Search Results (1,819)

In response to the global imperative to reduce greenhouse gas emissions and fossil fuel dependency, electric vehicles (EVs) have emerged as a sustainable transportation alternative, primarily utilizing lithium-ion batteries (LIBs) due to their high energy density and efficiency. However, LIBs are highly sensitive to temperature fluctuations, significantly affecting their performance, lifespan, and safety. One of the most critical threats to the safe operation of LIBs is thermal runaway (TR), an uncontrollable exothermic process that can lead to catastrophic failure under abusive conditions. Moreover, thermal runaway propagation (TRP) can rapidly spread failures across battery cells, intensifying safety threats. To address these challenges, developing advanced battery thermal management systems (BTMS) is essential to ensure optimal temperature control and suppress TR and TRP within LIB modules. This review systematically evaluates advanced cooling strategies, including indirect liquid cooling, water mist cooling, immersion cooling, phase change material (PCM) cooling, and hybrid cooling based on the latest studies published between 2020 and 2025. The review highlights their mechanisms, effectiveness, and practical considerations for preventing TR initiation and suppressing TRP in battery modules. Finally, key findings and future directions for designing next-generation BTMS are proposed, contributing valuable insights for enhancing the safety and reliability of LIB applications. Full article

SEC31A-related neurodevelopmental disorder (Halperin–Birk syndrome) was recently identified in two siblings who shared the phenotype of profound developmental delay, structural brain defects, spastic quadriplegia with multiple contractures, seizures, dysmorphism, and optic nerve atrophy. Both patients died during childhood. In this study, we identified an additional patient who suffers from global developmental delay and seizures. Genetic analysis inclusive of whole exome and genome sequencing identified a homoallelic variant in the SEC31A (p.Cys453Trp). Various in silico classifiers predicted a deleterious effect of the replacement of cystein with tryptophan at the 453rd position. Protein–protein interaction (PPI) network analysis of SEC31A revealed high-confidence interactions with SEC13, SEC23A, and SEC23B, suggesting potential regulatory roles in these processes. Structural analysis of the SEC31A–SEC13 interaction and the Cys453Trp mutant in SEC31A predicted that the stability of coat protein complex II would be compromised. Our findings support the clinical correlation of SEC31A variants with neurodevelopmental disorder. Full article

The functional properties of proteins are closely related to their structure and conformation. The effects of glycosylation and pH on the structural and conformational changes in whey protein isolate (WPI) were investigated using multispectral technology. More and higher-molecular-weight molecules of WPI–dextran conjugates (WDCs) with increased degrees of glycosylation (DGs) in SDS-PAGE occurred at the expense of band intensities of α-lactalbumin, β-lactoglobulin, and bovine serum albumin. The higher wavenumber shift in FTIR peaks of WPI after glycosylation in the Amide I, II, and III regions and the decrease in its intensity occurred. The maximum absorption wavelength (λ_max) of UV-Vis spectra of WPI before and after glycosylation in the range of 260–290 nm showed no significant difference in a pH range of 2.0–10.0. Moreover, the UV-Vis absorption intensities of WDCs at λ_max around 278 nm were highly and positively correlated with their DGs. The λ_max and intensities of total intrinsic fluorescence spectra of Tyr and Trp residues in WDCs with an increase in DGs had an obvious redshift and decrease, respectively. Although the intensities of synchronous fluorescence spectra of individual Tyr or Trp residues in WDCs with an increase in DGs also gradually decreased, the λ_max of the former and latter had a blueshift and redshift, respectively. UV-Vis absorption and fluorescence spectroscopies indicated that the changes in the λ_max and intensity of WPI were closely related to the protonation states of carbonyl groups and free amino groups and the degree of glycosylation. This work may be beneficial for understanding the structural and conformational changes in proteins by measuring the microenvironment around Tyr and/or Trp residues in proteins using UV-Vis absorption and synchronous fluorescence spectroscopies, providing a promising technique for quantitatively monitoring the degree of glycosylation (DG) in a rapid and practical way without any chemical reagents using UV-Vis absorption spectroscopy. Full article

