Advances in regenerated cellulosic aerogel from waste cotton textile for emerging multidimensional applications.

Rapid development of society and the improvement of people's living standards have stimulated people's keen interest in fashion clothing. This trend has led to the acceleration of new product innovation and the shortening of the lifespan for cotton fabrics, which has resulting in the accumulation of waste cotton textiles. Although cotton fibers can be degraded naturally, direct disposal not only causes a serious resource waste, but also brings serious environmental problems. Hence, it is significant to explore a cleaner and greener waste textile treatment method in the context of green and sustainable development. To realize the high-value utilization of cellulose II aerogel derived from waste cotton products, great efforts have been made and considerable progress has been achieved in the past few decades. However, few reviews systematically summarize the research progress and future challenges of preparing high-value-added regenerated cellulose aerogels via dissolving cotton and other cellulose wastes. Therefore, this article reviews the regenerated cellulose aerogels obtained through solvent methods, summarizes their structure, preparation strategies and application, aimed to promote the development of the waste textile industry and contributed to the realization of carbon neutrality.

Development and evaluation of time-resolved rapid immunofluorescence test for detection of TSOL18 specific antibody in porcine cysticercosis infections.

BACKGROUND: Porcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal Health. The current detection methods of Cysticercus cellulosae cannot meet the needs of large-scale and rapid detection in the field. We hypothesized that the immunofluorescence chromatography test strip (ICS) for detecting Cysticercus cellulosae, according to optimization of a series of reaction systems was conducted, and sensitivity, specificity, and stability testing, and was finally compared with ELISA. This method utilizes Eu3+-labeled time-resolved fluorescent microspheres (TRFM) coupled with TSOL18 antigen to detect TSOL18 antibodies in infected pig sera. RESULTS: ICS and autopsy have highly consistent diagnostic results (n = 133), as determined by Cohen's κ analysis (κ = 0.925). And the results showed that the proposed ICS are high sensitivity (0.9459) with specificity (0.9792). The ICS was unable to detect positive samples of other parasites. It can be stored for at least six months at 4℃. CONCLUSIONS: In summary, we established a TRFM-ICS method with higher sensitivity and specificity than indirect ELISA. Results obtained from serum samples can be read within 10 min, indicating a rapid, user-friendly test suitable for large-scale field detection.

Identification of immunogenic cell death-related damage-related molecular patterns (DAMPs) to predict outcomes in patients with head and neck squamous cell carcinoma.

PURPOSE: Head and neck cancer is the sixth most common type of cancer worldwide, wherein the immune responses are closely associated with disease occurrence, development, and prognosis. Investigation of the role of immunogenic cell death-related genes (ICDGs) in adaptive immune response activation may provide cues into the mechanism underlying the outcome of HNSCC immunotherapy. METHODS: ICDGs expression patterns in HNSCC were analyzed, after which consensus clustering in HNSCC cohort conducted. A 4-gene prognostic model was constructed through LASSO and Cox regression analyses to analyze the prognostic index using the TCGA dataset, followed by validation with two GEO datasets. The distribution of immune cells and the response to immunotherapy were compared between different risk subtypes through multiple algorithms. Moreover, immunohistochemical (IHC) analyses were conducted to validate the prognostic value of HSP90AA1 as a predictor of HNSCC patient prognosis. In vitro assays were performed to further detect the effect of HSP90AA1 in the development of HNSCC. RESULTS: A novel prognostic index based on four ICDGs was constructed and proved to be useful as an independent factor of HNSCC prognosis. The risk score derived from this model grouped patients into high- and low-risk subtypes, wherein the high-risk subtype had worse survival outcomes and poorer immunotherapy response. IHC analysis validated the applicability of HSP90AA1 as a predictor of prognosis of HNSCC patients. HSP90AA1 expression in tumor cells promotes the progression of HNSCC. CONCLUSIONS: Together, these results highlight a novel four-gene prognostic signature as a valuable tool to assess survival status and prognosis of HNSCC patients.

Protocol for survival assay of Caenorhabditis elegans to Pseudomonas aeruginosa PA14 infection.

