Liver as a new target organ in Alzheimer's disease: insight from cholesterol metabolism and its role in amyloid-beta clearance.

Alzheimer's disease, the primary cause of dementia, is characterized by neuropathologies, such as amyloid plaques, synaptic and neuronal degeneration, and neurofibrillary tangles. Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs, targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment. Metabolic abnormalities are commonly observed in patients with Alzheimer's disease. The liver is the primary peripheral organ involved in amyloid-beta metabolism, playing a crucial role in the pathophysiology of Alzheimer's disease. Notably, impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease. In this review, we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism. Furthermore, we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Copeptin associates with major adverse cardiovascular events in patients on maintenance hemodialysis.

BACKGROUND: End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. OBJECTIVE: This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. METHODS: ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. RESULTS: Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. CONCLUSION: Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.

Alginate/organo-selenium composite hydrogel beads: Dye adsorption and bacterial deactivation.

Post-COVID-19, the risk and spread of germs, coupled with wastewater contamination, have become critical concerns. Wastewater contains waterborne bacteria and various contaminants like dye molecules, threatening water safety. Traditional adsorption methods address pollutant removal or pathogen inactivation separately, but a dual-action solution is increasingly essential. This study presents alginate/selenium composite hydrogel beads with the potential to simultaneously remove dyes and deactivating bacteria. Fabricated by dropping suspension droplets into a calcium ion bath, these beads were tested for dye adsorption and antibacterial efficacy. Beads with 50 wt% organo­selenium demonstrated the highest methylene blue (MB) adsorption capacity and nearly 100 % deactivation efficiency against Pseudomonas aeruginosa, while those with 20 wt% showed no significant improvement. Mechanistic studies reveal that organo­selenium induces stacking effects and reduces surface charges, enhancing MB adsorption and antibacterial performance. The alginate/organo­selenium composite hydrogel beads offer a potential effective and sustainable solution for tackling the complex issue of wastewater pollutants.

Effects of solid-state fermentation product of yeast supplementation on liver and intestinal health, and resistance of common carp (Cyprinus carpio) against spring viraemia carp virus.

This study aimed to investigate the effects of solid-state fermentation products of yeast (SFPY) on liver and intestinal health and disease resistance of common carp (Cyprinus carpio). A total of 200 common carp with an initial average weight of 2.55 ± 0.004 g were divided into 5 groups (4 replications per group and 10 fish per replication), and were fed with one of five diets, including a control diet and 4 diets supplemented with 2‰ (Y2), 3‰ (Y3), 4‰ (Y4), or 5‰ (Y5) SFPY, respectively, for 8 weeks. Results indicated that, the addition of SFPY to the diet of common carp did not affect the growth performance or survival rate of fish (P = 0.253). Interestingly, with the addition of SFPY, the triacylglycerol (TAG) content of the liver presented a linear decreasing tendency (P = 0.004), with significantly decreased in Y4 and Y5 groups (P = 0.035) compared with control. Serum lipopolysaccharide (LPS) content and diamine oxidase (DAO) activity presented a negative linear relationship with the addition of SFPY (P = 0.015, P = 0.030), while serum lipopolysaccharide binding protein (LBP) content first decreased and then increased (P < 0.001). The total antioxidant capacity (T-AOC) in the intestine of fish increased continuously with increasing SFPY supplementation (P = 0.026), reaching the highest level in Y5 group. The villus height in all experimental groups were significantly higher than that in the control group (P < 0.001). Furthermore, compared to the control, adding 3‰ SFPY to the control diet of common carp significantly increased the relative abundance of Fusobacteria (P = 0.018) and decreased that of Proteobacteria (P = 0.039) at phylum level, and increased the relative abundance of Cetobacterium (P= 0.018) and decreased that of Shewanella (P = 0.013) at genus level. Compared with the control, the relative mRNA expression level of spring viraemia of carp virus N protein (SVCV -n) in the kidney was lower than that of the control group without significance and bottomed out in Y4 group (P = 0.138). In conclusion, dietary SFPY enhanced the SVCV resistance capacity of common carp by improving liver and intestinal health and modulating the gut microbiota. Thus, SFPY is a potential feed additive to be used in aquaculture to reduce the huge economic loss of common carp due to SVCV disease. Based on liver TAG content and intestinal villus height, the optimal addition level of SFPY was 3.02‰ and 2.72‰, respectively.

