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The Ni/Al2O3 interface bears the load transfer and energy dissipation, which determines the service performance of the composite materials. In this study, three distinct vacancy-defect-modified interface models (D1, D2, and D3, corresponding to vacancies in the first, second, and third layers of the Ni substrate surface, respectively) were constructed to systematically investigate the regulatory mechanism of vacancies on interfacial stability. The underlying mechanism of vacancy-enhanced interfacial stability was elucidated from both atomic-scale structural and electronic property perspectives. The results demonstrate that the D1, D2, and D3 structures increase the adhesion work of the interface by 2.0%, 6.7%, and 0.3%, respectively. This enhancement effect mainly stems from vacancy-induced atomic relaxation at the interface, which optimizes the equilibrium interfacial spacing and effectively releases residual strain energy. Further electronic structure analysis reveals a notable increase in charge density at the vacancy-modified interface (particularly in the D2 structure), indicating that vacancy defects promote charge transfer and redistribution by altering local electron distribution. More importantly, the bonding strength of the interface exhibits a positive correlation with electron orbital hybridization intensity, where stronger s-, p-, and d-orbit hybridization directly leads to a more stable interface. These findings provide atomic- and electronic-scale insights into the mechanistic role of vacancy defects in governing bonding at the Ni/Al2O3 interface.

Acute lung injury (ALI) is a life-threatening disease that has received considerable critical attention in the field of intensive care. This study aimed to explore the role and mechanism of vitamin K2 (VK2) in ALI. Intraperitoneal injection of 7 mg/kg LPS was used to induce ALI in mice, and VK2 injection was intragastrically administered with the dose of 0.2 and 15 mg/kg. We found that VK2 improved the pulmonary pathology, reduced myeloperoxidase (MPO) activity and levels of TNF-α and IL-6, and boosted the level of IL-10 of mice with ALI. Moreover, VK2 played a significant part in apoptosis by downregulating and upregulating Caspase-3 and Bcl-2 expressions, respectively. As for further mechanism exploration, we found that VK2 inhibited P38 MAPK signaling. Our results also showed that VK2 inhibited ferroptosis, which manifested by reducing malondialdehyde (MDA) and iron levels, increasing glutathione (GSH) level, and upregulated and downregulated glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) expressions, respectively. In addition, VK2 also inhibited elastin degradation by reducing levels of uncarboxylated matrix Gla protein (uc-MGP) and desmosine (DES). Overall, VK2 robustly alleviated ALI by inhibiting LPS-induced inflammation, apoptosis, ferroptosis, and elastin degradation, making it a potential novel therapeutic candidate for ALI.

The ciliate Tetrahymena thermophila has been a powerful model system for molecular and cellular biology. However, some investigations have been limited due to the incomplete closure and sequencing of the macronuclear genome assembly, which for many years has been stalled at 1,158 scaffolds, with large sections of unknown sequences (available in Tetrahymena Genome Database, TGD, http://ciliate.org/ ). Here we completed the first chromosome-level Tetrahymena macronuclear genome assembly, with approximately 300× long Single Molecule, Real-Time reads of the wild-type SB210 cells—the reference strain for the initial macronuclear genome sequencing project. All 181 chromosomes were capped with two telomeres and gaps were entirely closed. The completed genome shows significant improvements over the current assembly (TGD 2014) in both chromosome structure and sequence integrity. The majority of previously identified gene models shown in TGD were retained, with the addition of 36 new genes and 883 genes with modified gene models. The new genome and annotation were incorporated into TGD. This new genome allows for pursuit in some underexplored areas that were far more challenging previously; two of them, genome scrambling and chromosomal copy number, were investigated in this study. We expect that the completed macronuclear genome will facilitate many studies in Tetrahymena biology, as well as multiple lines of research in other eukaryotes.

