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Abstract Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI) approved for patients with EGFR T790M resistance mutations as first- or second-line treatment of EGFR-positive patients. Resistance to Osimertinib will inevitably develop, and the underlying mechanisms are largely unknown. In this study, we discovered that acquired resistance to Osimertinib is associated with abnormal DNA damage response (DDR) in lung adenocarcinoma cells. We discovered that the polycomb protein Lethal(3) Malignant Brain Tumor-Like Protein 1 (L3MBTL1) regulates chromatin structure, thereby contributing to DDR and Osimertinib resistance. EGFR oncogene inhibition reduced L3MBTL1 ubiquitination while stabilizing its expression in Osimertinib-resistant cells. L3MBTL1 reduction and treatment with Osimertinib significantly inhibited DDR and proliferation of Osimertinib-resistant lung cancer cells in vitro and in vivo. L3MBTL1 binds throughout the genome and plays an important role in EGFR-TKI resistance. It also competes with 53BP1 for H4K20Me2 and inhibits the development of drug resistance in Osimertinib-resistant lung cancer cells in vitro and in vivo. Our findings suggest that L3MBTL1 inhibition is a novel approach to overcoming EGFR-TKI-acquired resistance.

The main challenge faced by spacecraft is the large temperature difference in its operating environment. Thermal control coatings prepared on spacecraft and instrument surfaces are currently the most efficient ways for heat dissipation and control. In this work, Al2O3-xTiO2 composite coatings with different TiO2 contents were prepared on 7075-Al alloy substrate by supersonic plasma spraying technology. The microstructure, phase composition, mechanical properties, thermal control properties, and corrosion resistances of the coatings were investigated. The raw stock feeds were mainly composed of α-Al2O3 and anatase TiO2, but the coatings were mainly γ-Al2O3 and rutile TiO2. The average Vickers microhardness of the coatings decreased from 1198.9 to 810.4 HV0.2 with the increase of TiO2 contents, but the elastic modulus increased from 158.5 to 244.3 GPa. The thermal control properties of the coatings were promoted with the growth of TiO2 contents, and the absorptance increased from 27.1 to 89.2% with the emittance from 83.7 to 86.5%. The corrosion potential and corrosion resistance of the coating gradually increased with TiO2 content due to its gradually improved hydrophobicity. This work broadens the application boundary of Al2O3-xTiO2 composite coating and provides an innovative idea for material selection of thermal control coatings.

Abstract Plasma membrane damage in vitrified oocytes is closely linked to mitochondrial dysfunction. However, the mechanism underlying mitochondria-regulated membrane stability is not elucidated. A growing body of evidence indicates that mitochondrial activity plays a pivotal role in cell adaptation. Since mitochondria work at a higher temperature than the constant external temperature of the cell, we hypothesize that suppressing mitochondrial activity would protect oocytes from extreme stimuli during vitrification. Here we show that metformin suppresses mitochondrial activity by reducing mitochondrial temperature. In addition, metformin affects the developmental potential of oocytes and improves the survival rate after vitrification. Transmission electron microscopy results show that mitochondrial abnormalities are markedly reduced in vitrified oocytes pretreated with metformin. Moreover, we find that metformin transiently inhibits mitochondrial activity. Interestingly, metformin pretreatment decreases cell membrane fluidity after vitrification. Furthermore, transcriptome results demonstrate that metformin pretreatment modulates the expression levels of genes involved in fatty acid elongation process, which is further verified by the increased long-chain saturated fatty acid contents in metformin-pretreated vitrified oocytes by lipidomic profile analysis. In summary, our study indicates that metformin alleviates cryoinjuries by reducing membrane fluidity via mitochondrial activity regulation.

Abstract Lung cancer is a leading cause of cancer-related mortality globally, with a dismal 5-year survival rate, particularly for Lung Adenocarcinoma (LUAD). Mechanical changes within the tumor microenvironment, such as extracellular matrix (ECM) remodeling and fibroblast activity, play pivotal roles in cancer progression and metastasis. However, the specific impact of the basement membrane (BM) on the mechanical characteristics of LUAD remains unclear. This study aims to identify BM genes influencing internal mechanical stress in tumors, elucidating their effects on LUAD metastasis and therapy resistance, and exploring strategies to counteract these effects. Using Matrigel overlay and Transwell assays, we found that mechanical stress, mimicked by matrix application, augmented LUAD cell migration and invasion, correlating with ECM alterations and activation of the epithelial-mesenchymal transition (EMT) pathway. Employing machine learning, we developed the SVM_Score model based on relevant BM genes, which accurately predicted LUAD patient prognosis and EMT propensity across multiple datasets. Lower SVM_Scores were associated with worse survival outcomes, elevated cancer-related pathways, increased Tumor Mutation Burden, and higher internal mechanical stress in LUAD tissues. Notably, the SVM_Score was closely linked to COL5A1 expression in myofibroblasts, a key marker of mechanical stress. High COL5A1 expression from myofibroblasts promoted tumor invasiveness and EMT pathway activation in LUAD cells. Additionally, treatment with Sorafenib, which targets COL5A1 secretion, attenuated the tumor-promoting effects of myofibroblast-derived COL5A1, inhibiting LUAD cell proliferation, migration, and enhancing chemosensitivity. In conclusion, this study elucidates the complex interplay between mechanical stress, ECM alterations, and LUAD progression. The SVM_Score emerges as a robust prognostic tool reflecting tumor mechanical characteristics, while Sorafenib intervention targeting COL5A1 secretion presents a promising therapeutic strategy to mitigate LUAD aggressiveness. These findings deepen our understanding of the biomechanical aspects of LUAD and offer insights for future research and clinical applications.

Abstract Background Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs. Methods This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively. Results Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively. Conclusion Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted. Trial registration NCT04507906 August 11, 2020.

This experiment aimed to evaluate the impact of dietary hydroxyproline (Hyp) supplementation on the muscle quality of juvenile Pacific white shrimp (Litopenaeus vannamei) fed a low fishmeal diet. Six formulated diets included one high fishmeal (HF; 25% fishmeal content) and five low fishmeal diets (10% fishmeal content) with 0%, 0.2%, 0.4%, 0.6% and 0.8% Hyp (LF0, LF2, LF4, LF6 and LF8, respectively). Each diet was assigned to four replicates, and 40 shrimp (0.32 ± 0.00 g) per replicate were fed four times a day for 8 weeks. Dietary Hyp supplementation had little effects on growth performance, but increased the contents of Hyp, prolyl 4-hydroxylases (P4Hs), and collagen. The meat yield, springiness, hardness, chewiness, and cohesiveness of muscle were the highest in the LF4 group among the low fishmeal groups (P < 0.05). Cooking loss and freezing loss of muscle were the lowest in the LF4 group (P

Abstract The identification of effective therapeutic targets plays a pivotal role in advancing cancer treatment outcomes. We employed a comprehensive pan-cancer analysis, complemented by experimental validation, to explore the potential of Nicotinamide N-methyltransferase (NNMT) as a promising therapeutic strategy for human cancers. By analyzing large-scale transcriptomic datasets across various cancer types, we consistently observed upregulated expression of NNMT. Furthermore, elevated NNMT expression correlated with inferior overall survival in multiple cancer cohorts, underscoring its significance as a prognostic biomarker. Additionally, we investigated the relationship between NNMT expression and the tumor immune microenvironment, which plays a crucial role in regulating anti-tumor immune responses. To confirm the malignant functions of NNMT in tumor cells, we conducted a series of cell-based experiments, revealing that NNMT promotes cancer cell proliferation and invasion, indicative of its oncogenic properties. The integration of computational analysis and experimental validation in our study firmly establishes NNMT as a potential therapeutic target for human cancers. Specifically, targeting NNMT holds promise for the development of innovative and effective cancer treatments. Further investigations into NNMT's role in cancer pathogenesis could potentially pave the way for groundbreaking advancements in cancer treatment.

