Search Results (644)

Objectives: The objectives of this study are to investigate the therapeutic targets and mechanisms of proanthocyanidins in alleviating fluoride-induced liver injury through network pharmacology and animal experimental validation and to explore the medicinal value of grape seed proanthocyanidins. Methods: Potential targets of proanthocyanidins were predicted using databases such as PubChem, SwissTargetPrediction, and GeneCards, and disease-related targets of fluoride-induced liver injury were retrieved to identify common targets between proanthocyanidins and fluoride-induced liver injury. The STRING database was utilized to construct a protein–protein interaction network, and key targets were analyzed for network topology using Cytoscape software. GO and KEGG enrichment analyses were performed on core target genes to explore the potential molecular mechanisms by which proanthocyanidins alleviate fluoride-induced liver injury. The Genes-miRNA interaction network was generated using Networkanalyst, and the molecular docking results between active components and key targets were validated using the CB-Dock2 visualization tool. In the academic context, a rat model of chronic fluoride poisoning was successfully established by means of intragastric administration of sodium fluoride. The protein expression levels of p-mTOR, p-p70s6, p62, LC3-II, and PARP1 in rat liver tissues were detected via Western blot analysis. Results: Network pharmacological analysis successfully identified 96 key genes, through which proanthocyanidins mitigate fluoride-induced liver injury. KEGG enrichment analysis predicted that proanthocyanidins mainly exert their therapeutic effects through the mTOR signaling pathway. The molecular docking results further demonstrated strong binding affinities between proanthocyanidins and key targets, including mTOR and PARP1. The in vivo experimental results indicate that, compared with the control group, the protein expression levels of p-mTOR, p-p70s6k, and p62 in the liver tissues of rats exposed to sodium fluoride significantly increase. Conversely, the protein expression levels of LC3-II and PARP1 significantly decrease (p < 0.05). The outcome of liver intervention with proanthocyanidins is exactly the opposite. Conclusions: Proanthocyanidins can effectively alleviate fluoride-induced liver injury, potentially by regulating the mTOR signaling pathway, autophagy, and apoptosis mechanisms. This study provides valuable insights into the protective effects of proanthocyanidins against fluoride-induced hepatic damage and offers a theoretical basis for further research in this field. Full article

This study investigates two-sided pulsed-periodic laser welding of three-layer metal–polymer–metal (MPM) composite sheets composed of galvanized dual-phase steel (DPK 30/50+ZE) as outer layers and a polypropylene–polyethylene (PP–PE) core. Welding was performed using a Rofin StarWeld Performance pulsed Nd:YAG laser with controlled parameters: pulse energy (30–32 J), duration (6–8 ms), and frequency (up to 1 Hz). High-quality welds were achieved with penetration depths reaching 70% of the outer metal layer thickness and minimal defects. Microscopic analysis revealed distinct fusion and heat-affected zones (HAZ) with no evidence of cracks or porosity, indicating stable thermal conditions. Mechanical testing showed that the welded joints attained a tensile strength of approximately 470 MPa, about 80% of the ultimate tensile strength of the base metal, with an average elongation of 0.6 mm. These results confirm the structural integrity of the joints. The observed weld morphology and microstructural features suggest that thermal conditions during welding significantly affect joint quality and HAZ formation. The study demonstrates that strong, defect-free joints can be produced using basic beam-shaping optics and outlines a pathway for further improvement through the integration of diffractive optical elements (DOEs) to enhance spatial-energy control in multilayer structures. Full article