Stroke is the second leading cause of death globally. Oxidative stress plays a critical role in the development of stroke. The Oxidative Balance Score (OBS) is a tool used to assess the combined impact of diet and lifestyle on the body’s antioxidant capacity. The study included stroke survivors from the National Health and Nutrition Examination Survey (1999–2018), with a total of 1,781 participants and a median follow-up duration of 6.5 years, during which 786 participants (39.59%) died. The relationship between OBS and all-cause mortality was assessed using the Cox proportional hazards model. The results indicated that individuals in higher OBS quartiles had lower mortality rates. Specifically, patients in the fourth quartile had a 41% reduced risk of all-cause mortality compared to those in the first quartile (HR = 0.59, 95% CI = 0.42–0.84, p  = 0.003). Restricted cubic spline analysis revealed a linear inverse relationship between OBS and all-cause mortality. Subgroup analysis further demonstrated that the inverse association persisted across various population subgroups. Overall, our study suggests that higher levels of OBS can reduce the risk of all-cause mortality in stroke survivors and provides new evidence for their diet and lifestyle.

Background Glutathione S-transferases (GSTs) are large and multifunctional proteases that play an important role in detoxification, protection against biotic and abiotic stresses, and secondary metabolite transportation which is essential for plant growth and development. However, there is limited research on the identification and function of NtGST s. Results This study uses K326 and other six tobacco varieties (Hongda, HG, GDH11, Va116, VG, and GDH88) as materials to conduct comprehensive genome-wide identification and functional characterization of the GST gene in tobacco. A total of 59 NtGST s were identified and classified into seven subfamilies via the whole-genome sequence analysis, with the Tau type serving as the major subfamily. The NtGST s in the same branch of the evolutionary tree had similar exon/intron structure and motif constitution. There were more than 42 collinear blocks between tobacco and pepper, tomato, and potato, indicating high homology conservation between them. Twelve segmental duplicated gene pairs and one tandem duplication may have had a substantial impact on the evolution and expansion of the tobacco GST gene family. The RT-qPCR results showed that the expression patterns of NtGST s varied significantly among tissues, varieties, and multiple abiotic stresses, suggesting that NtGST genes may widely respond to various abiotic stresses and hormones in tobacco, including NtGSTF4 , NtGSTL1 , NtGSTZ1 , and NtGSTU40 . Conclusions This study provides a comprehensive analysis of the NtGST gene family, including structures and functions. Many NtGSTs play a critical regulatory role in tobacco growth and development, and responses to abiotic stresses. These findings offer novel and valuable insights for understanding the biological function of NtGSTs and the reference materials for cultivating highly resistant varieties and enhancing the yield and quality of crops.

Background Interstitial lung disease, a common extra-articular complication of connective tissue disease, is characterized by progressive and irreversible pulmonary inflammation and fibrosis, which causes significant mortality. IL-22 shows a potential in regulating chronic inflammation and possibly plays an anti-fibrotic role by protecting epithelial cells. However, the detailed effects and underlying mechanisms are still unclear. In this study, we explored the impact of IL-22 on pulmonary fibrosis both in vivo and in vitro . Methods To induce pulmonary fibrosis, wild-type mice and IL-22 knockout mice were intratracheally injected with bleomycin followed by treatments with recombinant IL-22 or IL-17A neutralizing antibody. We investigated the role of IL-22 on bleomycin-induced pulmonary fibrosis and the mechanism in the possible interaction between IL-22 and IL-17A. Fibrosis-related genes were detected using RT-qPCR, western blot, and immunofluorescence. Inflammatory and fibrotic changes were assessed based on histological features. We also used A549 human alveolar epithelial cells, NIH/3T3 mouse fibroblast cells, and primary mouse lung fibroblasts to study the impact of IL-22 on fibrosis in vitro . Results IL-22 knockout mice showed aggravated pulmonary fibrosis compared with wild-type mice, and injection of recombinant IL-22 decreased the severe fibrotic manifestations in IL-22 knockout mice. In cell culture assays, IL-22 decreased protein levels of Collagen I in A549 cells, NIH/3T3 cells, and primary mouse lung fibroblasts. IL-22 also reduced the protein level of Collagen I in NIH/3T3 cells which were co-cultured with T cells. Mechanistically, IL-22 reduced the Th17 cell proportion and IL-17A mRNA level in lung tissues, and treatment with an IL-17A neutralizing antibody alleviated the severe pulmonary fibrosis in IL-22 knockout mice. The IL-17A neutralizing antibody also reduced Collagen I expression in NIH/3T3 cells in vitro . Knockdown of IL-17A with siRNAs or administration of IL-22 in NIH/3T3 cells and MLFs decreased expression of Collagen I, an effect blocked by concurrent use of recombinant IL-17A. Conclusions IL-22 mediated an anti-fibrogenesis effect in the bleomycin-induced pulmonary fibrosis model and this effect was associated with inhibition of IL-17A.