Prostate cancer (PCa) is the second most common cancer and the second leading cause of cancer-related mortality among men. Gene expression analysis has been crucial in understanding tumor biology and providing disease progression markers. Cell surface glycoproteins and those in the extracellular matrix play significant roles in the PCa microenvironment by promoting migration, invasion, and metastasis. The molecular and histopathological heterogeneity of prostate tumors necessitates a new marker discovery to better stratify patients at risk for poor prognosis. In this study, our objectives were to investigate and characterize the localization and expression of SLIT/ROBO in PCa samples from transgenic mice and human tumor samples, aiming to identify novel prognostic markers and potential therapeutic targets. We conducted histopathological, immunohistochemical, and bioinformatics analyses on prostate tumors from two knockout mice models (Pb-Cre4/Pten^f/f and Pb-Cre4/Trp53^f/f;Rb1^f/f) and human prostate tumors. Transcriptomic analyses revealed special changes in the expression of genes related to the SLIT/ROBO neural signaling pathway. We further characterized the gene and protein expression of the SLIT/ROBO pathway in knockout animal samples, and protein expression in the PCa samples of patients with different Gleason scores. Public datasets with clinical data from patients (The Human Protein Atlas, cBioPortal, SurvExpress and CamcAPP) were used to validate the gene and protein expression of SLIT1, SLIT2, ROBO1, and ROBO4, correlating these alterations with the prognosis of subgroups of patients. Our findings highlight potential biomarkers of the SLIT/ROBO pathway with prognostic and predictive value, as well as promising therapeutic targets for PCa. Full article

Battery thermal runaway (TR) is usually accompanied by a large amount of heat release, as well as a jet of flame. This not only causes harm to the surrounding environment but even exacerbates thermal runaway propagation (TRP). At this stage, many types of materials are used to suppress TRP, and people tend to focus on improving one characteristic of the material while ignoring other properties of the material. This may leave potential pitfalls for TRP suppression, suggesting the need to study multiple properties of multiple materials. In order to better weigh the advantages and disadvantages of different types of materials when suppressing TRP, we compared three typical materials for suppressing TRP behavior in lithium-ion batteries (LIBs). These materials are phase change materials (PCM), ceramic fibers, and glass fibers. They are all available in two different thicknesses, 2 mm and 3 mm. The experiments started with a comparative analysis of the TR experimental phenomena in the presence of the different materials. Then, the temperature and mass loss of the battery module during TR were analyzed separately and comparatively. The 3 mm glass fiber showed the best inhibition effect, which extended the TR interval between cells 1 and 2 to 894 s and successfully inhibited the TR of cell 3. Compared with the blank group, the total mass loss decreased from 194.3 g to 182.2 g, which is a 6.2% reduction. Subsequently, we comprehensively analyzed the performance of the three materials in suppressing TRP by combining their suppressing mechanisms. The experimental results show that glass fiber has the best effect in suppressing TRP due to its excellent thermal insulation and mechanical properties. This study may provide new insights into how to trade-off material properties for TRP suppression in the future. Full article

