024 IEEE 6th Eurasia Conference on IoT, Communication and Engineering)
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12 pages, 620 KiB  
Article
rs1051931 Nonsynonymous Polymorphism of Platelet-Activating Factor Acetylhydrolase Gene PLA2G7 Is Associated with Dysesthesia and Pain Severity After Surgery
by Mayuko Hayashi, Seii Ohka, Daisuke Nishizawa, Rie Inoue, Masakazu Hayashida, Junko Hasegawa, Kyoko Nakayama, Yuko Ebata, Yuna Kang, Kaori Yoshida, Kyotaro Koshika, Ken-ichi Fukuda, Tatsuya Ichinohe and Kazutaka Ikeda
Int. J. Mol. Sci. 2025, 26(9), 3931; https://doi.org/10.3390/ijms26093931 - 22 Apr 2025
Viewed by 250
Abstract
Platelet-activating factor (PAF) is a potent inflammatory mediator that activates the PAF receptor, which induces additional PAF production. Animal studies have shown that PAF induces inflammatory and neuropathic pain, including dysesthesia, a prodromal symptom of neuropathic pain. However, in humans, the association between [...] Read more.
Platelet-activating factor (PAF) is a potent inflammatory mediator that activates the PAF receptor, which induces additional PAF production. Animal studies have shown that PAF induces inflammatory and neuropathic pain, including dysesthesia, a prodromal symptom of neuropathic pain. However, in humans, the association between PAF and pain remains unknown. Phospholipase A2 Group VII (PLA2G7) hydrolyzes PAF to eliminate PAF activity. The present study investigated the association between the PLA2G7 rs1051931 nonsynonymous polymorphism (T/C, Val379Ala), which decreases the PAF-degrading activity of PLA2G7 in plasma, and postoperative pain-related phenotypes in humans. The study included 303 patients who underwent sagittal split ramus osteotomy at Tokyo Dental College and were assessed for dysesthesia and 332 patients who underwent laparoscopic gynecologic surgery at Juntendo University Hospital and were assessed for postoperative pain using the Numeric Rating Scale (NRS). PLA2G7 rs1051931 was significantly associated with dysesthesia (p = 0.0491) and NRS scores (p = 0.0243). Carriers of the CC genotype of PLA2G7 rs1051931 were more likely to have dysesthesia and higher NRS scores than carriers of the TT + TC genotypes. Carriers of the CC genotype of PLA2G7 rs1051931 reportedly had lower PAF-degrading activity in plasma, thereby increasing the amount of PAF. The increase in PAF possibly leads to dysesthesia and postoperative pain in humans. Full article
(This article belongs to the Special Issue New Insights into the Molecular Mechanisms of Chronic Pain)
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13 pages, 2012 KiB  
Article
The Usefulness of Testosterone in Saliva Tests to Detect Testosterone Deficiency in Men with Advanced Chronic Kidney Disease: A Single-Center Study
by Ksymena Leśniak, Arkadiusz Lubas and Stanisław Niemczyk
J. Clin. Med. 2025, 14(8), 2818; https://doi.org/10.3390/jcm14082818 - 19 Apr 2025
Viewed by 826
Abstract
Background: Hypogonadism frequently occurs among men with chronic kidney disease (CKD) and is a highly unfavorable prognostic factor. Therefore, a simple and common screening for testosterone deficiency may be important. The measurement of testosterone in saliva appears to be an attractive alternative to [...] Read more.