Pea peptides (PPs), as organic compounds, exhibit a variety of biological functions that make them useful for both the prevention and treatment of metabolic disorders. This study focused on how PPs modified by steam explosion (SE-PP) may help to treat mice with high-fat diet (HFD)-mediated glucose metabolism disorders. The experimental results indicate that both the 100 mg/kg BW SE-PP (SE-PPL group) and 400 mg/kg BW SE-PP (SE-PPH group) experienced substantial decreases in body weight, epididymal and inguinal fat mass, and blood glucose levels of obese mice (notably, the body weight of the SE-PPH group was decreased by 33.13% when compared with that of the HFD group (p < 0.05)). By stimulating the IRS-1/PI3K/AKT signaling system, SE-PP controlled glucose metabolism disorder in adipose tissue, while also inhibiting the TLR4/MYD88/NF-κB pathway to reduce inflammation. Furthermore, SE-PP restored the diversity of the gut microbiota destroyed by HFD. SE-PPH increased the Bacteroidetes/Firmicutes ratio from 0.042 to 0.26 (p < 0.05), which is a key indicator of microbiota balance. In addition, SE-PP enhanced the synthesis of short-chain fatty acids (SCFAs) such as isovalerate, propionate, and acetate, which are essential for maintaining intestinal homeostasis and improving metabolic health (supplementation of SE-PPH increased the levels of total SCFAs by 49.87% in obese mice (p < 0.05)). Full article

Sweet potato stems and leaves (SPSL) are rich in bioactive polyphenols, yet their utilization remains underexplored. This study established an efficient method for SPSL polyphenol enrichment using macroporous resins, with UHPLC-QE-MS/MS characterization of the purified polyphenols (PP) and subsequent evaluation of anti-inflammatory activity. The results showed that NKA-II resin demonstrated the best purification effect on SPSL polyphenols among the six tested resins. The optimal enrichment procedure of NKA-II resin was as follows: loading sample pH 3.0, 4.48 mg CAE/mL concentration, and 80% ethanol (v/v) eluent. A total of 19 major compounds were characterized in PP, including 12 phenolic acids and seven flavonoids, with a polyphenol purity of 75.70%. PP pretreatment (100 and 500 μg/mL) significantly inhibited LPS-induced release of NO (by 40.62% and 68.61%), IL-1β (by 40.07% and 68.34%), IL-6 (by 40.63% and 52.41%), and TNF-α (by 52.29% and 73.76%) compared to the LPS group (p < 0.05), demonstrating potent anti-inflammatory effects. Western blot analysis revealed that PP exerted anti-inflammatory effects by inhibiting the NF-κB (via suppression of IκBα phosphorylation/degradation and blockade of p65 nuclear translocation) and MAPK (via inhibition of p38, ERK, and JNK phosphorylation) signaling pathways. These findings support the utilization of this agricultural by-product in functional food development, particularly as a source of natural anti-inflammatory compounds for dietary supplements or fortified beverages. Full article

As a key economic tree in southern China, Camellia oleifera faces severe yield losses under drought. Grafting onto drought-tolerant rootstocks offers a potential mitigation strategy. To elucidate the impact of rootstocks on the drought resistance of the superior Camellia oleifera Abel. cultivar “Xianglin 210”, grafted seedlings with five scion–rootstock combinations, were subjected to gradient drought stress. Key physiological and biochemical indices related to photosynthesis, antioxidant enzymes, and osmotic adjustment were measured. Drought resistance was comprehensively evaluated using membership function analysis, and the expression of stress-responsive genes was quantified via quantitative real-time PCR (qRT-PCR). The results demonstrated that under drought stress, (1) stomatal conductance (Gs) decreased by 31.2–48.7%, while instantaneous water use efficiency (WUE) increased by 18.5–35.4%; (2) proline (Pro) and soluble sugars (SS) accumulated significantly, with increases of 2.3–4.1-fold and 1.8–3.2-fold, respectively; (3) activities of antioxidant enzymes were enhanced by 56–127%, mitigating oxidative damage; (4) membership function analysis ranked drought resistance as follows: Xianglin 27 (0.812) > Guangxi Superior Germplasm (0.698) > C. yuhsienensis (0.654) > Hunan Superior Germplasm (0.591) > Xianglin 1 (0.523); (5) qRT-PCR revealed significant upregulation of ABA signaling pathway genes (CoPYL6, CoPP2C75/51/24/26, CoSnRK2.8, and CoABI5) and transcription factors (CoLHY and CoWRKY70), indicating activation of drought-responsive regulatory networks. These findings provide a theoretical foundation for selecting drought-tolerant rootstocks and optimizing cultivation practices in Camellia oleifera, and provide practical criteria for selecting drought-tolerant rootstocks, facilitating sustainable Camellia oleifera cultivation in water-limited regions. Full article