Aiolos (IKZF3), a zinc finger transcription factor, has been identified in various solid tumors. While most research on Aiolos focuses on its role in the hematopoietic system, its expression patterns, mechanisms of action, and biological impacts in lung cancer remain relatively unexplored. This study investigates Aiolos’ role in the proliferation, migration, and invasion of lung cancer cells. Our findings indicate that Aiolos overexpression enhances these cellular processes, suggesting its potential contribution to the advancement of the disease. However, the precise mechanisms underlying these effects require further investigation. Additionally, we identified OTUB1 as a potential Aiolos-interacting protein. OTUB1, a deubiquitinating enzyme, removes ubiquitin chains from target proteins, thereby affecting their stability, function, or localization. Our results suggest that OTUB1 specially bound to Aiolos and reduces its ubiquitination, which may influence Aiolos-related biological functions, including cell migration and invasion. This study highlights the pivotal roles of Aiolos and OTUB1 in lung cancer progression, potentially offering new therapeutic targets.

Abstract Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein‐Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV‐ (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC‐associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene‐edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV‐coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV‐ and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.

BackgroundMitochondrial unfolded protein response (mtUPR) plays an essential role in the response of mitochondria to stress-induced damage. Activating of transcription factor 5 (ATF5) can help to sustain mitochondrial function and regulate organelle recovery under mitochondrial stress. Vitrification is a stressor that disrupts mitochondrial activity and cell homeostasis. However, little is known about the function of ATF5 in response to the extreme biophysical and chemical stresses during oocyte vitrification.MethodsThe expression of ATF5 and mtUPR biomarkers were measured in fresh and vitrified oocytes. Subsequently, oocytes with ATF5 deficiency were constructed by siRNA microinjection, and the function of ATF5 in mitochondrial function and oocyte development were analyzed in vitrified oocytes. Furthermore, transcriptome analysis was performed to uncover the molecular network regulated by ATF5 in response to oocyte vitrification.ResultsIn the present study, the mitochondrial membrane potential and ATP levels were decreased in ATF5 knockdown oocytes, in line with the phenotypes observed in vitrified oocytes. In addition, ATF5 knockdown resulted in decreased mitochondrial temperature, reduced unfolded protein levels, abnormal mitochondrial dynamics (fusion and fission), and increased autophagy. Subsequent experiments indicated that mtUPR was suppressed in oocytes with ATF5 knockdown. Interestingly, ATF5 was aberrantly upregulated in oocytes exposed to vitrification stress. Reduced ATF5 expression to a homeostatic level in vitrified oocytes led to accumulated unfolded protein levels and increased mitochondrial membrane potential. Moreover, increased mitochondrial dynamics and an increased germinal vesicle breakdown (GVBD) rate were detected after in vitro maturation. Transcriptome analysis revealed that ATF5 is involved in the vitrification stress response, and ATF5 regulated the in vitro maturation potential in vitrified oocytes through the cAMP-PKA and PI3K/AKT pathways.DiscussionOur findings indicate that mtUPR was initiated in response to vitrification stimuli, and downregulated ATF5 level to a homeostatic state contributes to improved mitochondrial function in oocytes exposed to vitrification stress. Our results highlight the crucial role of ATF5 in the regulation of mitochondrial function in vitrified oocytes through mediating mtUPR.

Abstract Gastrointestinal tumors, the second leading cause of human mortality, are characterized by their association with inflammation. Currently, progress in the early diagnosis and effective treatment of gastrointestinal tumors is limited. Recent whole‐genome analyses have underscored their profound heterogeneity and extensive genetic and epigenetic reprogramming. Epigenetic reprogramming pertains to dynamic and hereditable alterations in epigenetic patterns, devoid of concurrent modifications in the underlying DNA sequence. Common epigenetic modifications encompass DNA methylation, histone modifications, noncoding RNA, RNA modifications, and chromatin remodeling. These modifications possess the potential to invoke or suppress a multitude of genes associated with cancer, thereby governing the establishment of chromatin configurations characterized by diverse levels of accessibility. This intricate interplay assumes a pivotal and indispensable role in governing the commencement and advancement of gastrointestinal cancer. This article focuses on the impact of epigenetic reprogramming in the initiation and progression of gastric cancer, esophageal cancer, and colorectal cancer, as well as other uncommon gastrointestinal tumors. We elucidate the epigenetic landscape of gastrointestinal tumors, encompassing DNA methylation, histone modifications, chromatin remodeling, and their interrelationships. Besides, this review summarizes the potential diagnostic, therapeutic, and prognostic targets in epigenetic reprogramming, with the aim of assisting clinical treatment strategies.

IntroductionPostpartum endometritis is a prevalent reproductive disorder in bovines, leading to a prolonged open period, infertility, and other complications. While Lactobacillus strains can mitigate these conditions by reducing uterine inflammation, their effectiveness is limited due to a lack of direct anti microbial action and extended treatment duration. This study aimed to construct a recombinant Lactobacillus johnsonii strain expressing bovine Granulocyte-macrophage colony-stimulating factor (GM-CSF) to evaluate its potential in reducing postpartum uterine inflammation.MethodsThe recombinant Lactobacillus johnsonii strain was engineered to express bovine GM-CSF and administered to pregnant mice via vaginal perfusion. Postpartum endometritis was induced using E. coli infection, and the protective effects of the engineered strain were assessed. Inflammatory markers (IL-6, IL-1β, TNF-α), myeloperoxidase (MPO) activity, and nitric oxide (NO) concentration were measured. Histological examination was performed to evaluate uterine morphology and pathological damage.ResultsThe recombinant L. johnsonii strain expressing GM-CSF significantly reduced inflammation levels induced by E. coli infection in the uterus. This reduction was evidenced by decreased expression of IL-6, IL-1β, TNF-α, as well as reduced MPO activity and NO concentration. Histological examination revealed improved uterine morphology and reduced pathological damage in mice treated with the recombinant GM-CSF strain. Crucially, the recombinant strain also exerts beneficial effects on bovine endometritis by reducing levels of inflammatory cytokines, suggesting a beneficial effect on clinical bovine endometritis.ConclusionThe recombinant Lactobacillus johnsonii expressing GM-CSF demonstrated protective effects against postpartum endometritis in bovines by reducing inflammatory cytokines. The findings indicate the potential clinical application of this engineered strain in preventing postpartum uterine inflammation, offering a novel and effective protective option for related disorders and improving bovine reproductive efficiency.