Background: Hypogonadism frequently occurs among men with chronic kidney disease (CKD) and is a highly unfavorable prognostic factor. Therefore, a simple and common screening for testosterone deficiency may be important. The measurement of testosterone in saliva appears to be an attractive alternative to serum testosterone. This study aimed to assess the usefulness of determining free testosterone concentration in saliva to detect testosterone deficiency in men with advanced CKD, including those on dialysis. Methods: A total of 77 adult, male patients (aged 41–89 years old)—30 with CKD stage G3-G4, 30 on hemodialysis (HD), and 17 on peritoneal dialysis (PD)—were evaluated. The concentration of free testosterone was determined in saliva (SalFT), while the concentration of total testosterone (TT) was determined in blood serum. Serum-free testosterone levels were calculated (cFT). Results: SalFT did not differ from cFT in the CKD (p = 0.547) and PD groups (p = 0.409). In the HD group, SalFT was higher than cFT (p = 0.009). SalFT was positively correlated with cFT (r = 0.435 in the CKD and r = 0.479 in the HD) and TT (r = 0.451 in CKD), but only in the group of patients with SalFT levels below 140 pg/mL and 120 pg/mL, respectively. A cut-off value of SalFT ≤ 60.6 pg/mL showed 73.9% sensitivity and 77.8% specificity for testosterone deficiency recognition. Conclusions: Our study supports the value of SalFT measurement as a non-invasive approach in the diagnosis of testosterone deficiency in men with advanced CKD, as well as patients on hemodialysis. Full article
(This article belongs to the Section Nephrology & Urology)
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13 pages, 3720 KiB  
Article
Association of MTHFR and DNMT-1 Gene Polymorphisms with Acute Coronary Syndrome in Patients Admitted to the Emergency Department
by Fulya Yukcu, Murtaza Kaya, Raziye Akcilar, Fatmagul Can and Harun Yildirim
J. Clin. Med. 2025, 14(8), 2767; https://doi.org/10.3390/jcm14082767 - 17 Apr 2025
Viewed by 251
Abstract
Background/Objectives: Acute coronary syndrome (ACS) is a critical cardiovascular condition influenced by genetic and environmental factors. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and deoxyribonucleic acid methyltransferase-1 (DNMT-1) genes are linked to cardiovascular diseases, yet their specific roles in ACS pathogenesis remain unclear. This study [...] Read more.
Background/Objectives: Acute coronary syndrome (ACS) is a critical cardiovascular condition influenced by genetic and environmental factors. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and deoxyribonucleic acid methyltransferase-1 (DNMT-1) genes are linked to cardiovascular diseases, yet their specific roles in ACS pathogenesis remain unclear. This study examines the association of MTHFR C677T and DNMT-1 +32204 A/G polymorphisms with ACS and their potential contribution to genetic risk profiling. Methods: A case–control study was conducted with 212 participants, including 106 ACS patients and 106 controls. Peripheral blood samples were collected and analyzed to determine genotypic and allelic frequencies using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) technique. Statistical analyses were performed to assess associations between gene polymorphisms and ACS risk. Results: The MTHFR C677T polymorphism showed a strong association with ACS. The CC genotype significantly increased risk (OR: 7.34; 95% CI: 2.28–23.6; p < 0.001), while the C allele was also associated with higher susceptibility (OR: 2.21; 95% CI: 1.46–3.35; p < 0.001). Conversely, the T allele exhibited a protective effect, being more frequent in controls (62.9% vs. 37.1% in ACS; p = 0.000). Elevated troponin I levels in ACS patients with the TT genotype (p = 0.025) suggested a link between MTHFR variants and disease severity. However, DNMT-1 +32204 A/G polymorphisms showed no significant association with ACS risk. Conclusions: The MTHFR C677T polymorphism influences ACS susceptibility, with the CC genotype as a risk factor and the T allele offering potential protection. Full article
(This article belongs to the Section Cardiovascular Medicine)
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15 pages, 1322 KiB  
Article
Toll-like Receptor Gene Polymorphisms as Predictive Biomarkers for Response to Infliximab in Japanese Patients with Crohn’s Disease
by Jingjing Wei, Hiroki Kurumi, Hajime Isomoto, Ryohei Ogihara, Kayoko Matsushima, Haruhisa Machida, Tetsuya Ishida, Tatsuro Hirayama, Naoyuki Yamaguchi, Yukina Yoshida and Kazuhiro Tsukamoto
Diagnostics 2025, 15(8), 971; https://doi.org/10.3390/diagnostics15080971 - 10 Apr 2025
Viewed by 338
Abstract
Objectives: To explore the possible relationship between Toll-like receptor (TLR) gene encoding and a predictive outcome for the loss of response (LOR) to IFX treatment among Japanese patients with Crohn’s disease (CD). Methods: An association analysis that involved 25 single-nucleotide polymorphisms [...] Read more.
