Search Results (56)

6-PPD quinone (6-PPDQ) is a derivative from 6-PPD, an antioxidant added in tires. Leucine is an important amino acid that needs to be obtained from the diet. In Caenorhabditis elegans, we examined the effect of 6-PPDQ exposure at environmentally relevant concentrations (ERCs) on the content of leucine and underlying mechanisms. In nematodes, 0.1–10 μg/L of 6-PPDQ decreased leucine content. The expression of the aat-1-encoding amino acid transmembrane transporter was decreased by 0.1–10 μg/L of 6-PPDQ, and leucine content was reduced by aat-1 RNAi. Meanwhile, the expression of bcat-1-encoding branched-chain amino acid transferase was increased by 0.1–10 μg/L of 6-PPDQ, and leucine content was increased by bcat-1 RNAi. Additionally, the expressions of dbt-1 and ivd-1 encoding two enzyme genes governing NADH and FADH₂ generations were decreased by 0.1–10 μg/L of 6-PPDQ, and their expressions in 6-PPDQ exposed nematodes were increased by bcat-1 RNAi. After 6-PPDQ exposure, NADH content was reduced by dbt-1 RNAi, and FADH₂ content was reduced by ivd-1 RNAi. Moreover, 6-PPDQ-induced mitochondrial dysfunction and other aspects of toxicity (such as intestinal ROS generation and lipofuscin accumulation, inhibited locomotion, and reduced brood size) were suppressed by bcat-1 RNAi and strengthened by dbt-1 and ivd-1 RNAi. The 6-PPDQ-induced toxicity and the decrease in dbt-1 and ivd-1 expressions could be inhibited by following leucine (5 mM) treatment. Our results demonstrate the important association of leucine adsorption and catabolism with 6-PPDQ toxicity induction. Full article

Agaricus bisporus is popular worldwide because of its high nutritional value and low cost. Low-temperature storage is a common storage method used for the production and sales of A. bisporus cultivation spawn, but few studies have focused on the physiological and biochemical mechanisms associated with low-temperature storage of A. bisporus cultivation spawn. In this study, we examined A. bisporus spawn samples stored for different refrigeration periods (0, 20, 40, 60, 80, and 100 days), measured changes in the activities of four key extracellular enzymes and performed transcriptomic and metabolomic analyses. The results of the enzymatic assays revealed that the activities of carboxymethyl cellulase (CMCase), amylase, and acid protease initially decreased before increasing, whereas laccase activity showed the opposite trend. This pattern may represent an energy supply mechanism adopted by A. bisporus to cope with low temperatures, where extracellular enzymes indirectly influence survival by mediating substrate decomposition. Further correlation analysis on the basis of CMCase activity changes revealed 148 carboxymethyl cellulase-correlated metabolites (CCMs) and 514 carboxymethyl cellulase-correlated genes (CCGs) (p ≤ 0.05), and significance was determined at FDR < 0.05 with a fold change > 1.5. Among these, 56.08% of the CCMs and 63.04% of the CCGs presented positive correlations with CMCase activity, whereas 43.92% and 36.96% presented negative correlations, respectively. Integrated multiomics analysis revealed significant variations in metabolic flux and gene expression across different storage durations. Two CCMs (ketoleucine and 3-methyl-2-oxovaleric acid) gradually decreased in expression, whereas two CCGs (AbbBCAT and AbbAACS) increased in expression. This study provides novel insights into the molecular adaptation of A. bisporus spawn to refrigeration, highlighting the importance of branched-chain amino acid metabolism in the cold stress response and storage stability. Full article

Sugarcane (Saccharum officinarum L.) faces significant challenges in China, including labor-intensive cultivation, low yields, and environmental stresses. Enhancing root development and stress tolerance through phytohormones and molecular breeding is a promising approach to boosting productivity. Indole-3-butyric acid is a phytohormone known for promoting root development and stress resistance. However, its effects on sugarcane root development under low temperature remain poorly understood. This study demonstrated that IBA markedly promoted root initiation, elongation, and biomass under low temperature, and significantly increased the levels of phytohormones, including GA₃, ABA, JA, IAA, and ZT, suggesting the activation of multiple signaling pathways. Transcriptome analysis revealed numerous differentially expressed genes related to metabolic pathways such as glycolysis, the tricarboxylic acid cycle, and glutathione metabolism. Weighted gene co-expression network analysis identified core gene modules correlated with phytohormone activities, highlighting their role in the IBA-mediated stress response. Eleven core genes, including GSTU6, FAR1, and BCAT3, and nine hub genes, such as Ub-CEP52-1 and ACS1, were identified as critical components for IBA-induced root development and stress mitigation. These findings provide insights into the molecular mechanisms underlying IBA-induced root development and stress tolerance in sugarcane, offering candidate genes for breeding high-yield, stress-tolerant varieties and demonstrating IBA’s potential as a strategy to enhance productivity under challenging conditions. Full article