Microbiota in the reproductive tract of cattle play a vital role in maintaining normal reproduction. However, the information on microbiota in different parts of reproductive tracts with different genetic background is few. The aim of the present study was to describe and compare the microbiota in vagina, cervix and uterus of Yanbian cattle and Yanhuang cattle. The results showed that microbial diversity increases from the vagina to the uterus. The top three bacterial phyla in bovine reproductive tract were Proteobacteria, Firmicutes and Bacteroidetes, accounting for more than 85%. From the vagina to the uterus, the relative abundance of Proteobacteria gradually decreased, while that of Firmicutes gradually increased. Phylum-level Firmicutes and genus-level UCG_010 were significantly enriched in the uterus of Yanbian cattle and Yanhuang cattle. Comparing the same parts of the two breeds, it was found that there was no significant difference in alpha diversity, but significant differences in beta diversity. In addition, microbiota with significant differences in the relative abundance of the reproductive tract were found. These findings lay a foundation for a comprehensive understanding of the structure of the genital tract microbiota of cows and its regulatory mechanisms.

Abstract Mg‐ion batteries (MIBs) are promising next‐generation secondary batteries, but suffer from sluggish Mg2+ migration kinetics and structural collapse of the cathode materials. Here, an H2O‐Mg2+ waltz‐like shuttle mechanism in the lamellar cathode, which is realized by the coordination, adaptive rotation and flipping, and co‐migration of lattice H2O molecules with inserted Mg2+, leading to the fast Mg2+ migration kinetics, is reported; after Mg2+ extraction, the lattice H2O molecules rearrange to stabilize the lamellar structure, eliminating structural collapse of the cathode. Consequently, the demo cathode of Mg0.75V10O24·nH2O (MVOH) exhibits a high capacity of 350 mAh g−1 at a current density of 50 mA g−1 and maintains a capacity of 70 mAh g−1 at 4 A g−1. The full aqueous MIB based on MVOH delivers an ultralong lifespan of 5000 cycles The reported waltz‐like shuttle mechanism of lattice H2O provides a novel strategy to develop high‐performance cathodes for MIBs as well as other multivalent‐ion batteries.

Background and objective Lung cancer is a leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) is the most common pathological subtype, with adenocarcinoma being the predominant type. FAT atypical cadherin 1 (FAT1) is a receptor-like protein with a high frequency of mutations in lung adenocarcinoma. The protein encoded by FAT1 plays a crucial role in processes such as cell adhesion, proliferation, and differentiation. This study aims to investigate the expression of FAT1 in lung adenocarcinoma and its relationship with immune infiltration. Methods Gene expression levels and relevant clinical information of 513 lung adenocarcinoma samples and 397 adjacent lung samples were obtained through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data. The mRNA expression levels of the FAT1 gene in lung adenocarcinoma tissues were analyzed, along with its association with the prognosis of lung adenocarcinoma patients. Pathway enrichment analysis was conducted to explore the signaling pathways regulated by the FAT1 gene. Immunoblotting was used to detect the differential expression of FAT1 in lung epithelial cells and various lung cancer cell lines, while immunohistochemistry was employed to assess FAT1 expression in lung cancer and adjacent tissues. Results FAT1 gene mutations were identified in 14% of lung adenocarcinoma patients. TCGA database data revealed significantly higher FAT1 mRNA expression in lung adenocarcinoma tissues compared to adjacent lung tissues. Kaplan-Meier analysis indicated lower survival rates in lung adenocarcinoma patients with higher FAT gene expression. Pathway enrichment analysis suggested the involvement of FAT1 in tumor development pathways, and its expression was closely associated with immune cell infiltration. Immunohistochemical validation demonstrated significantly higher expression of FAT1 in cancer tissues compared to adjacent lung tissues. Conclusion FAT1 mRNA is highly expressed in lung adenocarcinoma tissues, and elevated FAT1 mRNA expression is associated with poor prognosis in lung adenocarcinoma patients. FAT1 may serve as a potential biomarker for lung cancer.

Chronic tinnitus is highly prevalent but lacks precise diagnostic or effective therapeutic standards. Its onset and treatment mechanisms remain unclear, and there is a shortage of objective assessment methods. We aim to identify abnormal neural activity and reorganization in tinnitus patients and reveal potential neurophysiological markers for objectively evaluating tinnitus. By way of analyzing EEG microstates, comparing metrics under three resting states (OE, CE, and OECEm) between tinnitus sufferers and controls, and correlating them with tinnitus symptoms. This study reflected specific changes in the EEG microstates of tinnitus patients across multiple resting states, as well as inconsistent correlations with tinnitus symptoms. Microstate parameters were significantly different when patients were in OE and CE states. Specifically, the occurrence of Microstate A and the transition probabilities (TP) from other Microstates to A increased significantly, particularly in the CE state (32-37%, ${p}\le 0.05$ ); and both correlated positively with the tinnitus intensity. Nevertheless, under the OECEm state, increases were mainly observed in the duration, coverage, and occurrence of Microstate B (15-47%, ${p} < 0.05$ ), which negatively correlated with intensity ( $\text{R} < $ -0.513, ${p} < 0.05$ ). Additionally, TPx between Microstates C and D were significantly reduced and positively correlated with HDAS levels ( $\text{R}>$ 0.548, ${p} < 0.05$ ). Furthermore, parameters of Microstate D also correlated with THI grades ( $\text{R} < $ -0.576, ${p} < 0.05$ ). The findings of this study could offer compelling evidence for central neural reorganization associated with chronic tinnitus. EEG microstate parameters that correlate with tinnitus symptoms could serve as neurophysiological markers, contributing to future research on the objective assessment of tinnitus.

Background and objective Transcription factor (TF) can bind specific sequences that either promotes or represses the transcription of target genes, and exerts important effects on tumorigenesis, migration, invasion. Staphylococcal nuclease-containing structural domain 1 (SND1), which is a transcriptional co-activator, is considered as a promising target for tumor therapy. However, its role in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore the role of SND1 in LUAD. Methods Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) database was obtained to explore the association between SND1 and the prognosis, as well as the immune cell infiltration, and subcellular localization in LUAD tissues. Furthermore, the functional role of SND1 in LUAD was verified in vitro. EdU assay, CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot were performed. Results SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients. In addition, SND1 was predominantly present in the cytoplasm of LUAD cells. Enrichment analysis showed that SND1 was closely associated with the cell cycle, as well as DNA replication, and chromosome segregation. Immune infiltration analysis showed that SND1 was closely associated with various immune cell populations, including T cells, B cells, cytotoxic cells and dendritic cells. In vitro studies demonstrated that silencing of SND1 inhibited cell proliferation, invasion and migration of LUAD cells. Besides, cell cycle was blocked at G1 phase by down-regulating SND1. Conclusion SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

The recently emerged Al–Mn–Mg–Sc–Zr alloys were regarded as high-strength Al alloys suitable for high-temperature applications. However, the influence of laser powder bed fusion (LPBF) fabricated anisotropic microstructure on tensile creep performance has not been explored. In this work, we reported an anisotropic tensile creep behavior, which is superior in the vertical specimens than the horizontal counterparts. The tensile creep anisotropy was attributed to the bi-modal microstructure of columnar grains within melt pool and equiaxed grains at melt pool boundary, the “fish-scale” melt pool morphology and the resulted tortuous crack path in the vertical orientation.