Objectives: To explore the possible relationship between Toll-like receptor (TLR) gene encoding and a predictive outcome for the loss of response (LOR) to IFX treatment among Japanese patients with Crohn’s disease (CD). Methods: An association analysis that involved 25 single-nucleotide polymorphisms (SNPs) across the TLR1, TLR2, TLR4, TLR6, TLR9, and TLR10 genes was performed on a cohort of 127 Japanese patients with CD. The therapeutic responses were evaluated at 10 weeks, 1 year, and 2 years using three different inheritance models. Results: The CD patients with a G/G genotype of rs5743565 in TLR1 were significantly less likely in the responders at 10 weeks compared with the non-responders (p = 0.023, OR = 0.206). The frequencies of the C/T or T/T genotypes of rs5743604 in the TLR1, G/A, or A/A genotypes of rs13105517 in TLR2, both in the minor allele dominant model, were significantly higher in the responders at 10 weeks as compared with those in the non-responders (p = 0.035, OR = 4.401; p = 0.017, OR = 5.473). The patients with an A/A genotype of rs13105517 in TLR2 in the minor allele recessive model were significantly less likely in the responders at one year of IFX treatment compared with those in the non-responders (p = 0.004, OR = 0.195). Conclusions: The polymorphisms of TLR1 and TLR2 can be useful as biomarkers for predicting initial and secondary LOR to IFX in Japanese CD patients. The IFX response in genetic testing may target molecules for new drugs to overcome the non-response and LOR to IFX. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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28 pages, 4704 KiB  
Article
Home Electricity Sourcing: An Automated System to Optimize Prices for Dynamic Electricity Tariffs
by Juan Felipe Garcia Sierra, Jesús Fernández Fernández, Diego Fernández-Lázaro, Ángel Manuel Guerrero-Higueras, Virginia Riego del Castillo and Lidia Sánchez-González
Big Data Cogn. Comput. 2025, 9(4), 73; https://doi.org/10.3390/bdcc9040073 - 21 Mar 2025
Viewed by 372
Abstract
Governments are focusing on citizen participation in the energy transition, e.g., with dynamic electricity tariffs, which pass part of the wholesale price volatility to end users. While often the cheapest alternative, these tariffs require micromanagement for optimization. In this research, an automated system [...] Read more.
Governments are focusing on citizen participation in the energy transition, e.g., with dynamic electricity tariffs, which pass part of the wholesale price volatility to end users. While often the cheapest alternative, these tariffs require micromanagement for optimization. In this research, an automated system capable of supplying electricity for home use at minimal cost called Smart Relays and Controller (SRC) is presented. SRC scrapes prices online, charges a battery system during the cheapest time slots and supplies electricity to the home energy system from the cheapest source, either the battery or the grid, while optimizing battery life. To validate the system, a comparison is made between SRC, a programmable scheduler and PVPC (Spain’s dynamic tariff) using twenty-eight months of hourly historical data. SRC is shown to be superior to both the scheduler and PVPC, with the scheduler performing worse than SRC but better than PVPC (T.T., p < 0.001). SRC achieves a 36.16% discount over PVPC, 13.89% when factoring in battery life. The savings are 44.24% higher with SRC than with a scheduler. Neither inflation nor incentives to reduce costs are considered. While we studied Spain’s tariff, SRC would work in any country offering dynamic electricity tariffs, with benefit margins dependent on their particularities. Full article
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19 pages, 1190 KiB  
Article
FASN, SCD, and PLAG1 Gene Polymorphism and Association with Carcass Traits and Fatty Acid Profile in Hanwoo Cattle
by Jia Yu, Sajida Naseem, Sungkwon Park, Sunjin Hur, Yoonbin Choi, Teahyung Lee, Xiangzi Li and Seongho Choi
Animals 2025, 15(6), 897; https://doi.org/10.3390/ani15060897 - 20 Mar 2025
Viewed by 410
Abstract
Genetic polymorphisms have a great impact on enhancing quantitative traits in cattle. In this study, Fatty acid synthase (FASN) g. 16024 (A>G), Stearoyl-CoA desaturase (SCD) g. 10329 (C>T), and pleomorphic adenoma gene (PLAG1) g. 25003338 (C>G) genotypic [...] Read more.
Genetic polymorphisms have a great impact on enhancing quantitative traits in cattle. In this study, Fatty acid synthase (FASN) g. 16024 (A>G), Stearoyl-CoA desaturase (SCD) g. 10329 (C>T), and pleomorphic adenoma gene (PLAG1) g. 25003338 (C>G) genotypic and allelic polymorphisms were evaluated, along with their associations with fatty acid composition, adipogenic gene expression, and carcass characteristics (carcass weight, yield grade, backfat thickness, and marbling score) in Hanwoo steers. A total of 128 Hanwoo steers were selected for this study and the Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method was used to identify polymorphism of these genes. The AG genotype and G allele in FASN g. 16024 (A>G), CT genotype and T allele in SCD g. 10329 (C>T), and GG genotype and G allele in PLAG1 g. 25003338 (C>G) showed higher frequency and positively correlated with carcass traits, yield, and quality grades. Fatty acid composition results indicate that C18:3n-6, C20:1, and C20:2n-6 were significantly higher in the AA genotype of FASN gene, C14:1 and C18:3n-6 in the CC genotype, and C16:1 in the TT genotype of SCD gene. C12:0, C14:0, C16:1, C18:0, and C20:0 were higher in the CC genotype of PLAG1 gene. Furthermore, RT-qPCR analysis of adipogenesis-related genes (AMP-activated protein kinase-α (AMPKα), Carnitine palmitoyl transferase-1β (CPT1), G-coupled protein receptor-43 (GPR43), and SCD) across different SNP genotypes suggests a systemic interaction between genetic factors and adipogenesis in beef cattle. This study emphasizes the significance of FASN g. 16024 (A>G), SCD g. 10329 (C>T), and PLAG1 g. 25003338 (C>G) SNPs for genetic selection to enhance beef quality and elucidate lipid metabolic pathways in Hanwoo cattle. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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14 pages, 1469 KiB  
Article
Loss of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Regulation and Limits Exercise Capacity
by Ji-Hyun Lee, Ik-Rak Jung, Becky Tu-Sekine, Sunghee Jin, Frederick Anokye-Danso, Rexford S. Ahima and Sangwon F. Kim
Int. J. Mol. Sci. 2025, 26(6), 2395; https://doi.org/10.3390/ijms26062395 - 7 Mar 2025
Viewed by 511
Abstract
Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways, and inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is [...] Read more.
Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways, and inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is still poorly understood. Since skeletal muscle is a major contributor to energy homeostasis, we have developed a mouse model in which skeletal muscle IPMK is specifically deleted and examined how a loss of IPMK affects whole-body metabolism. Here, we report that skeletal-muscle-specific IPMK knockout mice exhibited a ~12% increase in body weight compared to WT controls (p < 0.05). These mice also showed a significantly impaired glucose tolerance, as indicated by their ~50% higher blood glucose levels during GTT. Additionally, exercise capacity was reduced by ~45% in IPMK-MKO mice, demonstrating a decline in endurance. Moreover, these metabolic alterations were accompanied by a 2.5-fold increase in skeletal muscle triglyceride accumulation, suggesting impaired lipid metabolism. Further analysis revealed that IPMK-deficient myocytes exhibited 30% lower β-oxidation rates. Thus, our results suggest that IPMK mediates whole-body metabolism by regulating muscle metabolism and may be potentially targeted for the treatment of metabolic syndromes. Full article
(This article belongs to the Special Issue Musculoskeletal Disease: From Molecular Basis to Therapy)
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25 pages, 14389 KiB  
Article
Investigating Traffic Characteristics at Freeway Merging Areas in Heterogeneous Mixed-Flow Environments
by Shubo Wu, Yajie Zou, Danyang Liu, Xinqiang Chen, Yinsong Wang and Amin Moeinaddini
Sustainability 2025, 17(5), 2282; https://doi.org/10.3390/su17052282 - 5 Mar 2025
Cited by 1 | Viewed by 699
Abstract
The rapid development of Connected and Autonomous Vehicles (CAVs) presents challenges in managing mixed traffic flows. Previous studies have primarily focused on mixed traffic flow involving CAVs and Human-Driven Vehicles (HDVs), or on the combination of trucks and cars. However, these studies have [...] Read more.
The rapid development of Connected and Autonomous Vehicles (CAVs) presents challenges in managing mixed traffic flows. Previous studies have primarily focused on mixed traffic flow involving CAVs and Human-Driven Vehicles (HDVs), or on the combination of trucks and cars. However, these studies have not fully addressed the heterogeneous mixed traffic flow consisting of CAVs and HDVs, including trucks and cars, influenced by varying human driving styles. Therefore, this study investigates the influences of the market penetration rate (MPR) of CAVs, truck proportion, and driving style on operational characteristics in heterogeneous mixed traffic flow. A total of 1105 events were extracted from highD dataset to analyze four car-following types: car-following-car (CC), car-following-truck (CT), truck-following-car (TC), and truck-following-truck (TT). Principal Component Analysis (PCA) and clustering techniques were employed to categorize distinct driving styles, while the Intelligent Driver Model (IDM) was calibrated to represent the various car-following behaviors. Subsequently, microscopic simulations were conducted using the Simulation of Urban Mobility (SUMO) platform to evaluate the impact of CAVs on sustainable traffic operations, including road capacity, stability, safety, traffic oscillations, fuel consumption, and emissions under various traffic conditions. The results demonstrate that CAVs can significantly enhance road capacity, improve emissions, and stabilize traffic flow at high MPRs. For instance, when the MPR increases from 40% to 80%, the road capacity improves by approximately 25%, while stability enhances by approximately 33%. In contrast, higher truck proportions lead to reduced capacity, increased emissions, and decreased traffic flow stability. In addition, an increased proportion of mild drivers reduces capacity, raises emissions per kilometer, and improves stability and safety. However, a high proportion of mild human drivers (e.g., 100% mild drivers) may negatively impact traffic safety when CAVs are present. This study provides valuable insights into evaluating heterogeneous traffic flows and supports the development of future traffic management strategies for more sustainable transportation systems. Full article
(This article belongs to the Section Sustainable Transportation)
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8 pages, 781 KiB  
Article
Assessment of IL28 (rs12980275) and (rs8099917) Frequency in Recurrent Ocular Herpes Simplex Virus (HSV) Infection
by Borivoje Savic, Bozidar Savic, Tanja Kalezic, Bojana Dacic-Krnjaja, Veljko Milosevic, Sanja Petrovic Pajic, Vesna Maric, Tiana Petrovic and Svetlana Stanojlovic
Life 2025, 15(3), 389; https://doi.org/10.3390/life15030389 - 1 Mar 2025
Viewed by 632
Abstract
(1) Introduction: The main way of spreading the herpes simplex virus 1 (HSV-1) is through direct contact, as the virus enters the host via mucous membranes. Ocular infection can occur as a primary infection or as a recurrent one. The movement of HSV-1 [...] Read more.