Selective Vulnerability of GABAergic Inhibitory Interneurons to Bilirubin Neurotoxicity in the Neonatal Brain.

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here we report that bilirubin (BIL)-dependent cell death in auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel mediated current (Ih), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca2+-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, Ih and death, compromising audition at young adult stage in HCN1+/+, but not in HCN1-/- genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca2+ overload, neuronal death and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy.Significance Statement This study demonstrated that bilirubin preferentially targets GABAergic interneurons where it facilitates not only gating of HCN1 channels but also targeting of intracellular HCN1 to plasma membrane in calcium-dependent manner, resulting in neuronal hyperexcitability, injury and sensory dysfunction. These findings implicate HCN1 channel not only as a potential driver for auditory abnormalities in neonatal patients with bilirubin encephalopathy, but also potential intervention target for clinical management of neurological impairments associated with severe jaundice. Selective vulnerability of interneurons to neurotoxicity may be of general significance for understanding other forms of brain injury.

A Putative Effector Pst-18220, from Puccinia striiformis f. sp. tritici, Participates in Rust Pathogenicity and Plant Defense Suppression.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), stands out as one of the most devastating epidemics impacting wheat production worldwide. Resistant wheat varieties had swiftly been overcome due to the emergence of new virulent Pst strains. Effectors secreted by Pst interfere with plant immunity, and verification of their biological function is extremely important for controlling wheat stripe rust. In this study, we identified an effector, Pst-18220, from Puccinia striiformis f. sp. tritici (Pst), which was induced during the early infection stage of Pst. Silencing the expression of Pst-18220 through virus-mediated host-induced gene silencing (HIGS) resulted in a decreased number of rust pustules. In Nicotiana benthamiana, it significantly suppressed cell death induced by Pseudomonas syringae pv. tomato (Pto) DC3000. In Arabidopsis, plants with stable overexpression of Pst-18220 showed increased susceptibility to Pto DC3000, accompanied by a decrease in the expression level of pattern-triggered immunity (PTI)/effector-triggered immunity (ETI)-related genes, namely, AtPCRK1, AtPCRK2, and AtBIK1. These results emphasize the significant role of the Pst candidate effector, Pst-18220, in rust pathogenicity and the suppression of plant defense mechanisms. This broadens our understanding of effectors without any known motif.

Biomarker discovery in progressive supranuclear palsy from human cerebrospinal fluid.

BACKGROUND: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder often misdiagnosed as Parkinson's Disease (PD) due to shared symptoms. PSP is characterized by the accumulation of tau protein in specific brain regions, leading to loss of balance, gaze impairment, and dementia. Diagnosing PSP is challenging, and there is a significant demand for reliable biomarkers. Existing biomarkers, including tau protein and neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF), show inconsistencies in distinguishing PSP from other neurodegenerative disorders. Therefore, the development of new biomarkers for PSP is imperative. METHODS: We conducted an extensive proteome analysis of CSF samples from 40 PSP patients, 40 PD patients, and 40 healthy controls (HC) using tandem mass tag-based quantification. Mass spectrometry analysis of 120 CSF samples was performed across 13 batches of 11-plex TMT experiments, with data normalization to reduce batch effects. Pathway, interactome, cell-type-specific enrichment, and bootstrap receiver operating characteristic analyses were performed to identify key candidate biomarkers. RESULTS: We identified a total of 3,653 unique proteins. Our analysis revealed 190, 152, and 247 differentially expressed proteins in comparisons of PSP vs. HC, PSP vs. PD, and PSP vs. both PD and HC, respectively. Gene set enrichment and interactome analysis of the differentially expressed proteins in PSP CSF showed their involvement in cell adhesion, cholesterol metabolism, and glycan biosynthesis. Cell-type enrichment analysis indicated a predominance of neuronally-derived proteins among the differentially expressed proteins. The potential biomarker classification performance demonstrated that ATP6AP2 (reduced in PSP) had the highest AUC (0.922), followed by NEFM, EFEMP2, LAMP2, CHST12, FAT2, B4GALT1, LCAT, CBLN3, FSTL5, ATP6AP1, and GGH. CONCLUSION: Biomarker candidate proteins ATP6AP2, NEFM, and CHI3L1 were identified as key differentiators of PSP from the other groups. This study represents the first large-scale use of mass spectrometry-based proteome analysis to identify cerebrospinal fluid (CSF) biomarkers specific to progressive supranuclear palsy (PSP) that can differentiate it from Parkinson's disease (PD) and healthy controls. Our findings lay a crucial foundation for the development and validation of reliable biomarkers, which will enhance diagnostic accuracy and facilitate early detection of PSP.