Abstract Nitrogen has a critical influence on the yield and quality of proso millet. However, the exact impact of nitrogen on the cooking quality of proso millet is not clear. In this study, the cooking quality and starch properties of two proso millet varieties (waxy‐Shaanxi millet [wSM] variety and non‐waxy‐Shaanxi millet [nSM] variety) were compared and analyzed under nitrogen fertilizer treatment (N150, 150 kg/hm2) and a control group without nitrogen application (N0, 0 kg/hm2). Compared with the N0 group, the N150 treatment significantly increased protein content, amylose levels, and total yield. Employing rapid visco analyser and differential scanning calorimetry analyses, we observed that under the N150 treatment, the peak viscosity and breakdown viscosity of proso millet powder were diminished, while the setback viscosity and enthalpy values (ΔH) increased. In addition, nitrogen treatment increased the solids content in the obtained rice soup and significantly hardened the texture of the rice. At the same time, we noticed that the absorption capacity of starch in water and oil was enhanced. These results showed that nitrogen fertilizer had significant effects on the cooking quality and starch properties of proso millet.

Objective This study aimed to examine the prevalence of dyslexia, mental health problems, and character strengths among primary school students in northwest China.Method Primary school students (N = 2,322) were assessed for dyslexia, strengths and difficulties, self-esteem, bullying, depression, anxiety, and character strengths. The Student’s t-test and χ2 test were used to compare continuous and categorical variables between students with and without dyslexia.Results The estimated prevalence of dyslexia ranged from 4.9% to 6.9% and was highly prevalent among boys. Students with dyslexia reported statistically higher mean scores for emotional symptoms, conduct behaviours, internalizing and externalising problems, as well as total difficulties. Conversely, they exhibited lower levels of prosocial behaviour, expressed lower self-esteem, and reported higher instances of being bullied. Additionally, the prevalences of depression and anxiety symptoms were 36.5% and 26.3%, respectively, among dyslexic students. Signature strengths among students with dyslexia included appreciation of beauty and excellence, love, hope, forgiveness, and judgement.Conclusions These findings underscore dyslexia’s impact on mental health and academic performance in China. Implementing character strength-focused interventions could enhance well-being and academic outcomes among dyslexic primary school students.

Throughout history, the influenza A virus has caused numerous devastating global pandemics. Macrophages, as pivotal innate immune cells, exhibit a wide range of immune functions characterized by distinct polarization states, reflecting their intricate heterogeneity. In this study, we employed the time-resolved single-cell sequencing technique coupled with metabolic RNA labelling to elucidate the dynamic transcriptional changes in distinct polarized states of bone marrow-derived macrophages (BMDMs) upon infection with the influenza A virus. Our approach not only captures the temporal dimension of transcriptional activity, which is lacking in conventional scRNA-seq methods, but also reveals that M2-polarized Arg1_macrophage cluster is the sole state supporting successful replication of influenza A virus. Furthermore, we identified distinct antigen presentation capabilities to CD4+ T and CD8+ T cells across diverse polarized states of macrophages. Notably, the M1 phenotype, exhibited by (BMDMs) and murine alveolar macrophages (AMs), demonstrated superior conventional and cross-presentation abilities for exogenous antigens, with a particular emphasis on cross-presentation capacity. Additionally, as CD8+ T cell differentiation progressed, M1 polarization exhibited an enhanced capacity for cross-presentation. All three phenotypes of BMDMs, including M1, demonstrated robust presentation to CD4+ regulatory T cells, while displaying limited ability to present to naive CD4+ T cells. These findings offer novel insights into the immunological regulatory mechanisms governing distinct polarized states of macrophages, particularly their roles in restricting the replication of influenza A virus and modulating antigen-specific T cell responses through innate immunity.

Enzymatic soybean phospholipids are single-chain fatty acyl phospholipid derivatives produced by the natural degradation of phospholipids by phospholipase enzymes by breaking the ester bond from the 1-position or 2-position, resulting in a mixture of phospholipids enriched in lysophospholipids. An 8-week feeding experiment was conducted to study the effects of enzymatic soybean phospholipid replacing soybean oil on growth performance, glycolipid metabolism and intestinal microflora of largemouth bass (Micropterus salmoides). The experiment was divided into 3 treatment groups with 3 replicates per treatment component. Each net contained 30 fish (Initial weight = 9.14 ± 0.04 g). A diet containing fish oil and soybean oil was used as the control (P0) and ESP replaced 30 % (P30) and 50 % (P50) of soybean oil in the other dietary groups. The results showed that the weight gain rate and protein efficiency ratio; amylase, lipase and trypsin in the intestine; and total antioxidant capacity, superoxide dismutase, hexokinase, glucokinase, 6-phosphate dehydrogenase and lipoprotein lipase activities in the liver were higher in the P50 group than in the P0 and P30 groups, while feeding rate, viscerosomatic index; total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol in the serum and malondialdehyde in the liver were lower than in the P0 group significantly (P < 0.05). The expressions of hormone-sensitive lipase, apolipoprotein A1 and fatty acid synthase in P50 group were higher than those in P0 and P30 groups, and the expressions of lipoprotein lipase, carnitine palmitoyl transferase, adipose triglyceride lipase and apolipoprotein B-100 in P50 group were higher than those in P0 group significantly (P < 0.05). Villi width, villi height and lamina propria thickness in P50 group were higher than those in P0 and P30 group, and lamina propria thickness in P30 group was higher than that in P0 group significantly (P < 0.05). The results of the intestinal flora showed that at the level of phylum, the relative abundance of Proteobacteria increased and that of Tenericutes and Firmicutes decreased in the P50 group compared to the P0 group. At the genus level, the relative abundance of Mycoplasma and Aeromonas decreased, and that of Plesiomonas increased in the P50 group compared to the P0 group. In conclusion, replacement of 50 % soybean oil with ESP significantly promoted the growth of largemouth bass, improved the antioxidant capacity of the organism, promoted carbohydrate utilisation and lipid metabolism, as well as enhanced the stability of the intestinal microflora.

Introduction: Pycnogenol (PYC), a standardized extract from French maritime pine, has traditionally been used to treat inflammation. However, its primary active components and their mechanisms of action have not yet been determined.Methods: This study employed UPLC-MS/MS (Ultra-high performance liquid chromatography-tandem mass spectrometry) and network pharmacology to identify the potential active components of PYC and elucidate their anti-inflammatory mechanisms by cell experiments.Results: 768 PYC compounds were identified and 19 anti-inflammatory compounds were screened with 85 target proteins directly involved in the inflammation. PPI (protein-protein interaction) analysis identified IL6, TNF, MMP9, IL1B, AKT1, IFNG, CXCL8, NFKB1, CCL2, IL10, and PTGS2 as core targets. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis suggested that the compound in PYC might exert anti-inflammatory effects through the IL17 and TNF signal pathways. Cell experiments determined that PYC treatment can reduce the expression of IL6 and IL1β to relieve inflammation in LPS (lipopolysaccharide)-induced BV2 cells.Conclusion: PYC could affect inflammation via multi-components, -targets, and -mechanisms.