Background As transcription factors, the TCP genes are considered to be promising targets for crop enhancement for their responses to abiotic stresses. However, information on the systematic characterization and functional expression profiles under abiotic stress of TCP s in Tartary buckwheat ( Fagopyrum tataricum (L.) Gaertn.) is limited. Results In this study, we identified 26 FtTCP s and named them according to their position on the chromosomes. Phylogenetic tree, gene structure, duplication events, and cis-acting elements were further studied and syntenic analysis was conducted to explore the bioinformatic traits of the FtTCP gene family. Subsequently, 12 FtTCP genes were selected for expression analysis under cold, dark, heat, salt, UV, and waterlogging (WL) treatments by qRT-PCR. The spatio-temporal specificity, correlation analysis of gene expression levels and interaction network prediction revealed the potential function of FtTCP15 and FtTCP18 in response to abiotic stresses. Moreover, subcellular localization confirmed that FtTCP15 and FtTCP18 localized in the nucleus function as transcription factors. Conclusions In this research, 26 TCP genes were identified in Tartary buckwheat, and their structures and functions have been systematically explored. Our results reveal that the FtTCP15 and FtTCP18 have special cis-elements in response to abiotic stress and conserved nature in evolution, indicating they could be promising candidates for further functional verification under multiple abiotic stresses.

B-cell lymphoma/leukemia gene-2(Bcl-2) protein family known for regulating cell cycle arrest and subsequent cell death is highly expressed in a variety of cancers. Among them, the Bcl-xL and Bcl-2 are two essential proteins in the Bcl-2 family. In the present work, the differences in binding modes as between the two proteins and two ligands ABT-263/43b were investigated and compared. And the computational alanine scanning combined with the recently developed interaction entropy (AS-IE) method was employed for predicting their binding free energies and finding those amino acids that were more critical during the binding process. The result showed that the binding free energy calculated by the AS-IE method was more in line with experimental values than the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method. Besides, no significant difference was found between Bcl-xL and ABT-263/43b in the binding free energy, which Bcl-xL showed slightly weaker binding free energy to 43b because of the fewer number of key residues with interactions. Nonetheless, compared with the Bcl-2 and 43b complex, the Bcl-2 and ABT-263 system had greater number of key residues interacting with ABT-263, in particular, contribute favorably, resulting in a stronger binding ability for the Bcl-2 and ABT-263 systems. The van der Waals and hydrogen bond contributions were significant in the four protein–ligand complexes. Overall, Tyr108 was found to be the common key residues in the Bcl-xL–ligand complex, while Tyr105, Glu100, and Glu143 were established as the common key residue in the Bcl-2–ligand systems. We hope that the predicted hot spot residues and their energy distributions can guide the design of peptide and small-molecule drugs targeting Bcl-xL and Bcl-2.