The peach landrace ‘Liuyefeitao’ exhibits the unique reproductive trait of self-compatibility combined with cross-incompatibility, contrasting with typical Prunus species in this way. In preliminary studies involving controlled pollination assays, we showed complete pollen tube arrest in cross-pollinated styles, whereas self-pollination enabled full tube elongation. S-genotyping identified a homozygous S₂S₂ genotype with intact S₂-RNase but a truncated PpSFB2 due to a frameshift mutation. Transcriptome profiling of the styles revealed 7937 differentially expressed genes (DEGs) between self- and cross-pollination treatments, with significant enrichment in plant MAPK signaling, plant–pathogen interactions, and plant hormone signaling transduction pathways (|Fold Change| ≥ 2, FDR < 0.01). Notably, PpSLFL3 (a pollen F-box gene) showed down-regulation in cross-pollinated styles, as validated by means of qRT-PCR. Protein interaction assays revealed direct binding between PpSLFL3 and S₂-RNase via Y2H and BiFC analysis, suggesting its role in mediating SCF complex-dependent degradation. We propose that insufficient PpSLFL3 expression during cross-pollination disrupts SCF ubiquitin ligase complex-mediated degradation of non-self S₂-RNase, leading to the toxic degradation of RNA in pollen tubes by S₂-RNase. This mechanism is mechanistically similar to unilateral reproductive barriers in Solanaceae but represents a novel regulatory module in Rosaceae. Our findings provide critical insights into the evolution of cross-incompatibility systems and molecular breeding strategies for Prunus species. Full article

We present a highly sensitive and selective gas sensor based on an advanced silicon-on-insulator tunnel field-effect transistor (SOI-TFET) architecture, enhanced through the integration of customized conducting polymers. In this design, traditional metal gates are replaced with distinct functional polymers—PPP-TOS/AcCN, PP-TOS/AcCN, PP-FE(CN)₆³⁻/H₂O, PPP-TCNQ-TOS/AcCN, and PPP-ClO₄/AcCN—which enable precise molecular recognition and discrimination of various target gases. To further enhance sensitivity, the device employs an oppositely doped source region, significantly improving gate control and promoting stronger band-to-band tunneling. This structural modification amplifies sensing signals and improves noise immunity, allowing reliable detection at trace concentrations. Additionally, optimization of the subthreshold swing contributes to faster switching and response times. Thermal stability is addressed by embedding a P-type buffer layer within the buried oxide, which increases thermal conductivity and reduces lattice temperature, further stabilizing device performance. Experimental results demonstrate that the proposed sensor outperforms conventional SOI-TFET designs, exhibiting superior sensitivity and selectivity toward analytes such as methanol, chloroform, isopropanol, and hexane. Beyond gas sensing, the unique polymer-functionalized gate design enables integration of microbial biosensing capabilities, making the platform highly versatile for biochemical detection. This work offers a promising pathway toward ultra-sensitive, low-power sensing technologies for environmental monitoring, industrial safety, and medical diagnostics. Full article

The development of anode-free sodium metal batteries (AFSMBs) offers a promising pathway to achieve ultrahigh energy density and cost efficiency inherent to conventional sodium ion/metal batteries. However, irreversible Na plating/stripping and dendritic growth remain critical barriers. Herein, we demonstrate that separator engineering is a pivotal strategy for stabilizing AFSMBs. Through systematic evaluation of four separators—2500 separator (PP), 2325 separator (PP/PE/PP), glass fiber (GF), and an Al₂O₃-coated PE membrane, we reveal that the Al₂O₃-coated separator uniquely enables exceptional interfacial kinetics and morphological control. Na||Na symmetric cells with Al₂O₃ coated separator exhibit ultralow polarization (4.5 mV) and the highest exchange current density (1.77 × 10⁻² mA cm⁻²), while the anode-free AlC-NFPP full cells retain 91.6% capacity after 150 cycles at 2C. Specifically, the Al₂O₃ coating homogenizes Na⁺ flux, promotes dense and planar Na deposition, and facilitates near-complete stripping with minimal “dead Na”. This work establishes ceramic-functionalized separators as essential enablers of practical high-energy AFSMBs. Full article