Carbohydrate metabolism disorders (CMDs), including prediabetes and type 2 diabetes mellitus (T2DM), are increasingly prevalent in the aging population. Oxidative stress (OxS) plays a pivotal role in CMD pathogenesis, with extracellular superoxide dismutase (SOD3) and catalase (CAT) serving as critical antioxidant defenses. Additionally, microRNAs (miR-21 and miR-30b) regulate the oxidative and inflammatory pathways, yet their roles in elderly CMD patients remain unclear. This study evaluated miR-21 and miR-30b expression alongside SOD3 and CAT plasma levels in individuals aged ≥ 65 years (n = 126) categorized into control (n = 38), prediabetes (n = 37), and T2DM (n = 51) groups. Quantitative PCR assessed miRNA expression, while ELISA measured the enzyme levels. SOD3 levels were significantly reduced in CMDs, particularly in T2DM, whereas miR-21 was upregulated. A negative correlation between SOD3 and miR-21 was strongest in T2DM, suggesting a regulatory interplay. Neither CAT levels nor miR-30b expression differed among groups. Logistic regression indicated SOD3 as a protective biomarker, with each 1 ng/mL increase reducing the CMD risk by ~5–6%. The ROC analysis supported SOD3’s diagnostic potential, while miR-21 showed a modest association. These findings highlight SOD3 downregulation and miR-21 upregulation as potential contributors to CMD progression in elderly patients, warranting further research into their mechanistic roles and therapeutic potential. Full article

Branched-chain amino acid aminotransferases (BCATs), existing as the two isoforms BCAT1 and BCAT2, are responsible for the catabolism of branched-chain amino acids (BCAAs) and are highly upregulated and implicated in a diverse range of cancers. BCAT1 inhibitors represent a potential class of therapeutic agents for cancers; however, none have yet progressed to clinical development. Our earlier research identified WQQ-345 as a novel BCAT1 inhibitor featuring a unique bridged bicyclic skeleton and demonstrating both in vitro and in vivo antitumor activity against tyrosine kinase inhibitor (TKI)-resistant lung cancer with high BCAT1 expression. In the present study, we proceeded to modify the structure of WQQ-345 by two-round structure–activity relationship (SAR) exploration, leading to the discovery of a bicyclo[3.2.1]octene-bearing GABA derivative 7. Compound 7 exhibited a 6-fold enhancement in BCAT1 enzymatic inhibitory activity compared to the parent compound WQQ-345 and could effectively suppress the growth of 67R cells that highly expressed BCAT1 and was resistant to third-generation TKIs. GABA derivatives are an important chemical class of BCAT1 inhibitors, and therefore, the findings in the present study represent great progress both in the discovery of potent BCAT1 inhibitors with new chemical structures and in the treatment of cancer resistance. Full article

This study investigates the impact of four parameters—gate angles, fin height controlled through gate overlaps and the distance from fin to source/drain, and substrate bottom doping concentration—on the row hammer effect (RHE) in DRAM cells. The influence of adjacent and passing gates on the DRAM cell body potential was identified as a key factor in D0 and D1 failures. The tolerance for D1 and D0 failures was analyzed, defined as the threshold number of pulses required to induce a 0.6 V change in the storage node voltage (from 1.2 V to 0.6 V for a D1 failure or from 0 V to 0.6 V for a D0 failure). D1 (D0) failure tolerances with the slope from the top of the top gate (θ_angle) of 3°, the height of the TiN gate covering the fin (H_{fin_overlap}) of 12.5 nm, and the height of the fin (H_fin) of 12.5 nm are 1.26 × 10⁶ (4.8 × 10⁶), 1.14 × 10⁶ (4 × 10⁷), and 7.5 × 10⁵ (4.8 × 10⁵), respectively. Higher θ_angles and smaller fin heights generally result in higher RHE tolerances. Although decreasing the fin height reduced the RHE, it also decreased the on-current and resulted in an increase in the threshold voltage (V_T) and the subthreshold swing (SS). In addition, by increasing the substrate bottom doping concentration (P_{dop_bot}), we improve RHE tolerance twice its original level without reducing the on-current. Therefore, designing a buried channel array transistor (BCAT) structure requires careful consideration of these trade-offs, and a thorough understanding of the underlying mechanism is crucial to devising strategies that reduce RHE tolerance. The findings of this study are expected to contribute significantly to the development of next-generation DRAM architectures, enhancing stability and performance. By addressing the reliability challenges posed by advanced scaling, this study paves the way for the ongoing advancement of DRAM technology for high-density and high-performance applications. Full article