ObjectiveTo evaluate the association between bedtime and infertility and to identify the optimal bedtime for women of reproductive age.MethodsWe conducted a cross-sectional study using data from 3,903 female participants in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2020. The effect of bedtime on female infertility was assessed using the binary logistic regression in different models, including crude model and adjusted models. To identify the non-linear correlation between bedtime and infertility, generalized additive models (GAM) were utilized. Subgroup analyses were conducted by age, body mass index (BMI), waist circumference, physical activity total time, marital status, smoking status, drinking status and sleep duration.ResultsAfter adjusting for potential confounders (age, race, sleep duration, waist circumference, marital status, education, BMI, smoking status, drinking status and physical activity total time), a non-linear relationship was observed between bedtime and infertility, with the inflection point at 22:45. To the left side of the inflection point, no significant association was detected. However, to the right of it, bedtime was positively related to the infertility (OR: 1.22; 95% CI: 1.06 to 1.39; P = 0.0049). Subgroup analyses showed that late sleepers with higher BMI were more prone to infertility than those with a lower BMI (BMI: 25–30 kg/m2: OR: 1.26; 95% CI: 1.06 to 1.51; P = 0.0136; BMI ≥ 30 kg/m²: OR: 1.21, 95% CI: 1.09 to 1.34; P = 0.0014).ConclusionBedtime was non-linearly associated with infertility, which may provide guidance for sleep behavior in women of childbearing age.

FAT1, a substantial transmembrane protein, plays a pivotal role in cellular adhesion and cell signaling. Numerous studies have documented frequent alterations in FAT1 across various cancer types, with its aberrant expression being linked to unfavorable survival rates and tumor progression. In the present investigation, we employed bioinformatic analyses, as well as in vitro and in vivo experiments to elucidate the functional significance of FAT1 in pan-cancer, with a primary focus on lung cancer. Our findings unveiled FAT1 overexpression in diverse cancer types, including lung cancer, concomitant with its association with an unfavorable prognosis. Furthermore, FAT1 is intricately involved in immune-related pathways and demonstrates a strong correlation with the expression of immune checkpoint genes. The suppression of FAT1 in lung cancer cells results in reduced cell proliferation, migration, and invasion. These collective findings suggest that FAT1 has potential utility both as a biomarker and as a therapeutic target for lung cancer.

The suppressor of cytokine signaling 3 (SOCS3) is a key signaling molecule that regulates milk synthesis in dairy livestock. However, the molecular mechanism by which SOCS3 regulates lipid synthesis in goat milk remains unclear. This study aimed to screen for key downstream genes associated with lipid synthesis regulated by SOCS3 in goat mammary epithelial cells (GMECs) using RNA sequencing (RNA-seq). Goat SOCS3 overexpression vector (PC-SOCS3) and negative control (PCDNA3.1) were transfected into GMECs. Total RNA from cells after SOCS3 overexpression was used for RNA-seq, followed by differentially expressed gene (DEG) analysis, functional enrichment analysis, and network prediction. SOCS3 overexpression significantly inhibited the synthesis of triacylglycerol, total cholesterol, non-esterified fatty acids, and accumulated lipid droplets. In total, 430 DEGs were identified, including 226 downregulated and 204 upregulated genes, following SOCS3 overexpression. Functional annotation revealed that the DEGs were mainly associated with lipid metabolism, cell proliferation, and apoptosis. We found that the lipid synthesis-related genes, STAT2 and FOXO6, were downregulated. In addition, the proliferation-related genes BCL2, MMP11, and MMP13 were upregulated, and the apoptosis-related gene CD40 was downregulated. In conclusion, six DEGs were identified as key regulators of milk lipid synthesis following SOCS3 overexpression in GMECs. Our results provide new candidate genes and insights into the molecular mechanisms involved in milk lipid synthesis regulated by SOCS3 in goats.

Bone is a highly dynamic organ that changes with the daily circadian rhythm. During the day, bone resorption is suppressed due to eating, while it increases at night. This circadian rhythm of the skeleton is regulated by gut hormones. Until now, gut hormones that have been found to affect skeletal homeostasis include glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), which exerts its effects by binding to its cognate receptors (GLP-1R, GLP-2R, GIPR, and Y1R). Several studies have shown that GLP-1, GLP-2, and GIP all inhibit bone resorption, while GIP also promotes bone formation. Notably, PYY has a strong bone resorption-promoting effect. In addition, gut microbiota (GM) plays an important role in maintaining bone homeostasis. This review outlines the roles of GLP-1, GLP-2, GIP, and PYY in bone metabolism and discusses the roles of gut hormones and the GM in regulating bone homeostasis and their potential mechanisms.

BackgroundIntegrin subunit alpha L (ITGAL) encodes an integrin component of LFA-1 and is a membrane receptor molecule widely expressed on leukocytes. It plays a key role in the interaction between white blood cells and other cells. There was a significant correlation between the expression of ITGAL and the tumor microenvironment in a number of cancers. However, experimental studies targeting ITGAL and immune cell infiltration in non-small-cell lung cancer (NSCLC) and the response to immune checkpoint inhibitor therapy are lacking.MethodsData were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases to explore the relationship between ITGAL expression and prognosis, as well as the immune cell infiltration in patients with NSCLC. In addition, immunohistochemical staining for ITGAL and multiplex immunofluorescence (mIF) staining for ITGAL, CD20, CD68, CD4, and CD8 from tissue microarrays containing 118 tumor tissues and paired paracancerous tissues from patients with NSCLC were performed. The correlation between ITGAL expression and clinical factors, as well as the immunophenotypes of tumor-infiltrating immune cells, were also analyzed.ResultsIn NSCLC tumor tissues, ITGAL was downregulated compared with matched paracancerous tissues, and low ITGAL expression was associated with a poor prognosis of NSCLC patients. Subsequently, immunohistochemistry results for tissue microarray showed that ITGAL expression was mainly elevated in tumor stroma and areas with highly infiltrated immune cells. ITGAL expression was higher in paracancerous tissues than tumor tissues. Furthermore, mIF results indicated that the patients with ITGAL-high expression tend had significantly higher CD8+ T cells, CD68+ macrophages, CD4+ T cells, and CD20+ B cells infiltration in their tumor tissues. Immunophenotypes were classified into three categories, that is deserted, excluded, and inflamed types, according to each kind of immune cell distribution in or around the cancer cell nest. MIF results showed that ITGAL expression level was correlated with the immunophenotypes. Furthermore, ITGAL expression was associated with the prognosis of NSCLC in patients with immune checkpoint inhibitor therapy and the patients with high ITGAL expression tends have better outcomes.ConclusionsITGAL may be used as a biomarker for assessing the immune microenvironment in patients with NSCLC.

Abstract Investor sentiment contagion has a profound influence on economic and social development. This paper explores the diverse influences of various investor sentiments in modern society on the economy and society. It also investigates the interference of various uncertain factors on investor sentiments in the modern economy and society. On this basis, the dual-system stochastic SPA2G2R model was constructed, incorporating positive and negative sentiments, as well as a supervision and isolation mechanism. The global existence of positive solutions was established, and sufficient conditions for the disappearance and steady distribution of investor sentiment were calculated. An optimal control strategy for the stochastic model was put forward, with numerical simulation supporting the theoretical analysis results. A comparison with parameter changes in the deterministic model was also conducted. The research reveals a competitive relationship between different investor sentiments. Enhancing societal guidance mechanisms promotes positive investor sentiment contagion. Timely control by the supervisory department effectively curbs the spread of investor sentiment. Additionally, white noise promotes investor sentiment contagion, suggesting effective regulation through control of noise intensity and disturbance parameters.

Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKI) acquired resistance was an inevitably events in NSCLC treatment. Aims Intending to overcome the acquired resistance of EGFR‐TKI. Materials & Methods A clinical trial was, we enrolled 12 patients who were slowly progressing on first‐generation EGFR‐TKI, and added apatinib when the patients got slow progression. Results Seven patients were included in the efficacy analysis. The median PFS2 of apatinib combined with EGFR‐TKI was 8.2 months (95% CI, 7.3 m‐NA), and the total PFS reached 20.9 months (95% CI, 17.3 m‐NA) when plus PFS1. All the adverse events were manageable. The median PFS was significantly longer for circulating tumor DNA (ctDNA)‐cleared patients (8.4 months; 95% CI, 8.2‐NA) than for those ctDNA not cleared (7.1 months; 95% CI, 6.9‐NA) (p = 0.0082). Discussion The addition of apatinib did improve the duration of first‐generation EGFR‐TKI use, and the duration was better than the first‐line use of third‐generation EGFR‐TKI. Conclusion The addition of apatinib when the patients got slow progression after initial EGFR‐TKI therapy may be a good treatment option and the side effects are controllable. It is possible to monitor treatment efficacy using ctDNA.

Abstract Background The entomogenous fungus Beauveria bassiana is used as a biological insecticide worldwide, wild B. bassiana strains with high pathogenicity in the field play an important role in controlling insect pests via not only screening of highly virulent strains but also natural infection, but the pathogenicity degeneration of wild strains severely affected aforementioned effects. Previous studies have showed that multiple factors contributed to this phenomenon. It has been extensively proved that the mycovirus infection caused hypovirulence of phytopathogenic fungi, which has been used for plant disease biocontrol. However, it remains unknown whether the mycovirus epidemics is a key factor causing hypovirulence of B. bassiana naturally in the field. Methods Wild strains of B. bassiana were collected from different geographic locations in Jilin Province, China, to clarify the epidemic and diversity of the mycoviruses. A mycovirus Beauveria bassiana chrysovirus 2 (BbCV2) we have previously identified was employed to clarify its impact on the pathogenicity of host fungi B. bassiana against the larvae of insect pest Ostrinia furnacalis. The serological analysis was conducted by preparing polyclonal antibody against a BbCV2 coat protein, to determine whether it can dissociate outside the host fungal cells and subsequently infect new hosts. Transcriptome analysis was used to reveal the interactions between viruses and hosts. Results We surprisingly found that the mycovirus BbCV2 was prevalent in the field as a core virus in wild B. bassiana strains, without obvious genetic differentiation, this virus possessed efficient and stable horizontal and vertical transmission capabilities. The serological results showed that the virus could not only replicate within but also dissociate outside the host cells, and the purified virions could infect B. bassiana by co-incubation. The virus infection causes B. bassiana hypovirulence. Transcriptome analysis revealed decreased expression of genes related to insect epidermis penetration, hypha growth and toxin metabolism in B. bassiana caused by mycovirus infection. Conclusion Beauveria bassiana infected by hypovirulence-associated mycovirus can spread the virus to new host strains after infecting insects, and cause the virus epidemics in the field. The findings confirmed that mycovirus infection may be an important factor affecting the pathogenicity degradation of B. bassiana in the field.

Abstract Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3 −) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional l-arginine–NO synthase (l-NOS) pathway, whereas endogenous NO production by l-arginine is inhibited under hypoxia–ischemia or disease conditions. In contrast, exogenous NO3 −/NO2 −/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3 −/NO2 −/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3 −/NO2 −/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.

Unmanned sailboats can convert wind energy with sails to provide power for navigation, which can independently plan routes and collect data without human intervention. They have received increasing attention in recent years due to their low power consumption and strong self-sustainability. Due to the greater difficulty of manipulation, the unmanned sailboats have a weaker maneuverability than the propeller-driven vessels in the complex and variable marine environment. Typically, the turning motion is evaluated to characterize the maneuverability of a vessel, which has rarely been investigated in the existing research on unmanned sailboats. Therefore, this study builds a motion simulation platform for unmanned sailboats based on the 3 m class Petrel Sail to investigate the turning characteristics. The index of the approximate turning circle is introduced based on the turning motion trajectory, which is used to obtain the effect of rudder angle, wind angle, wind speed, and current speed on the turning performance of the sailboat in ideal hydrostatic conditions and under flow disturbance, respectively. Finally, a harbor pool test is conducted with an unmanned sailboat to verify the analysis results, and the errors in maximum transverse distance and maximum advance distance are in the reasonable range, proving the correctness of the theoretical results. The current study also provides theoretical guidance for subsequent research on sailboat manipulation and maneuverability.

Bos taurus is known for its tolerance of coarse grains, adaptability, high temperature, humidity, and disease resistance. Primarily, cattle are raised for their meat and milk, and pinpointing genes associated with traits relevant to meat production can enhance their overall productivity. The aim of this study was to identify the genome, analyze the evolution, and explore the function of the Pax gene family in B. taurus to provide a new molecular target for breeding in meat-quality-trait cattle. In this study, 44 Pax genes were identified from the genome database of five species using bioinformatics technology, indicating that the genetic relationships of bovids were similar. The Pax3 and Pax7 protein sequences of the five animals were highly consistent. In general, the Pax gene of the buffalo corresponds to the domestic cattle. In summary, there are differences in affinity between the Pax family genes of buffalo and domestic cattle in the Pax1/9, Pax2/5/8, Pax3/7, and Pax4/6 subfamilies. We believe that Pax1/9 has an effect on the growth traits of buffalo and domestic cattle. The Pax3/7 gene is conserved in the evolution of buffalo and domestic animals and may be a key gene regulating the growth of B. taurus. The Pax2/5/8 subfamily affects coat color, reproductive performance, and milk production performance in cattle. The Pax4/6 subfamily had an effect on the milk fat percentage of B. taurus. The results provide a theoretical basis for understanding the evolutionary, structural, and functional characteristics of the Pax family members of B. taurus and for molecular genetics and the breeding of meat-production B. taurus species.

Controlled generation of cytotoxic reactive oxygen species (ROS) is essential in cancer therapy. Ultrasound (US)-triggered sonodynamic therapy (SDT) has shown considerable ability to trigger in situ ROS generation. Unfortunately, US therapy alone is insufficient to trigger an efficient anticancer response, owing to the induction of multiple immunosuppressive factors. It was identified that 7-ethyl-10-hydroxycamptothecin (SN38) could notably inhibit DNA topoisomerase I, induce DNA damage and boost robust anticancer immunity. However, limited by the low metabolic stability, poor bioavailability, and dose-limiting toxicity, the direct usage of SN38 is inadequate in immune motivation, which limits its clinical application. Hence, new strategies are needed to improve drug delivery efficiency to enhance DNA topoisomerase I inhibition and DNA damage and elicit a vigorous anticancer cancer immunity response. Considering US irradiation can efficiently generate large amounts of ROS under low-intensity irradiation, in this study, we aimed to design a polymeric, ROS-responsive SN38 nanoformulation for in vivo drug delivery. Upon the in-situ generation of ROS by US therapy, controlled on-demand release of SN38 occurred in tumor sites, which enhanced DNA damage, induced DC cell maturation, and boosted anticancer immunity. Our results demonstrated that a new strategy of involving the combination of a SN38 nanoformulation and US therapy could be used for cancer immunotherapy.