Exploring and validating the necroptotic gene regulation and related lncRNA mechanisms in colon adenocarcinoma based on multi-dimensional data.

Necroptosis is intimately associated with the initiation and progression of colon adenocarcinoma (COAD). However, studies on necroptosis-related genes (NRGs) and the regulating long non-coding RNAs (NRGlncRNAs) in the context of COAD are limited. We retrieved the cancer genome atlas (TCGA) to collect datasets of NRGs and NRGlncRNAs on COAD patients. The risk model constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression was then employed to identify NRGs and NRGlncRNAs with prognostic significance. Subsequently, we validated the results using gene expression omnibus (GEO) datasets from different populations, conducted Mendelian randomization (MR) analysis to explore the potential causal relationships between prognostic NRGs and COAD, and conducted cell experiments to verify the expression of prognostic NRGlncRNAs in COAD. Furthermore, we explored potential pathways and regulatory mechanisms of these prognostic NRGlncRNAs and NRGs in COAD through enrichment analysis, immune cell correlation analysis, tumor microenvironment analysis, immune checkpoint analysis, tumor sample clustering, and so on. We identified eight NRGlncRNAs (AC245100.5, AP001619.1, LINC01614, AC010463.3, AL162595.1, ITGB1-DT, LINC01857, and LINC00513) used for constructing the prognostic model and nine prognostic NRGs (AXL, BACH2, CFLAR, CYLD, IPMK, MAP3K7, ATRX, BRAF, and OTULIN) with regulatory relationships with them, and their validation was performed using GEO and GWAS datasets, as well as cell experiments, which showed largely consistent results. These prognostic NRGlncRNAs and NRGs modulate various biological functions, including immune inflammatory response, oxidative stress, immune escape, telomere regulation, and cytokine response, influencing the development of COAD. Additionally, stratified analysis of the high-risk and low-risk groups based on the prognostic model revealed elevated expression of immune cells, increased expression of tumor microenvironment cells, and upregulation of immune checkpoint gene expression in the high-risk group. Finally, through cluster analysis, we identified tumor subtypes, and the results of cluster analysis were essentially consistent with the analysis between risk groups. The prognostic NGRlncRNAs and NRGs identified in our study serve as prognostic indicators and potential therapeutic targets for COAD, providing a theoretical basis for the clinical diagnosis and treatment of COAD and offering guidance for further research.

Regulatory mechanism of methyl jasmonate and methyl dihydrojasmonate in enhancing aroma in 'Cabernet Gernischt' via the lipoxygenase pathway.

BACKGROUND: The present study explored the effects of pre-harvest methyl jasmonates spraying on the volatiles of 'Cabernet Gernischt' grapes through the lipoxygenase pathway. Headspace solid-phase microextraction combined with gas chromatography-mass spectrometry and an enzyme-linked immunosorbent assay were utilized to analyze volatile metabolites and key enzyme activities following methyl jasmonates application. Total RNA extraction and cDNA library construction were followed by transcriptome sequencing. RESULTS: The application of 0.1 mmol L-1 methyl jasmonate and 5 mmol L-1 methyl dihydrojasmonate significantly increased the levels of C6 compounds in 'Cabernet Gernischt' berries, and also enhanced the utilization of unsaturated fatty acids as precursors in the lipoxygenase-hydroperoxides lyase pathway. The up-regulated expression of VvADH1, VvADH2, VvHPL and VvLOX2S genes led to modulations in enzyme activity, thereby enhancing the berries's aromatic profile. There was a significant correlation between linoleic and linolenic acids (i.e. the precursors of the lipoxygenase pathway) and the activities and metabolites of key enzymes. CONCLUSION: The optimal concentration of methyl jasmonates treatment favorably influences the accumulation of green leaf volatiles in 'Cabernet Gernischt' grape. © 2024 Society of Chemical Industry.