A 2 × 3 factorial design was used to examine the effects of maternal probiotic supplementation (Bacillus subtilis and Bacillus amyloliquefaciens) and/or piglet dietary Trp levels on sow performance and fecal microbiota composition, as well as offspring pre-weaning performance and intestinal health parameters on the day of weaning. On day 83 of gestation, 48 sows were allocated to either: (1) control, or (2) control + probiotic (1.1 × 10⁹ colony forming units/kg of feed). Their litters were assigned to 0.22, 0.27, or 0.33% standardized ileal digestible (SID) Trp diets (0.17, 0.21 and 0.25 SID ratio of Trp to lysine (Trp:Lys), SID lysine = 1.3%). At weaning, one piglet per litter was sacrificed for intestinal health analysis. Diet had no effect on sow reproductive or offspring growth performance pre-weaning (p > 0.05). Maternal probiotic supplementation led to distinct microbial communities in the sow feces on day 114 of gestation, increasing the relative abundance of Anaerocella and Sporobacter, while decreasing Lactobacillus, Ruminococcus, and Christensenella (p < 0.05). In the offspring colonic digesta, maternal probiotic supplementation increased Dorea, Sporobacter, and Anaerobacterium, while reducing the potentially harmful phylum Proteobacteria, specifically the family Enterobacteriaceae (p < 0.05), with a tendency for a reduction in the genus Escherichia (p < 0.1). Maternal probiotic supplementation enhanced duodenal morphology and modulated the expression of genes in the ileum, including a downregulation of certain immune and barrier defense genes (p < 0.05). Piglets from probiotic sows had reduced branch chain fatty acids (BCFA) in the cecal digesta and an increase in the total VFA and acetate in the colonic digesta (p < 0.05). There were limited effects of Trp level in the offspring’s creep diet or maternal × creep interactions, though this analysis was likely confounded by the low creep feed intake (total of ~0.83 kg/litter). Full article

Congenital hypogonadotropic hypogonadism (CHH) is a rare and heterogeneous genetic disorder with variable penetrance caused by GnRH deficiency, leading to delayed puberty and infertility. In 50–60% of cases, CHH is associated with non-reproductive abnormalities, most commonly anosmia/hyposmia (Kallmann syndrome, KS). Over 60 genes have been implicated in CHH pathogenesis. We aimed to perform genetic screening in a cohort of 14 patients (10 males, 4 females; mean age 22 ± 7.72 years) with suspected or diagnosed HH/KS. Genetic analysis was conducted using next-generation sequencing (NGS) with a custom panel of 46 candidate genes. Variant interpretation followed ACMG standards and guidelines. Multiple tools were used to predict the structural effects of variants on tertiary protein structure, assessing their pathogenicity. Novel variants were functionally characterized by qRT-PCR on mRNA extracted from peripheral leukocytes. NGS identified nine rare variants and four novel variants in genes previously associated with normosmic isolated HH (nHH) and/or KS (FGFR1, PROK2, TAC3R, DCC, WDR11, IL17RD, DUSP6, KAL1, FGF8, IL17RD and DCC). The variant in TAC3R (p.Trp275Ter) was pathogenic; variants in ANOS1 (c.541+1G>A), IL17RD (c.1303_1304dup, p.Lys436ThrfsTer58), and TAC3R (p.Lys361Ter) were likely pathogenic. Nine variants were classified as variants of uncertain significance (VUS). Our study identified a possible genetic cause in 71% of the CHH/KS cohort, emphasizing the importance of genetic screening and functional characterization of genetic variants in patients with a phenotypically and genetically heterogeneous disorder like CHH. Full article

Background: Hyperuricemia (HUA) is a widespread metabolic disorder that arises from disruptions in purine metabolism, impaired kidney function, or both conditions. FPAW (Phe-Pro-Ala-Trp) is a novel peptide identified from Trachinotus ovatus with great XOD (xanthine oxidase) inhibitory activity (IC₅₀ = 3.81 mM), which can be developed as a potential active ingredient to relieve hyperuricemia. However, it remains unclear whether FPAW alleviates HUA in vivo or not. Methods: In this study, potassium-oxonate-induced hyperuricemic mice were used to evaluate the in vivo anti-hyperuricemic activity of FPAW. Some physiological parameters, such as serum uric acid (SUA), serum creatinine (SCR), blood urea nitrogen (BUN), and the activity of XOD and ADA (adenosine deaminase) in the liver were determined to evaluate the effect of reduced uric acid. The modulations in the gut microbiota and its metabolites (SCFAs) were analyzed by sequencing the V3-V4 region of the 16S rRNA gene and GC-MS in different fecal samples. Molecular docking was used to predict the interactions between the enzymes and FPAW. Results: The results showed that FPAW reduced the levels of serum uric acid, serum creatinine, and blood urea nitrogen, while also suppressing the activity of XOD in the livers of HUA mice. Moreover, the FPAW treatment alleviated gut microbiota dysfunction and increased the production of short-chain fatty acids to protect normal intestinal function and health of the host. Molecular docking simulations revealed that FPAW inhibited XOD activity by entering the hydrophobic channel and interacting with amino acid residues on the surface via hydrogen bonding and hydrophobic interactions. Conclusions: This study provides new candidates for the development of hypouricemic drugs. FPAW exhibited great potential to relieve hyperuricemia of mice induced by diet in the animal experiment. Full article