Diode-pumped rare gas lasers (DPRGLs) have the potential for high optical conversion efficiency and excellent beam quality, positioning them as promising candidates for directed energy lasers. This study proposes a semi-analytical model for a flowing gas diode-pumped rare gas laser considering the influence of temperature elevation resulting from increased pump power on the output. Furthermore, we explore the relationship between laser output power density and gas temperature with respect to gas flow velocity. The results of numerical simulation agree well with those of Rawlins et al.’s experiment. The model addresses the existing gap in DPRGL dynamic models by incorporating temperature considerations, emphasizing the crucial role of a gas flow device in achieving high-energy laser. With the best set of parameters, the output power of DPRGL reaches 100 kW/cm2, at pumping power density of 300 kW/cm2 and gas flow velocity of 140 m/s. Parameter optimization is helpful for design of a relatively high-power DPRGL system.

Abstract Colorectal cancer (CRC) is generally characterized by a high prevalence of Fusobacterium nucleatum (F. nucleatum), a spindle‐shaped, Gram‐negative anaerobe pathogen derived from the oral cavity. This tumor‐resident microorganism has been closely correlated with the occurrence, progression, chemoresistance and immunosuppressive microenvironment of CRC. Furthermore, F. nucleatum can specifically colonize CRC tissues through adhesion on its surface, forming biofilms that are highly resistant to commonly used antibiotics. Accordingly, it is crucial to develop efficacious non‐antibiotic approaches to eradicate F. nucleatum and its biofilms for CRC treatment. In recent years, various antimicrobial strategies, such as natural extracts, inorganic chemicals, organic chemicals, polymers, inorganic‐organic hybrid materials, bacteriophages, probiotics, and vaccines, have been proposed to combat F. nucleatum and F. nucleatum biofilms. This review summarizes the latest advancements in anti‐F. nucleatum research, elucidates the antimicrobial mechanisms employed by these systems, and discusses the benefits and drawbacks of each antimicrobial technology. Additionally, this review also provides an outlook on the antimicrobial specificity, potential clinical implications, challenges, and future improvements of these antimicrobial strategies in the treatment of CRC.

Abstract Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte‐leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.

Allocation strategy is a way to find problems inside the network, and it is also a way to put problems at the edge of the network. In the central router scheme, each router decides when to transmit data packets and which data packets to reject, and at the same time notifies the host generating network traffic to send the packet number. In the central hosting scheme, the final host monitors the network status and adjusts its behavior accordingly. Ice and snow sports has gradually become a way of entertainment for people, improving their knowledge of physical exercise. Various forms of physical activities have been taken, such as shooting, running, jumping, walking, and dancing, and these exercises are usually general forms of physical exercise. This article is about the dissemination of concepts, methods and techniques of advanced training, scientific research and winter sports training, as well as the study of methods and techniques for the sustainable development of national ice and snow sports, winter sports training, and ice and snow economy.

Information dissemination has a significant impact on social development. This paper considers that there are many stochastic factors in the social system, which will result in the phenomena of information cross-dissemination and variation. The dual-system stochastic susceptible-infectious-mutant-recovered model of information cross-dissemination and variation is derived from this problem. Afterward, the existence of the global positive solution is demonstrated, sufficient conditions for the disappearance of information and its stationary distribution are calculated, and the optimal control strategy for the stochastic model is proposed. The numerical simulation supports the results of the theoretical analysis and is compared to the parameter variation of the deterministic model. The results demonstrate that cross-dissemination of information can result in information variation and diffusion. Meanwhile, white noise has a positive effect on information dissemination, which can be improved by adjusting the perturbation parameters.

Abstract Yak has been subject to natural selection, human domestication and interspecific introgression during its evolution. However, genetic variants favored by each of these processes have not been distinguished previously. We constructed a graph-genome for 47 genomes of 7 cross-fertile bovine species. This allowed detection of 57,432 high-resolution structural variants (SVs) within and across the species, which were genotyped in 386 individuals. We distinguished the evolutionary origins of diverse SVs in domestic yaks by phylogenetic analyses. We further identified 334 genes overlapping with SVs in domestic yaks that bore potential signals of selection from wild yaks, plus an additional 686 genes introgressed from cattle. Nearly 90% of the domestic yaks were introgressed by cattle. Introgression of an SV spanning the KIT gene triggered the breeding of white domestic yaks. We validated a significant association of the selected stratified SVs with gene expression, which contributes to phenotypic variations. Our results highlight that SVs of different origins contribute to the phenotypic diversity of domestic yaks.

Several reports have revealed the vital role that probiotics play in fish growth and health. However, few works are available for host gut-derived probiotics on the growth, immunity, and gut microbiota of fish, especially in hybrid grouper (♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatus) due to their isolation difficulty and functional verification. This study aimed at assessing 3 host gut-derived Bacillus species' effects on the growth, immune and antioxidant-biochemical responses, haematological parameters, intestinal morphology, immune-related gene expression, gut microbiota, and disease resistance against Vibrio harveyi in hybrid grouper. A total of 480 hybrid grouper (initial weight = 9.03 ± 0.02 g) were randomly allotted into 4 groups, namely, the group fed a basal diet without probiotic inclusion (control, B0), the group fed the basal diet with Bacillus velezensis GPSAK4 (BV), the group fed the basal diet with Bacillus subtilis GPSAK9 (BS), and the group fed the basal diet with Bacillus tequilensis GPSAK2 (BT) strains at 1.0 × 109 CFU/g. After a 6-week feeding trial, the results revealed significant improvements (P

Abstract Femtosecond vortex beams are of great scientific and practical interest because of their unique phase properties in both the longitudinal and transverse modes, enabling multi-dimensional quantum control of light fields. Until now, generating femtosecond vortex beams for applications that simultaneously require ultrashort pulse duration, high power, high vortex order, and a low cost and compact laser source has been very challenging due to the limitations of available generation methods. Here, we present a compact apparatus that generates powerful high-order femtosecond vortex pulses via astigmatic mode conversion from a mode-locked Hermite-Gaussian Yb:KGW laser oscillator in a hybrid scheme using both the translation-based off-axis pumping and the angle-based non-collinear pumping techniques. This hybrid scheme enables the generation of femtosecond vortices with a continuously tunable vortex order from the 1st up to the 30th order, which is the highest order obtained from any femtosecond vortex laser source based on a mode-locked oscillator. The average powers and pulse durations of all resulting vortex pulses are several hundred milliwatts and

Abstract Objectives Acquired resistance represents a bottleneck to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in lung cancer. Our study aimed to explore the efficacy of antiangiogenic‐based therapy in osimertinib‐resistant NSCLC patients and assess the efficacy of anlotinib in vitro study. Methods Our multicenter study retrospectively collected 268 osimertinib‐resistant NSCLC patients with EGFR T790M mutation and explored the efficacy of anlotinib in patients and in vitro. Results PFS was significantly longer in the antiangiogenic‐based therapy group than in the immunotherapy group (HR: 0.71, p = 0.050) and the chemotherapy group (HR: 0.28, p = 0.001). Both the ORR and DCR of the antiangiogenic‐based group were higher than the immunotherapy group and the chemotherapy group. Subgroup analysis showed a trend of more benefits from the anlotinib‐based therapy than the bevacizumab‐based therapy in terms of PFS (HR: 0.63, p = 0.087) and OS (HR: 0.52, p = 0.063). In vitro assays verified that anlotinib alone or combined with osimertinib exerted potent cytotoxicity to T790M‐mutant H1975 cell line with acquired osimertinib resistance. Conclusions Our study suggested that antiangiogenic‐based therapy might improve PFS and OS in EGFR‐mutant NSCLC patients with acquired resistance to osimertinib. Moreover, anlotinib‐based therapy could be a promising effective treatment for this group of patients.