Glucose fluctuations aggravate cardiomyocyte apoptosis by enhancing the interaction between Txnip and Akt.

BACKGROUND: Glucose fluctuations may be involved in the pathophysiological process of cardiomyocyte apoptosis, but the exact mechanism remains elusive. This study focused on exploring the mechanisms related to glucose fluctuation-induced cardiomyocyte apoptosis. METHODS: Diabetic rats established via an injection of streptozotocin were randomized to five groups: the controlled diabetic (CD) group, the uncontrolled diabetic (UD) group, the glucose fluctuated diabetic (GFD) group, the GFD group rats with the injection of 0.9% sodium chloride (NaCl) (GFD + NaCl) and the GFD group rats with the injection of N-acetyl-L-cysteine (NAC) (GFD + NAC). Twelve weeks later, cardiac function and apoptosis related protein expressions were tested. Proteomic analysis was performed to further analyze the differential protein expression pattern of CD and GFD. RESULTS: The left ventricular ejection fraction levels and fractional shortening levels were decreased in the GFD group, compared with those in the CD and UD groups. Positive cells tested by DAB-TUNEL were increased in the GFD group, compared with those in the CD group. The expression of Bcl-2 was decreased, but the expressions of Bax, cleaved caspase-3 and cleaved caspase-9 were increased in response to glucose fluctuations. Compared with CD, there were 527 upregulated and 152 downregulated proteins in GFD group. Txnip was one of the differentially expressed proteins related to oxidative stress response. The Txnip expression was increased in the GFD group, while the Akt phosphorylation level was decreased. The interaction between Txnip and Akt was enhanced when blood glucose fluctuated. Moreover, the application of NAC partially reversed glucose fluctuations-induced cardiomyocyte apoptosis. CONCLUSIONS: Glucose fluctuations lead to cardiomyocyte apoptosis by up-regulating Txnip expression and enhancing Txnip-Akt interaction.

Anaerobic dynamic membrane bioreactor treating sulfamethoxazole wastewater: advantages of dynamic membrane and its fouling mechanism.

Discharge of improperly treated sulfamethoxazole (SMX) wastewater seriously threats environmental security and public health. Anaerobic dynamic membrane bioreactors (AnDMBRs) technology would be cost-effective for SMX wastewater treatment, considering its low cost and satisfactory treatment efficiency. The performance of AnDMBR, though demonstrated to be excellent in treating many types of wastewaters, was for the first time investigated for treating SMX wastewater. Particular efforts were devoted to elucidating the advantages of dynamic membrane (DM) and the governing mechanism responsible for DM fouling with the presence of SMX. The threshold SMX concentration for AnDMBR was found to be 90 mg/L and the AnDMBR exhibited excellent removal efficiency of COD (90.91 %) and SMX (88.95 %) as well as satisfactory acute toxicity reduction rate (88.84 %). It was noteworthy that the DM made indispensable contributions to the removal of COD (14.26 %) and SMX (22.20 %) as well as the acute reduction of toxicity (25.81 %). The presence of SMX significantly accelerated DM fouling mainly by increasing its specific resistance, which was attributed to the increased content of small particles, high-valence metal ions and EPS content (mainly hydrophobic proteins), resulting in a denser DM structure with lower porosity. Besides, the biofouling-related bacteria (Firmicutes) was found to be enriched in the DM with the presence of SMX.

Fluspirilene exerts an anti-glioblastoma effect through suppression of the FOXM1-KIF20A axis.