Leucine, isoleucine, and valine are collectively known as branched chain amino acids (BCAAs) and are often discussed in the same physiological and pathological situations. The two consecutive initial reactions of BCAA catabolism are catalyzed by the common enzymes referred to as branched chain aminotransferase (BCAT) and branched chain α-keto acid dehydrogenase (BCKDH). BCAT transfers the amino group of BCAAs to 2-ketoglutarate, which results in corresponding branched chain 2-keto acids (BCKAs) and glutamate. BCKDH performs an oxidative decarboxylation of BCKAs, which produces their coenzyme A-conjugates and NADH. BCAT2 in skeletal muscle dominantly catalyzes the transamination of BCAAs. Low BCAT activity in the liver reduces the metabolization of BCAAs, but the abundant presence of BCKDH promotes the metabolism of muscle-derived BCKAs, which leads to the production of glucose and ketone bodies. While mutations in the genes responsible for BCAA catabolism are involved in rare inherited disorders, an aberrant regulation of their enzymatic activities is associated with major metabolic disorders such as diabetes, cardiovascular disease, and cancer. Therefore, an understanding of the regulatory process of metabolic enzymes, as well as the functions of the BCAAs and their metabolites, make a significant contribution to our health. Full article

Increased expression of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) often correlates with tumor aggressiveness and drug resistance in cancer. We have recently reported that BCAT1 was overexpressed in a subgroup of T-cell acute lymphoblastic (T-ALL) samples, especially those with NOTCH1 activating mutations. Interestingly, BCAT1-depleted cells showed pronounced sensitivity to DNA-damaging agents such as etoposide; however, how BCAT1 regulates this sensitivity remains uncertain. Here, we provide further clues on its chemo-sensitizing effect. Indeed, BCAT1 protein regulates the non-homologous end joining (c-NHEJ) DNA repair pathway by physically associating with the KU70/KU80 heterodimer. BCAT1 inhibition during active repair of DNA double-strand breaks (DSBs) led to increased KU70/KU80 acetylation and impaired c-NHEJ repair, a dramatic increase in DSBs, and ultimately cell death. Our results suggest that, in T-ALL, BCAT1 possesses non-metabolic functions that confer a drug resistance mechanism and that targeting BCAT1 activity presents a novel strategy to improve chemotherapy response in T-ALL patients. Full article

Dynamic random-access memory (DRAM) is crucial for high-performance computing due to its speed and storage capacity. As the demand for high-capacity memory increases, DRAM has adopted a scaled-down approach for the next generation. However, the reduced distance between cells leads to electrical interference, known as the 1-row Hammer effect, which degrades DRAM performance and poses security risks. Therefore, the 1-row Hammer effect is a critical issue in current DRAM technology. In this study, we investigate the principles and impact of the 1-row Hammer phenomenon on DRAM. The 1-row Hammer effect can cause two types of failures: D0 and D1. We focus on D0 failures, which occur when stored data transition from 0 to 1 due to repeated accesses. This phenomenon involves the capture and diffusion of electrons, influenced by interfacial traps and device structures. To investigate the D0 failure, we simulated the 1-row Hammer effect using a mixed-mode approach to examine its effects on interfacial traps and device structure changes. This study aims to improve our understanding of row Hammer and suggests a mitigation strategy using buried oxide. The proposed structure mitigates the D0 failure by approximately 25%, effectively improving the security and reliability of DRAM. Full article