Neoadjuvant immunochemotherapy is increasingly used for resectable locally advanced gastric cancer (LAGC) and gastroesophageal junction (EGJ) adenocarcinoma, yet the optimal chemotherapy backbone for PD-1 blockade remains unclear. We compared neoadjuvant PD-1 inhibitor plus S-1+oxaliplatin (SOX) versus PD-1 inhibitor plus 5-FU+oxaliplatin+Docetaxel+Leucovorin (FLOT) in a real-world cohort. This single-center retrospective study included patients with resectable, HER2-negative LAGC/EGJ adenocarcinoma (cT3-4b, any N+, M0; ECOG 0-1) treated between July 2020 and July 2025. Patients received neoadjuvant PD-1 inhibitor plus SOX or PD-1 inhibitor plus FLOT (3-5 cycles) followed by D2 gastrectomy. The primary endpoint was pathological complete response (pCR). Secondary endpoints included major pathological response (MPR), radiologic response (RECIST v1.1), perioperative outcomes, treatment-related adverse events (CTCAE v5.0), recurrence-free survival (RFS), and overall survival (OS). Survival was analyzed using Kaplan-Meier methods and Cox proportional hazards models. Overall, 247 patients were enrolled (PD-1+SOX, n=141; PD-1+FLOT, n=106) with comparable baseline characteristics. Radiologic outcomes were similar between groups (ORR: 70.92% vs 66.98%, p=0.507; DCR: 87.23% vs 85.85%, p=0.752). Pathological responses did not differ significantly (pCR: 20.57% vs 16.98%, p=0.477; MPR: 37.59% vs 31.13%, p=0.292). Any-grade treatment-related adverse events occurred in 67.38% and 75.47% of patients, and grade ≥3 events in 19.15% and 26.42%, respectively; no treatment-related deaths occurred. R0 resection rates were high (100% vs 99.06%). Operative time and estimated blood loss were higher in the PD-1+FLOT group (p=0.010 and p=0.040), while postoperative complication rates were comparable. With median follow-up of 21 months (12-52) and 20 months (10-46), there were no significant differences in OS (HR 1.155, 95% CI 0.624-2.138) or RFS (HR 0.805, 95% CI 0.461-1.405). In multivariable analyses, non-MPR was an independent risk factor for both OS and RFS. Neoadjuvant PD-1 inhibitor plus SOX and plus FLOT yielded comparable response rates, survival outcomes, and safety profiles in patients with resectable LAGC/EGJ adenocarcinoma. PD-1+SOX was associated with less operative burden, and MPR remained independently associated with OS and RFS, supporting its value for risk stratification and treatment optimization.

Background Nicotine exhibits positive heterosis, and through its utilization, new tobacco varieties with ideal nicotine content have been bred. However, the potential mechanism underlying the increased transport and nicotine accumulation capacity in hybrids remain poorly understood. Results The purpose of this study was to reveal the regulatory role of the key gene NtGSTU10 , which was identified during the early stages of nicotine heterosis. NtGSTU10 -over expression lines were created through genetic transformation, and the nicotinic content, transport coefficient, and heterosis of NtGSTU10 -over expression lines and wild-type tobacco plants were compared. The results suggested that the nicotine content in the leaves of V×OB7 (The over expression hybrids were produced by crossing Va116 as the female parent with OB7 as the male parent.) and V×OB12 (The over expression hybrids were produced by crossing Va116 as the female parent with OB12 as the male parent.) was significantly higher than that of the wild-type hybrid (V×B). Compared to the V×B, the nicotine transport coefficients of V×OB7 and V×OB12 were significantly increased by 39.50% and 40.67%, respectively; and nicotine heterosis was significantly increased by 120.07% and 127.59%, respectively. Further analysis showed that overexpression of the NtGSTU10 gene could result in up-regulated expression of genes related to nicotine synthesis ( AOC , QS , ODC , and PAO ) and transport ( ABCB1 , ABCC1 , and ABCC2 ), as well as down-regulation of negative regulatory factors ( ERF1 , ETR , and JAZ ). Conclusions The results indicated that overexpression of the NtGSTU10 gene promotes the synthesis and transport metabolism of nicotine in tobacco, positively contributing to increased nicotine content in hybrids. The research findings provide a molecular basis for regulating the nicotine transport and accumulation in hybrids, and also provide genetic resources for the targeted cultivation of new tobacco varieties with suitable nicotine content.