Given the infiltrative nature of human glioblastoma (GBM), cocktail drug therapy will remain a vital tool for the treatment of the disease. We investigated fluspirilene, perphenazine, and sulpiride, three classic anti-schizophrenic drugs, as possible anti-GBM agents. The CCK-8 assay demonstrated that fluspirilene possesses the most outstanding anti-GBM effect. We performed molecular mechanisms studies in vitro and an orthotopic xenograft model in mice. Fluspirilene inhibited proliferation and migration in vitro in U87MG and U251 GBM cell lines. Flow cytometry demonstrated that treatment increased apoptosis and cells accumulated in the G2/M phase. Our analysis of publicly available expression data for several cell lines treated with the drug led to the identification of several genes, including KIF20A, that are downregulated by fluspirilene and lead to growth inhibition/apoptosis. We also demonstrated that siRNA knockdown of KIF20A, a member of the kinesin family, attenuated cell proliferation in GBM cells and an orthotopic xenograft model in mice. A regulator of KIF20A, the oncogenic transcription factor FOXM1, was identified using the String database, which harbors protein interaction networks. In fluspirilene-treated cells, FOXM1 protein was decreased, indicating that KIF20A was downregulated in the presence of the drug due to decreased FOXM1 protein. These results demonstrate that fluspirilene is an effective anti-GBM agent that works by suppressing the FOXM1-KIF20A oncogenic axis.

GL5.2, a Quantitative Trait Locus for Rice Grain Shape, Encodes a RING-Type E3 Ubiquitin Ligase.

Grain weight and grain shape are important traits that determine rice grain yield and quality. Mining more quantitative trait loci (QTLs) that control grain weight and shape will help to further improve the molecular regulatory network of rice grain development and provide gene resources for high-yield and high-quality rice varieties. In the present study, a QTL for grain length (GL) and grain width (GW), qGL5.2, was firstly fine-mapped into a 21.4 kb region using two sets of near-isogenic lines (NILs) derived from the indica rice cross Teqing (TQ) and IRBB52. In the NIL populations, the GL and ratio of grain length to grain width (RLW) of the IRBB52 homozygous lines increased by 0.16-0.20% and 0.27-0.39% compared with the TQ homozygous lines, but GW decreased by 0.19-0.75%. Then, by analyzing the grain weight and grain shape of the knock-out mutant, it was determined that the annotation gene Os05g0551000 encoded a RING-type E3 ubiquitin ligase, which was the cause gene of qGL5.2. The results show that GL and RLW increased by 2.44-5.48% and 4.19-10.70%, but GW decreased by 1.69-4.70% compared with the recipient. Based on the parental sequence analysis and haplotype analysis, one InDel variation located at -1489 in the promoter region was likely to be the functional site of qGL5.2. In addition, we also found that the Hap 5 (IRBB52-type) increased significantly in grain length and grain weight compared with other haplotypes, indicating that the Hap 5 can potentially be used in rice breeding to improve grain yield and quality.

A Novel Composite Material UiO-66-Br@MBC for Mercury Removal from Flue Gas: Preparation and Mechanism.

To reduce the mercury content in flue gas from coal-fired power plants and to obtain high-performance, low-cost mercury adsorbents, a novel composite material was prepared by structural design through the in situ growth method. Functionalization treatments such as the modification of functional groups and multilayer loading of polymetallic were conducted. These materials include the MOF material UiO-66 and modified biochar doped with Fe/Ce polymetallic, both of which contain unsaturated metal centrals and oxygen-containing functional groups. On the basis of obtaining the effects of adsorption temperature and composite ratio on the Hg0 removal characteristics, coupling and synergistic mechanisms between the various types of active centers included were investigated by using a variety of characterization and analysis tools. The active adsorption sites and oxidation sites were identified during this process, and the constitutive relationship between the physicochemical properties and the performance of Hg0 removal was established. The temperature-programmed desorption technique, Grand Canonical Monte Carlo simulation, and adsorption kinetic model were employed to reveal the mechanism of Hg0 removal. The results showed that the UiO-66-Br@MBC composite adsorbent possessed an excellent Hg0 removal performance at adsorption temperatures ranging from 50 to 250 °C, and targeted construction of adsorption and oxidation sites while maintaining thermal stability. The Hg0 removal by the composites is the result of both adsorption and oxidation. The micropores and small pore mesopores in the samples provide physical adsorption sites. The modified biochar acts as a carrier to facilitate the full exposure of the central metal zirconium ions, the formation of more active sites, and the process of electron transfer. The doping modification of the Br element can enhance the overall redox ability of the sample, and the introduced Fe and Ce polymetallic ions can work in concert to promote the oxidation process of Hg0. The excellent regulation of the ratio between adsorption and oxidation sites on the surface of the composite material finally led to a significant boost in the samples' capacity to remove Hg0.