Background: Heat therapy (HT) and electroacupuncture (EA) are widely utilized pain relief methods, but the analgesic mechanisms of their combined application remain unclear. Methods: In acetic acid (AA)-induced writhing test and complete Freund’s adjuvant (CFA)-induced inflammatory pain tests, mice received one of three treatments: EA at bilateral ST36, HT via a 45 °C heating pad, or the combination (EA + HT). To probe underlying pathways, separate groups were pretreated with caffeine, DPCPX (a selective adenosine A₁ receptor antagonist), or naloxone (an opioid receptor antagonist). Spinal expression of glial fibrillary acidic protein (GFAP) and phosphorylated p38 (p-p38) was examined by Western blot and immunofluorescence. Results: Both EA and HT individually reduced AA-induced writhing, with the combination (EA + HT) exhibiting the greatest analgesic effect. EA’s analgesic effect was reversed by caffeine and DPCPX and partially by naloxone, while HT’s effect was reversed by caffeine and DPCPX but was unaffected by naloxone. AA injection elevated spinal p-p38 and GFAP expression, which were attenuated by either EA or HT, with the most substantial suppression observed in the EA + HT group. In the CFA model, both treatments alleviated mechanical allodynia, while the combined treatment resulted in significantly greater analgesia compared to either treatment alone. Conclusions: EA combined with HT synergistically enhances analgesia in both AA and CFA pain models, accompanied by reduced spinal inflammation and astrocyte activation. EA’s analgesic effects appear to involve adenosine A₁ receptor pathways and, to a lesser extent, opioid receptor mechanisms, whereas HT’s effects involve adenosine A₁ receptor pathways. Full article

Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), which leads to alveolar bone destruction and systemic inflammation. Emerging evidence suggests that probiotics may mitigate periodontal pathology. To systematically evaluate the alleviative effects and mechanisms of different forms of probiotics, including live bacteria and postbiotics, on periodontitis, we first screened and identified Ligilactobacillus salivarius CCFM1332 (L. salivarius CCFM1332) through in vitro antibacterial and anti-biofilm activity assays. Subsequently, we investigated its therapeutic potential in a rat model of experimental periodontitis. The results demonstrated that both live L. salivarius CCFM1332 (PL) and its postbiotics (PP) significantly reduced the gingival index (GI) and probing depth (PD) in rats, while suppressing oral colonization of P. gingivalis. Serum pro-inflammatory cytokine levels were differentially modulated: the PL group exhibited reductions in interleukin-17A (IL-17A), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by 39.31% (p < 0.01), 17.26% (p < 0.05), and 14.74% (p < 0.05), respectively, whereas the PP group showed decreases of 34.79% (p < 0.05), 29.85% (p < 0.01), and 19.74% (p < 0.05). Micro-computed tomography (Micro-CT) analysis demonstrated that compared to the periodontitis model group (PM), the PL group significantly reduced alveolar bone loss (ABL) by 30.1% (p < 0.05) and increased bone volume fraction (BV/TV) by 49.5% (p < 0.01). In contrast, while the PP group similarly decreased ABL by 32.7% (p < 0.05), it resulted in a 40.4% improvement in BV/TV (p > 0.05). Histological assessments via hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining confirmed that both the PL group and the PP group alleviated structural damage to alveolar bone-supporting tissues and reduced osteoclast-positive cell counts. This study suggests that live L. salivarius CCFM1332 and its postbiotics reduce alveolar bone resorption and attachment loss in rats through antibacterial and anti-inflammatory pathways, thereby alleviating periodontal inflammation in rats. Full article