Background/Objectives: Inflammatory bowel diseases (IBDs) comprise a group of chronic idiopathic disorders, including ulcerative colitis (UC), Crohn’s disease (CD), and indeterminate colitis (IC). Complex genetic factors, in addition to environmental triggers, have been shown to play a fundamental role in the pathogenesis of IBD, contributing to disease susceptibility. The transition of adolescents with inflammatory bowel disease (IBD) to adult care represents a significant challenge for patients, their families, and healthcare providers. Approximately 25% of individuals with IBD receive a diagnosis before the age of 16, and this population is at increased risk for adverse clinical outcomes. As a result, the transition of care has garnered substantial attention in the scientific and clinical communities over the past decade. This study aims to analyze a cohort of pediatric Sardinian patients with IBD to assess clinical characteristics at diagnosis and at the time of transition and determine potential correlations between NOD2/CARD15 gene variants and HLA class II with the disease phenotype. Methods: From January 2014 to August 2024, we performed an observational, cross-sectional study that included pediatric patients with IBD enrolled in the only pediatric IBD reference center in Sardinia. Data were obtained from the patients’ medical records and from a questionnaire administered at the inclusion visit. In addition, we genotyped a portion of our cohort for the Leu1007fsinsC (SNP13), Gly908Arg (SNP12), and Arg702Trp (SNP8) variants of the NOD2/CARD15 gene, as well as for HLA-DRB1, -DQA1, and -DQB1 class II genes. The obtained results were compared with pediatric data from the national epidemiological IBD registry and existing literature. Results: Seventy-one IBD patients were enrolled (UC 43, CD 28, M 34, F 37). Median age at diagnosis was 12.2 years (IQR 2–17). After a median disease duration of 5 years (IQR: 1–16), only three UC patients experienced proximal extension of proctitis or left-sided colitis, and no CD patients experienced new localizations of disease. Fifteen patients developed extraintestinal manifestations. No significant difference was found in median diagnostic delay (DD) between UC [4 months (IQR: 1–84)] and CD patients [4.5 months (IQR: 1–48)]. At the transition visit, overall, twenty-nine patients (42%) were exposed to one biologic agent (vs. 3% at baseline; p < 0.02); 3 patients (4%) were exposed to two or more biologic agents. 7% of patients (5/71) underwent surgery. By comparing the distribution of NOD2/CARD15 SNPs between pediatric patients and an adult CD population, we found a significant association between gene allelic variants and pediatric onset (p = 0.00048). Our study also revealed a statistically significant association between Sardinian pediatric patients carrying NOD2/CARD15 mutations and early-onset CD (p < 0.009492), along with a stenosing phenotype (p < 0.024) and increased surgical risk (p < 0.026). No significant associations were observed between HLA class II alleles and IBD in our population. Conclusions: Our results provide important insights into the clinical and epidemiological features of the pediatric IBD population. In addition, our study highlights the significant role of NOD2/CARD15 gene polymorphisms in pediatric onset CD. These variants influence the age of onset and disease phenotype, characterized by greater severity and a higher risk of surgical intervention in pediatric patients. Full article