Abstract Background The purpose of this paper was to systematically evaluate the application value of artificial intelligence in predicting mortality among COVID-19 patients. Methods The PubMed, Embase, Web of Science, CNKI, Wanfang, China Biomedical Literature, and VIP databases were systematically searched from inception to October 2022 to identify studies that evaluated the predictive effects of artificial intelligence on mortality among COVID-19 patients. The retrieved literature was screened according to the inclusion and exclusion criteria. The quality of the included studies was assessed using the QUADAS-2 tools. Statistical analysis of the included studies was performed using Review Manager 5.3, Stata 16.0, and Meta-DiSc 1.4 statistical software. This meta-analysis was registered in PROSPERO (CRD42022315158). Findings Of 2193 studies, 23 studies involving a total of 25 AI models met the inclusion criteria. Among them, 18 studies explicitly mentioned training and test sets, and 5 studies did not explicitly mention grouping. In the training set, the pooled sensitivity was 0.93 [0.87, 0.96], the pooled specificity was 0.94 [0.87, 0.97], and the area under the ROC curve was 0.98 [0.96, 0.99]. In the validation set, the pooled sensitivity was 0.84 [0.78, 0.88], the pooled specificity was 0.89 [0.85, 0.92], and the area under the ROC curve was 0.93 [1.00, 0.00]. In the subgroup analysis, the areas under the summary receiver operating characteristic (SROC) curves of the artificial intelligence models KNN, SVM, ANN, RF and XGBoost were 0.98, 0.98, 0.94, 0.92, and 0.91, respectively. The Deeks funnel plot indicated that there was no significant publication bias in this study (P > 0.05). Interpretation Artificial intelligence models have high accuracy in predicting mortality among COVID-19 patients and have high prognostic value. Among them, the KNN, SVM, ANN, RF, XGBoost, and other models have the highest levels of accuracy.

Berberine is an alkaloid used to treat diabetes. This experiment aimed to investigate the effects of berberine supplementation in high-carbohydrate diets on the growth performance, glucose metabolism, bile acid synthesis, liver transcriptome, and intestinal flora of Nile tilapia. The six dietary groups were the C group with 29% carbohydrate, the H group with 44% carbohydrate, and the HB1-HB4 groups supplemented with 25, 50, 75, and 100 mg/kg of berberine in group H. The results of the 8-week trial showed that compared to group C, the abundance of Bacteroidetes was increased in group HB2 (p < 0.05). The cholesterol-7α-hydroxylase (CYP7A1) and sterol-27-hydroxylase (CYP27A1) activities were decreased and the expression of FXR was increased in group HB4 (p < 0.05). The pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK) activities was decreased in group HB4 (p < 0.05). The liver transcriptome suggests that berberine affects carbohydrate metabolic pathways and primary bile acid synthesis pathways. In summary, berberine affects the glucose metabolism in tilapia by altering the intestinal flora structure, enriching differentially expressed genes (DEGs) in the bile acid pathway to stimulate bile acid production so that it promotes glycolysis and inhibits gluconeogenesis. Therefore, 100 mg/kg of berberine supplementation in high-carbohydrate diets is beneficial to tilapia.

Abstract Background Glioma is the most common malignant primary brain tumor and is characterized by a poor prognosis and limited therapeutic options. ISG20 expression is induced by interferons or double-stranded RNA and is associated with poor prognosis in several malignant tumors. Nevertheless, the expression of ISG20 in gliomas, its impact on patient prognosis, and its role in the tumor immune microenvironment have not been fully elucidated. Methods Using bioinformatics, we comprehensively illustrated the potential function of ISG20, its predictive value in stratifying clinical prognosis, and its association with immunological characteristics in gliomas. We also confirmed the expression pattern of ISG20 in glioma patient samples by immunohistochemistry and immunofluorescence staining. Results ISG20 mRNA expression was higher in glioma tissues than in normal tissues. Data-driven results showed that a high level of ISG20 expression predicted an unfavorable clinical outcome in glioma patients, and revealed that ISG20 was possibly expressed on tumor-associated macrophages and was significantly associated with immune regulatory processes, as evidenced by its positive correlation with the infiltration of regulatory immune cells (e.g., M2 macrophages and regulatory T cells), expression of immune checkpoint molecules, and effectiveness of immune checkpoint blockade therapy. Furthermore, immunohistochemistry staining confirmed the enhanced expression of ISG20 in glioma tissues with a higher WHO grade, and immunofluorescence assay verified its cellular localization on M2 macrophages. Conclusions ISG20 is expressed on M2 macrophages, and can serve as a novel indicator for predicting the malignant phenotype and clinical prognosis in glioma patients.

Abstract Synovial sarcoma is a highly malignant tumor that accounts for 10% of all soft tissue sarcomas. Primary pulmonary synovial sarcoma (PPSS) is extremely rare, and its prognosis is poor. A diagnosis is usually established after other primary lung malignancies or metastatic extrathoracic sarcomas have been excluded. Therefore, it is often misdiagnosed. In this study, we report the case of a 38‐year‐old woman who was misdiagnosed as having pleural mesothelioma and finally endured surgery to remove the tumor. The tumor showed SYT‐SSX fusion transcripts and was diagnosed as PPSS after combining histopathological and immunohistochemical analyses. Finally, we determined some biomarkers through whole‐exome sequencing (WES) to improve the diagnosis and treatment strategies.

Abstract Alzheimer's disease (AD) is a neurodegenerative disease with high incidence and widespread attention. There is currently no clear clarification of the pathogenesis. However, ORMDL3 causes ferroptosis in AD, and the potential mechanisms remain unclear. So, this study explore the function of ORMDL3 on ferroptosis in AD and its potential regulatory mechanisms. APPswe/PS1dE9 mice and C57BL/6 mice were induced into the mice model. The murine microglial BV‐2 cells also were induced into the vitro model. In serum samples of AD patients, ORMDL3 mRNA expression levels were upregulated. The serum ORMDL3 levels expression was positively related to the ADL score or MoCA score in AD patients. The serum ORMDL3 expression level was positively related to MMSE score or Hcy levels in AD patients. The mRNA expression of ORMDL3 in the hippocampal tissue of the mice model of AD was upregulated at one, four and eight months. The protein expression of ORMDL3 was upregulated in the mice model of AD. ORMDL3 promoted Alzheimer's disease, and increased oxidative response and ferroptosis in a model of AD. PERK/ATF4/HSPA5 pathway is one important signal pathway for the effects of ORMDL3 in a model of AD. Collectively, these data suggested that ORMDL3 promoted oxidative response and ferroptosis in a model of AD by the PERK/ATF4/HSPA5 pathway, which might be a novel target spot mechanism of ferroptosis in AD and may serve as a regulator of AD‐induced ferroptosis.