To adopt the blockchain-based automobile traceability system (BCATS) and increase the transparency of the Chinese auto market, this study constructs a tripartite evolutionary game model of manufacturers, regulators, and consumers, discusses the evolutionary stabilization strategy (ESS) under different cases, and analyzes the influencing factors on the tripartite ESS through numerical simulation. The study finds that there exists an ESS of blockchain adoption and tripartite cooperation, and it is influenced by different factors including blockchain construction cost, traceability service price, and government subsidy. Lowering the blockchain construction cost, and increasing the traceability service price and government subsidy can all have a positive impact on accomplishing the ideal ESS, but the latter two can also have a negative impact when they are beyond the scope of effectiveness. The study results provide practical recommendations for adopting blockchain in the auto traceability, which can help to promote blockchain in the Chinese auto market. Full article

As semiconductor devices become smaller, their performance and integration density improve, but new negative effects emerge due to the reduced distance between structures. In DRAM, these effects can lead to data loss or require additional refresh cycles, causing performance degradation. Specifically, in the 6F² DRAM structure, activating a word line (WL) lowers the energy barrier of adjacent WLs, leading to the Pass Gate Effect (PGE). This study investigates the use of buried oxide beneath the WL to mitigate the PGE through simulation. Using SILVACO TCAD, we analyzed the impact of varying the size and position of the buried oxide on the PGE. The results showed that increasing the oxide size or reducing the distance to the WL effectively reduced the PGE. However, the presence of interface traps, which increase with the addition of buried oxide, was found to exacerbate the PGE, indicating that minimizing interface traps is crucial when incorporating buried oxide. Full article

Branched-chain amino acids (BCAAs) are essential for muscle protein synthesis and are widely acknowledged for mitigating sarcopenia. Oligonol^® (Olg), a low-molecular-weight polyphenol from Litchi chinensis, has also been found to attenuate sarcopenia by improving mitochondrial quality and positive protein turnover. This study aims to investigate the effect of Olg on BCAA-stimulated protein synthesis in sarcopenia. In sarcopenic C57BL/6 mice and senescence-accelerated mouse-prone 8 (SAMP8) mice, BCAAs were significantly decreased in skeletal muscle but increased in blood serum. Furthermore, the expressions of membrane L-type amino acid transporter 1 (LAT1) and branched-chain amino acid transaminase 2 (BCAT2) in skeletal muscle were lower in aged mice than in young mice. The administration of Olg for 8 weeks significantly increased the expressions of membrane LAT1 and BCAT2 in the skeletal muscle when compared with non-treated SAMP8 mice. We further found that BCAA deprivation via LAT1-siRNA in C2C12 myotubes inhibited the signaling of protein synthesis and facilitated ubiquitination degradation of BCAT2. In C2C12 cells mimicking sarcopenia, Olg combined with BCAA supplementation enhanced mTOR/p70S6K activity more than BCAA alone. However, blocked LAT1 by JPH203 reversed the synergistic effect of the combination of Olg and BCAAs. Taken together, changes in LAT1 and BCAT2 during aging profoundly alter BCAA availability and nutrient signaling in aged mice. Olg increases BCAA-stimulated protein synthesis via modulating BCAA transportation and BCAA catabolism. Combining Olg and BCAAs may be a useful nutritional strategy for alleviating sarcopenia. Full article

Burdock fructooligosaccharide (BFO) is fructose with a low polymerization degree, which could improve the immunity to pathogens, quality, and stress resistance of vegetables. Still, there are no studies on applying BFO in Chinese cabbage. In this study, the effects of exogenous BFO sprayed with different concentrations (0, 5, 10, 20, 30 g·L⁻¹) on the growth and soluble sugar content of Chinese cabbage seedlings were determined. The result showed that 10 g·L⁻¹ was the appropriate spraying concentration. Based on metabolome analysis, a total of 220 differentially accumulated metabolites (DAMs) were found, among which flavonoid metabolites, glucosinolate metabolites, and soluble sugar-related metabolites were the key metabolites involved in improving the quality of Chinese cabbage caused by BFO. Further combination analysis with transcriptome, trans-cinnamate 4-monooxygenase (CYP73A5), and chalcone synthase 1 (CHS1) were more closely associated with the DAMs of flavonoid biosynthesis. Sulfotransferases 18 (SOT18), Branched-chain amino acid amino transferases 6 (BCAT6), and cytochrome P450 monooxygenase (CYP83A1) were the key genes in glucosinolate biosynthesis. Hexokinase (HxK1), beta-glucosidase 8 (BGL08), invertase 3 (INV3), beta-glucosidase 3B (BGL3B), and sucrose phosphate synthase 1 (SPS1) were significantly upregulated, potentially playing crucial roles in the soluble sugar metabolism. In conclusion, these results provided an understanding of the effects of BFO on the expression of genes and the accumulation of metabolites related to quality formation in Chinese cabbage. Full article