A new class of spiro[1,2,4]triazolo[1,5-c]quinazoline derivatives is presented as promising modulators of diacylglycerol kinase α (DGK-α), a target implicated in cancer, neurological disorders, and immune dysfunction. Through structure-based computational design using the CB-Dock2 platform with human DGK-α (PDB ID: 6IIE), 40 novel compounds were systematically evaluated along with established inhibitors (ritanserin, R59022, R59949, BMS502, and (5Z,2E)-CU-3) across five distinct binding pockets. Several compounds demonstrated binding profiles at the level of or surpassing the reference compounds. The physicochemical analysis revealed balanced drug-like properties with favorable molecular weights (252–412 g/mol) and appropriate three-dimensionality. The toxicological assessment indicated reassuring safety profiles with predicted LD₅₀ values of 1000–2000 mg/kg and minimal hepatotoxicity, carcinogenicity, and mutagenicity potential. Notably, compound 33 (adamantyl-substituted) emerged as exceptionally promising, exhibiting strong binding affinity, moderate solubility, and selective CYP inhibition patterns that minimize drug–drug interaction risks. Detailed molecular interaction mapping identified critical binding determinants, including strategic hydrogen bonding with TRP151, GLU166, and ARG126. The multidimensional evaluation identified compounds 13, 18, 33, and 40 as particularly promising candidates that balance potent target engagement with favorable pharmaceutical profiles, establishing this scaffold as a valuable platform for developing next-generation therapeutics targeting DGK-α -mediated signaling pathways. Full article

Breast cancer is a prevalent malignancy worldwide. Human MutT homolog 1 (MTH1) is over expressed in breast tumors, and cancer cells rely on MTH1 for survival. This protein ensures the integrity of the nucleotide pool by preventing the integration of oxidized 2′-deoxynucleoside triphosphates (dNTPs) during DNA replication. Therefore, inhibiting MTH1 pharmacologically emerged as a valid target in treating breast cancer. In the present study, we screened biologically active phytochemicals from the NPACT database to discover potential inhibitors of MTH1. Molecular docking analysis was employed to identify the binding conformation and the interaction pattern. The top five compounds were selected for detailed analysis based on their superior binding affinity and interactions with crucial residues (Asn33, Gly36, Tyr7, Phe72, Trp117, Lys23, and Phe27, Glu100) of MTH1. Additionally, the ADMET profile of selected compounds highlighted the high intestinal absorption, low toxicity, and acceptable metabolic stability, exhibiting their potential as drug candidates. Furthermore, in silico validation of selected compounds was performed through molecular dynamics (MD) simulation, which revealed that the resultant complexes are appreciably stable. Compounds revealed RMSD values ranging between 1.0 and 1.5 Å, indicating strong and stable binding conformations. PCA analysis revealed restricted conformational sampling, highlighting stabilization, particularly with ZINC14727630, ZINC14819291, ZINC14781695, and ZINC95099417. MM-GBSA confirmed the stability of the ligand–protein complexes, with ZINC14819291, ZINC14727630, and ZINC95099417 demonstrating the most stable interactions with MTH1, with total binding free energies of −32.46, −45.06, and −33.44 kcal/mol, respectively. Our results support that these natural compounds could act as potential anti-MTH1 for ameliorating the breast cancer. However, experimental validation is required to validate the efficacy of these molecules and robustness of this anticancer approach. Full article

In recent years, data from genome-wide association studies (GWAS) have shown that the genes coding for transcriptional repressor GATA binding 1 (TRPS1) and tribbles pseudokinase 1 (TRIB1) play an important role in plasma lipid profiles and act as risk factors for coronary heart disease (CHD). The aim of this work was to explore whether single nucleotide polymorphisms (SNPs) in the TRSP1 (rs231150 and rs2737229) and TRIB1 (rs2980880 and rs2954029) genes are involved in acute coronary syndrome (ACS) and plasma lipid levels. We included 1262 patients diagnosed with ACS and 1051 controls. According to inheritance models, the minor alleles of the SNPs (rs2737229 A, rs2980880 C, and rs2954029 T) were associated with an increased incidence of ACS (p < 0.05). In a sub-analysis that included only the control subjects, the same minor allele frequency was associated with increased total cholesterol, HDL-cholesterol, and LDL-cholesterol levels and low triglyceride levels. In conclusion, rs2737229, rs2980880, and rs2954029 polymorphisms are associated with a risk of developing ACS and with elevated plasma lipid levels. Our results suggest that the TRSP1 and TRIB1 are implicated in the incidence of ACS through of increased of plasma lipid profile. Full article