Immobilization of Lipase from Thermomyces Lanuginosus and Its Glycerolysis Ability in Diacylglycerol Preparation.

In the glycerolysis process for diacylglycerol (DAG) preparation, free lipases suffer from poor stability and the inability to be reused. To address this, a cost-effective immobilized lipase preparation was developed by cross-linking macroporous resin with poly (ethylene glycol) diglycidyl ether (PEGDGE) followed by lipase adsorption. The selected immobilization conditions were identified as pH 7.0, 35 °C, cross-linking agent concentration 2.0%, cross-linking time 4 h, lipase amount 5 mg/g of support, and adsorption time 4 h. Enzymatic properties of the immobilized lipase were analyzed, revealing enhanced pH stability, thermal stability, storage stability, and operational stability post-immobilization. The conditions for immobilized enzyme-catalyzed glycerolysis to produce DAG were selected, demonstrating the broad applicability of the immobilized lipase. The immobilized lipase catalyzed glycerolysis reactions using various oils as substrates, with DAG content in the products ranging between 35 and 45%, demonstrating broad applicability. Additionally, the changes during the repeated use of the immobilized lipase were characterized, showing that mechanical damage, lipase leakage, and alterations in the secondary structure of the lipase protein contributed to the decline in catalytic activity over time. These findings provide valuable insights for the industrial application of lipase.

Effect of thermal pretreatments on the quality attributes and irradiation markers of sesame oil extracted from sesame seeds without and with gamma irradiation.

This study comparatively studied the effects of three thermal pretreatment methods, i.e., wet-heat (WT), roasting (RT) and microwave (MT), on the quality attributes and irradiation markers of sesame oil obtained from sesame seeds without and with gamma irradiation. Results showed that gamma irradiation had negligible effect on the quality of sesame seeds and their extracted oils. The effects of thermal pretreatments on irradiated and non-irradiated sesame seeds and their oils were similar, little synergistic effects were observed. The RT-treated oils had more carotenoids, chlorophyll, total phenols, tocopherols, and heterocyclic volatiles content, as well as longer oxidation induction time, but darker color compared with their WT- and MT-treated counterparts. All oil samples had identical FTIR spectra. Eight radiolytic hydrocarbons were identified in the irradiated sesame oils. Thermal pretreatments reduced the content of radiolytic hydrocarbons, but did not significantly change their composition. Our study helps to identify products from irradiated sesame seeds.

IGF2BP1-mediated the stability and protein translation of FGFR1 mRNA regulates myogenesis through the ERK signaling pathway.

N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification of RNAs and plays a key regulatory role in various biological processes. As a member of the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) family, IGF2BP1 has recently demonstrated its ability to specifically bind m6A-modified sites within mRNAs and effectively regulate their mRNA stability. However, the precise roles of IGF2BP1 in mammalian skeletal muscle development, along with its downstream mRNA targets during myogenesis, have yet to be fully elucidated. Here, we observed that IGF2BP1 expression significantly decreased during myogenic differentiation. Knockdown of IGF2BP1 significantly inhibited myoblast proliferation while promoted myogenic differentiation. In contrast, IGF2BP1 overexpression robustly stimulated myoblast proliferation but suppressed their differentiation. Combined analysis of high-throughput sequencing and RNA stability assays revealed that IGF2BP1 can enhance fibroblast growth factor receptor 1 (FGFR1) mRNA stability and promote its translation in an m6A-dependent manner, thereby regulating its expression level and the Extracellular Signal-Regulated Kinase (ERK) pathway. Additionally, knockdown of FGFR1 rescued the phenotypic changes (namely increased cell proliferation and suppressed differentiation) induced by IGF2BP1 overexpression via attenuating ERK signaling. Taken together, our findings suggest that IGF2BP1 maintains the stability and translation of FGFR1 mRNA in an m6A-dependent manner, thereby inhibiting skeletal myogenesis through activation of the ERK signaling pathway. This study further enriches the understanding of the molecular mechanisms by which RNA methylation regulates myogenesis, providing valuable insights into the role of IGF2BP1-mediated post-transcriptional regulation in muscle development.