The phosphofructokinase (PFK) gene family plays a pivotal role in glycolysis and energy metabolism in plants. This study aimed to systematically characterize the PFK gene family in Arabidopsis thaliana at the genome-wide level and to investigate the function of AtPFK2 (ATP-dependent phosphofructokinase 2) in response to salt and drought stress. Through bioinformatics analysis, 11 AtPFK genes were identified. Phylogenetic analysis revealed that these PFK genes can be classified into two subfamilies: PFK and PFP. Notably, AtPFK2 possesses a unique structure, containing only a single intron, and its promoter is enriched with stress- and hormone-responsive elements, such as ABRE and MBS. T-DNA insertion mutants (pfk2) exhibited slightly shorter roots but slightly higher fresh weight under stress conditions, whereas Arabidopsis lines AtPFK2-overexpressing (OE-PFK2) showed increased stress sensitivity, with inhibited root and leaf growth, leaf wilting, reduced malondialdehyde and chlorophyll content, and enhanced accumulation of proline and soluble sugars. Weighted gene co-expression network analysis (WGCNA) identified 14 stress-related modules, from which six core genes—LBD41, TRP3, PP2-A3, SAUR10, IAA6, and JAZ1—were selected. These genes are involved in glycine metabolism and plant hormone signaling. The results of this study indicate that AtPFK2 mediates stress responses by regulating osmoregulatory substances and hormone signaling pathways, offering new insights into the mechanisms of stress resistance in crops. Full article

Background/Objectives: The physiological activation of cytotoxic CD8^pos T cells (CTLs) relies on the engagement of the TCR/CD3 complex with cognate peptide-HLA class I (pHLA-I) on target cells, triggering cell lysis with appropriate cytokine release and minimized off-target toxicity. In contrast, current immunotherapies for CD19-expressing hematological malignancies, such as chimeric antigen receptor (CAR) T cells and bispecific T cell engagers (BiTEs), bypass TCR/pHLA interactions, resulting in CTL hyperactivation and excessive cytokine release, which frequently cause severe immune-related adverse events (irAEs). Thus, there is a pressing need for T cell-based therapies that preserve physiological activation while maintaining antitumor efficacy. Methods: To address this, we developed CD19-ReTARG^TPR, a novel fusion protein consisting of the immunodominant cytomegalovirus (CMV) pp65-derived peptide TPRVTGGAM (TPR) covalently presented by a soluble HLA-B*07:02/β2-microglobulin complex fused to a high-affinity CD19-targeting Fab antibody fragment. The treatment of CD19-expressing cancer cells with CD19-ReTARG^TPR makes them recognizable for pre-existing anti-CMV_pp65 CTLs via physiological TCR-pHLA engagement. Results: Our preclinical data demonstrate that CD19-ReTARG^TPR efficiently redirects anti-CMV CTLs to eliminate CD19-expressing cancer cells, including both established cell lines and primary chronic lymphocytic leukemia (CLL) cells. Unlike CD19-directed CAR T cells or the CD19/CD3 BiTE blinatumomab, CD19-ReTARG^TPR mediated robust cytotoxic activity without triggering supraphysiological cytokine release. Importantly, this approach retained efficacy even against cancer cells with low CD19 expression. Conclusions: In summary, we provide a robust proof-of-concept study and show that CD19-ReTARG^TPR offers a promising alternative strategy for T cell redirection, enabling the selective and effective killing of CD19-expressing malignancies while minimizing cytokine-driven toxicities through physiological CTL activation pathways. Full article