(1) Introduction: The main way of spreading the herpes simplex virus 1 (HSV-1) is through direct contact, as the virus enters the host via mucous membranes. Ocular infection can occur as a primary infection or as a recurrent one. The movement of HSV-1 along the ophthalmic branch of the fifth cranial nerve from its latency phase in the trigeminal ganglion and its activation represent a process influenced by various symbiotic factors, such as environmental conditions and the host’s genetic characteristics. The aim of this study was to assess the frequency of IL28 (rs12980275) and (rs8099917) in recurrent ocular HSV infections. (2) Materials and methods: The study included 60 patients aged over 18, of both sexes, all of whom had a history of herpes simplex labialis (HSL). Patients were tested for HSV-1-specific IgG antibodies, and seropositive individuals were genotyped for single nucleotide polymorphisms (SNPs) rs12980275 and rs8099917. A total of 57 seropositive patients were included in the study. (3) Results: A statistically significant association was found between recurrent HSV keratitis (HSK) and heterozygous GT rs8099917 and homozygous TT rs8099917, as well as heterozygous AG rs12980275 and homozygous AA rs12980275 (p < 0.01). Interestingly, patients with homozygous GG polymorphism for both genotypes GG rs8099917 and GG rs12980275 did not develop recurrent HSV keratitis. (4) Conclusion: The most frequent SNP variations in patients with recurrent HSV disease were heterozygous AG rs12980275 (61.40%) and heterozygous GT rs8099917 (52.63%). Patients with recurrent HSV keratitis lacked the homozygous GG polymorphism in both GG rs8099917 and GG rs12980275 genotypes, suggesting that HSV-seropositive individuals expressing these genotypes may have lower predisposition to develop recurrent stromal HSV keratitis. Full article
(This article belongs to the Special Issue Cornea and Anterior Eye Diseases: 2nd Edition)
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13 pages, 2313 KiB  
Article
EPAS1 Variations and Hematological Adaptations to High-Altitude Hypoxia in Indigenous Goats in Yunnan Province, China
by Li Zhu, Lin Tang, Yunong Zhao, Shanshan Li, Xiao Gou, Weidong Deng and Xiaoyan Kong
Animals 2025, 15(5), 695; https://doi.org/10.3390/ani15050695 - 27 Feb 2025
Viewed by 558
Abstract
The EPAS1 gene plays a central role in hypoxia adaptation in high-altitude animals. Using over 400 blood samples from goats across elevations in Yunnan (500–3500 m), this study examined hematological traits, genetic polymorphisms, and protein structure. Red blood cell (RBC) and hemoglobin (HGB) [...] Read more.
The EPAS1 gene plays a central role in hypoxia adaptation in high-altitude animals. Using over 400 blood samples from goats across elevations in Yunnan (500–3500 m), this study examined hematological traits, genetic polymorphisms, and protein structure. Red blood cell (RBC) and hemoglobin (HGB) levels increased significantly with altitude (p < 0.05), reflecting improved oxygen transport. A non-synonymous SNP (g.86650 A>T, p.Gln556Leu) exhibited adaptive selection, with the T allele frequency rising at higher altitudes (p < 0.05). At 2500 m, TT genotype goats showed significantly higher RBC and HGB levels than AA genotypes (p < 0.05). Protein modeling revealed structural instability caused by the polymorphism, highlighting its role in enhancing hypoxia adaptation. These findings provide a foundation for improving high-altitude livestock genetics. Full article
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