Synergistic Enhancement of Biaxial Stretching and Multilayer Composites in All-Solid-State Polymer Electrolytes.

As an important component of lithium-ion batteries, all-solid-state electrolytes should possess high ionic conductivity, excellent flexibility, and relatively high mechanical strength. All-solid-state polymer electrolytes (ASSPEs) based on polymers seem to be able to meet these requirements. However, pure ASSPEs have relatively low ionic conductivity, and the addition of inorganic fillers such as lithium salts will reduce their flexibility and mechanical strength. To address the above issues, in this paper, the solvent-free method was used to prepare a poly(vinylidenefluoride-co-hexafluoropropylene)/lithium bis(trifluoromethanesulfonyl) imide/poly(ethylene oxide) all-solid-state polymer electrolyte, which was then subjected to 4 × 4 magnification synchronous bidirectional stretching. Subsequently, it was multilayered with PEO-based composite polymer electrolytes to obtain multilayered composite polymer electrolytes (MCPEs). Bidirectional stretching provides superior in-plane and out-of-plane mechanical properties to MCPEs by inducing molecular chain orientation, which suppresses the growth of lithium dendrites. Concurrently, it facilitates the formation of the ß-crystal form of PVDF-HFP, thereby weakening the ion solvation effect and reducing the lithium-ion migration energy barrier. Multilayered compounding improves the interfacial contact between MCPEs and electrodes, thereby reducing the interfacial impedance. Experiments have demonstrated that the MCPEs prepared in this paper exhibit high ionic conductivity at room temperature (1.83 × 10-4 S cm-1), low interfacial resistance (547 Ω cm-2), excellent mechanical properties (26 MPa), and excellent cycling rate performance (a capacity retention rate of 90% after 110 cycles at 0.1 C), which can meet the performance requirements of lithium-ion batteries for ASSPEs.

Divergent Synthesis and Antigenicity Evaluation of Core Oligosaccharides of the Lipopolysaccharides from Acinetobacter baumannii SMAL and ATCC 19606.

Acinetobacter baumannii poses a serious threat to human health. Pathogenic bacterial lipopolysaccharides (LPSs) are potent immunogens for the development of antibacterial vaccines. To investigate the antigenic properties of A. baumannii LPS, five well-defined core oligosaccharide fragments from the LPS of A. baumannii SMAL and ATCC 19606 were synthesized. A divergent synthesis strategy based on orthogonally protected α-(2 → 5)-linked Kdo dimer 6 was developed. Selective exposure of different positions in this key precursor and then elongation of sugar chains via stereocontrolled formation of both 1,2-trans and 1,2-cis-2-aminoglycosidic linkages permitted the efficient synthesis of the targets. The synthetic route also highlights a 4-O and then 7-O glycosylation sequence for assembly of the novel 4,7-branched Kdo framework. Antigenicity assay using the glycan microarray technique disclosed that tetrasaccharide 3 featuring both 4,7-branch and α-(2 → 5)-Kdo-Kdo structural elements was a potential antigenic determinant.

Characterization of Two Novel HIV-1 CRF01_AE/CRF07_BC Recombinant Forms Among Men Who Have Sex with Men and Mother-to-Child Transmission Cases in Baoding City, China.

CRF01_AE and CRF07_BC are predominant circulating HIV-1 subtypes in China. In this study, we report two novel HIV-1 CRF01_AE/CRF07_BC recombinant forms isolated from one man who has sex with men (MSM) (BDD027) and one mother-to-child transmission (MTCT) case (BDL123) in Baoding City, Hebei Province, China. The recombination breakpoint analysis showed that the recombination pattern of the near-full-length genome of BDD027 consisted of two CRF07_BC fragments inserted into a CRF01_AE backbone, while the recombination pattern of the near-full-length genome of BDL123 consisted of one CRF01_AE fragment inserted into a CRF07_BC backbone. This study demonstrates the importance of strengthening the monitoring of HIV-1 molecular epidemiological characteristics and emphasizes the urgent need to reduce the HIV-1 epidemic among MSM and MTCT populations in China.