Stories are widely used by parents or educators to teach children the virtue of honesty. However, the existing empirical findings on the effect of story-telling on children’s honesty are limited and mixed. This study examined whether moral stories involving honesty can promote honesty in Chinese preschool children (N = 208). The Temptation Resistance Paradigm (TRP) was used to assess children’s honesty. Study 1 showed that children in the positive moral story condition were more likely to tell the truth than those in the control condition, while negative moral story-telling did not have this effect. Study 2 further examined whether combining external appeals with positive moral story-telling could further promote children’s honesty, and the results showed that the combination of the two techniques was equally as effective as moral story-telling alone. These findings have important implications for moral development and moral education. Full article

Ganoderma leucocontextum, a newly identified species from the Tibetan Plateau, has been mainly studied for its polysaccharides and triterpenoids, with no prior reports on fungal immunomodulatory proteins (FIPs). This study explores the biological activity of FIP-gle2, cloned from G. leucocontextum and expressed in Pichia pastoris. The effects and mechanisms of recombinant FIP-gle2 (rFIP-gle2) on cell activity and melanin synthesis in mouse melanoma B16-F10 cells were investigated in vitro. The results showed that the FIP-gle2 gene, with an open reading frame (ORF) of 333 bp, encodes a 111-amino acid polypeptide with a molecular weight of 12.60 kDa and an isoelectric point of 4.48. We achieved a yield of 184.18 mg/L of rFIP-gle2. In vitro functional experiments showed that rFIP-gle2 significantly inhibited the proliferation of B16-F10 melanoma cells and induced apoptosis in a dose-dependent manner, particularly at concentrations above 1 μg/mL. At 3 μg/mL, rFIP-gle2 effectively inhibited tyrosinase activity and reduced melanin content, downregulating microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), and tyrosinase-related proteins (TRP-1 and TRP-2). Furthermore, RNA-seq analysis indicated that differentially expressed genes in treated cells were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, with Western blotting confirming enhanced phosphorylation of JNK, ERK, and p38 proteins. Thus, P. pastoris is an effective host for rFIP-gle2 production, which shows potential for applications in pharmaceuticals, cosmeceuticals, and food fields. Full article

Excessive melanogenesis causes abnormal pigmentation and a higher risk of skin disorders (e.g., melanoma). Resveratrol (RSV), a natural polyphenol, exerts antioxidant and anti-aging effects. However, the effects of RSV and its derivatives on melanogenesis remain unclear. This study investigated their effects on melanogenesis and antioxidant activity in B16F10 cells. After measuring cell viability, B16F10 cells were incubated with 50 µM of RSV, dihydroresveratrol (DIRSV), and other RSV derivatives for 24 h. The relative melanin content and tyrosinase activity were quantified. The protein and mRNA levels of melanogenesis-related genes (MITF, CREB, TYR, and TRP) and the binding affinity of RSV derivatives to their target proteins were measured. The antioxidant activity was evaluated using ABTS and DPPH assays. RSV and DIRSV (50 µM) significantly reduced melanin content and tyrosinase activity, respectively. However, other derivatives had no significant effects. RSV, DIRSV, and other derivatives significantly suppressed MITF and CREB levels. Additionally, DIRSV significantly reduced p-CREB and TYR protein levels and showed a higher affinity for CREB than RSV, despite no significant changes in MITF, TYR, or TRP mRNA levels. In the antioxidant assays, RSV and DIRSV exhibited significant ABTS and DPPH radical scavenging activities. DIRSV, like RSV, inhibits melanogenesis and exhibits antioxidant effects in B16F10 cells. However, RSV derivatives demonstrate partial antioxidant activity and inhibit melanogenesis-related proteins but do not significantly affect melanogenesis. DIRSV’s practical applications as a skin-protective and -whitening agent warrant further exploration. Full article