Small ruminant lentivirus (SRLV) infections are spread in the flocks of sheep and goats all over the world, causing economic loss. Although only a fraction of infected animals develop disease symptoms, all of them may shed the virus, causing uncontrolled spread of the infection. Antibodies against the virus can be detected in the blood of infected animals and are the main marker of infection. Additionally, in most infected animals, proviral DNA can also be detected, but at different levels. Due to the lack of treatment or vaccines, the most effective strategy to prevent SRLV infections are control programmes introduced by several countries based on the elimination of seropositive individuals from the flock. An alternative approach, which has currently become the rationale, is an identification of host factors which may predispose certain individuals or breeds to resistance or susceptibility to small ruminant lentivirus infection. In our work, attention was paid to goats of the Carpathian breed infected with SRLV. Available RNA-seq results from the blood of 12 goats with a determined level of SRLV proviral load were used to analyse single nucleotide polymorphisms (SNPs) by the variant calling method. Six SNPs within five genes (POU2AF1, BCAT2, TMEM154, PARP14, UBASH3A) were selected for genotyping to determine their association with the level of small ruminant lentivirus proviral DNA in a group of 60 goats. Interestingly, in seronegative individuals, only the TT genotype of the PARP14 gene was observed, while the TMEM154 CC genotype was found only in seropositive goats. Both genes may be considered potential markers for resistance/susceptibility to SRLV infection. In contrast, polymorphisms identified in POU2AF1 and UBASH3A genes seemed to be deleterious for respective protein functions; therefore, these genes are less likely to be recognised as resistance/susceptibility markers of SRLV infection. Full article

Water scarcity is a major environmental constraint on plant growth in arid regions. Soluble sugars and amino acids are essential osmolytes for plants to cope with osmotic stresses. Sweet sorghum is an important bioenergy crop and forage with strong adaptabilities to adverse environments; however, the accumulation pattern and biosynthesis basis of soluble sugars and amino acids in this species under osmotic stresses remain elusive. Here, we investigated the physiological responses of a sweet sorghum cultivar to PEG-induced osmotic stresses, analyzed differentially accumulated soluble sugars and amino acids after 20% PEG treatment using metabolome profiling, and identified key genes involved in the biosynthesis pathways of soluble sugars and amino acids using transcriptome sequencing. The results showed that the growth and photosynthesis of sweet sorghum seedlings were significantly inhibited by more than 20% PEG. After PEG treatments, the leaf osmotic adjustment ability was strengthened, while the contents of major inorganic osmolytes, including K⁺ and NO₃⁻, remained stable. After 20% PEG treatment, a total of 119 and 188 differentially accumulated metabolites were identified in the stems and leaves, respectively, and the accumulations of soluble sugars such as raffinose, trehalose, glucose, sucrose, and melibiose, as well as amino acids such as proline, leucine, valine, serine, and arginine were significantly increased, suggesting that these metabolites should play key roles in osmotic adjustment of sweet sorghum. The transcriptome sequencing identified 1711 and 4978 DEGs in the stems, as well as 2061 and 6596 DEGs in the leaves after 20% PEG treatment for 6 and 48 h, respectively, among which the expressions of genes involved in biosynthesis pathways of sucrose (such as SUS1, SUS2, etc.), trehalose (including TPS6), raffinose (such as RAFS2 and GOLS2, etc.), proline (such as P5CS2 and P5CR), leucine and valine (including BCAT2), and arginine (such as ASS and ASL) were significantly upregulated. These genes should be responsible for the large accumulation of soluble sugars and amino acids under osmotic stresses. This study deepens our understanding of the important roles of individual soluble sugars and amino acids in the adaptation of sweet sorghum to water scarcity. Full article