Saccharomyces cerevisiae often undergoes strain degeneration during industrial serial subculturing, though this phenomenon remains understudied. This study first conducted strain screening and biological characterization through TTC (2,3,5-triphenyltetrazolium chloride) colorimetric assays, Durham tube fermentation gas production tests, and WL medium (Wallerstein Laboratory medium) cultivation. Subsequently, the changes in intergenerational biological traits after serial subculturing were investigated. Finally, transcriptomic analysis was employed to examine differential gene expression under high-glucose stress during continuous subculturing. The experimental results demonstrated that: (1) The S. cerevisiae QDSK310-Z-07 (GenBank: PP663884), isolated from farm soil, exhibited robust growth within a temperature range of 24–36 °C, with optimal growth observed at 28 °C. It thrived in a pH range of 4–5.5 and efficiently utilized various carbon and nitrogen sources; (2) After serial subculturing, the strain’s ethanol production capacity and fermentation rate partially declined and then stabilized, while maintaining strong tolerance to high ethanol concentrations and hyperosmotic stress; (3) Transcriptomic analysis revealed significant differential expression of genes related to lipid metabolism, amino acid metabolism, and other pathways under high-glucose stress following continuous subculturing. These findings elucidate the biological trait variations in S. cerevisiae during serial subculturing and provide key metabolic regulation candidate targets for its long-term adaptive evolution under high-glucose stress. Full article

Plastic waste is currently a major concern in Romania due to the annual increase in quantities generated from anthropogenic and industrial activities, especially from end-of-life vehicles (ELVs), and the need to reduce environmental impact. This study investigates an alternative valorization route for polypropylene (PP) and polyethylene (PE) plastic waste through microwave-assisted pyrolysis, aiming to maximize conversion into gaseous products, particularly hydrogen-rich gas. A monomode microwave reactor was employed, using layered configurations of plastic feedstock, silicon carbide as a microwave susceptor, and activated carbon as a catalyst. The influence of catalyst loading, reactor configuration, and plastic type was assessed through systematic experiments. Results showed that technical-grade PP, under optimal conditions, yielded up to 81.4 wt.% gas with a hydrogen concentration of 45.2 vol.% and a hydrogen efficiency of 44.8 g/g. In contrast, PE and mixed PP + PE waste displayed lower hydrogen performance, particularly when containing inorganic fillers. For all types of plastics studied, the gaseous fractions obtained have a high calorific value (46,941–55,087 kJ/kg) and at the same time low specific CO₂ emissions (4.4–6.1 × 10⁻⁵ kg CO₂/kJ), which makes these fuels very efficient and have a low carbon footprint. Comparative tests using conventional heating revealed significantly lower hydrogen yields (4.77 vs. 19.7 mmol/g plastic). These findings highlight the potential of microwave-assisted pyrolysis as an efficient method for transforming ELV-derived plastic waste into energy carriers, offering a pathway toward low-carbon, resource-efficient waste management. Full article

Microplastics (MPs) have emerged as a critical environmental challenge in China’s aquatic ecosystems, driven by rapid industrialization and population growth. This review synthesizes recent findings on the abundance, morphology, and polymer types of MPs in China’s freshwater systems (rivers, lakes, reservoirs) and coastal marine environments. Spatial analysis reveals significant variability in MP abundance, ranging from 0.1 items/L in Tibet’s Lalu Wetland to 30.8 items/L in Beijing’s Qinghe River, with polypropylene (PP) and polyethylene (PE) dominating polymer profiles. Coastal regions exhibit distinct contamination patterns, with the Yellow Sea (5.3 ± 2.0 items/L) and the South China Sea (180 ± 80 items/m³) showing the highest MP loads, primarily as fibers and fragments. Fluvial transport, atmospheric deposition, and coastal anthropogenic activities (e.g., fisheries, tourism) are identified as major pathways for marine MP influx. Secondary MPs from degraded plastics and primary MPs from industrial/domestic effluents pose synergistic risks through the adsorption of heavy metals and organic pollutants. Human exposure routes—ingestion, inhalation, and dermal contact—are linked to inflammatory, metabolic, and carcinogenic health outcomes. Policy interventions, including bans on microbeads and non-degradable plastics, demonstrate progress in pollution mitigation. This work underscores the urgency of integrated source control, advanced wastewater treatment, and transboundary monitoring to address MP contamination in aquatic ecosystems. Full article