The nematode Caenorhabditis elegans is a powerful model organism for studying the molecular and cellular mechanisms of innate immunity governed by the intestine. Here, we present a protocol to perform C. elegans survival assays to infection by the bacterial pathogen Pseudomonas aeruginosa PA14. Specifically, we describe steps for preparing C. elegans strains and PA14 bacteria for survival assays. This protocol will assist researchers to study genes involved in intestinal innate immunity and gut defense against pathogen infection. For complete details on the use and execution of this protocol, please refer to Liu et al.1 and Zheng et al.2.

Neutrophil extracellular traps promote invasion and metastasis via NLRP3-mediated oral squamous cell carcinoma pyroptosis inhibition.

Neutrophil extracellular traps (NETs) are reticular structures composed of neutrophil elastase (NE), cathepsin G (CG) and DNA-histone enzyme complexes. Accumulating evidence has revealed that NETs play important roles in tumor progression, metastasis, and thrombosis. However, our understanding of its clinical value and mechanism of action in oral squamous cell carcinoma (OSCC) is limited and has not yet been systematically described. Here, we aimed to investigate the clinical significance of NETs in OSCC and the mechanisms by which they affect its invasive and metastatic capacity. Our results demonstrated that high enrichment of NETs is associated with poor prognosis in OSCC, and mechanistic studies have shown that NE in NETs promotes invasion and metastasis via NLRP3-mediated inhibition of pyroptosis in OSCC. These findings may provide a new therapeutic approach for OSCC.

The possible causal relationship between COVID-19 and imaging markers of cerebral small vessel disease: a Mendelian randomization study.

OBJECTIVES: Observational studies have suggested that SARS-CoV-2 infection may increase the burden of cerebral small vessel disease (CSVD). This study aims to explore the causal correlation between COVID-19 and the imaging markers of CSVD using Mendelian randomization (MR) methods. METHODS: Summary-level genome-wide association study (GWAS) statistics for COVID-19 susceptibility, hospitalization, and severity were utilized as proxies for exposure. Large-scale meta-analysis GWAS data on three neuroimaging markers of white matter hyperintensity, lacunar stroke, and brain microbleeds, were employed as outcomes. Our primary MR analysis employed the inverse variance weighted (IVW) approach, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. We also conducted multivariable MR analysis to address confounding bias and validate the robustness of the established causal estimates. Comprehensive sensitivity analyses included Cochran's Q test, Egger-intercept analysis, MR-PRESSO, and leave-one-out analysis. RESULTS: The MR analysis revealed a significant causal correlation between the severity of COVID-19 and an increased risk of lacunar stroke, as demonstrated by the IVW method (ORivw = 1.08, 95% CI: 1.03-1.16, pivw = 0.005, FDR = 0.047). Nevertheless, no causal correlations were observed between COVID-19 susceptibility or hospitalization and any CSVD imaging markers. The robustness and stability of these findings were further confirmed by multivariable MR analysis and comprehensive sensitivity analyses. DISCUSSION: This study provides compelling evidence of a potential causal effect of severe COVID-19 on the incidence of lacunar stroke, which may bring fresh insights into the understanding of the comorbidity between COVID-19 and CSVD.

Identification and Characterization of long non-coding RNAs in Mammary Gland Tissues of Chinese Holstein Cows.

LncRNAs (Long non-coding RNA) is an RNA molecule with a length more than 200bp. LncRNAs can directly act on mRNA, thus affecting the expression of downstream target genes and proteins, and widely participate in many important physiological and pathological regulation processes of the body. In this study, RNA-Seq was performed to detect lncRNAs from mammary gland tissues of 3 Chinese Holstein cows, including 3 cows at 7 days before calving and the same 3 cows at 30 days postpartum (early lactation stage). A total of 1,905 novel lncRNAs were detected, 57.3% of the predicted lncRNAs are ≥ 500bp and 612 lncRNAs are intronic lncRNAs. The exon number of lncRNAs ranged from 2 to 10. A total of 96 lncRNAs were significantly differentially expressed between two stages, which 47 were upregulated and 49 were downregulated. Pathway analysis found that target genes were mainly concentrated on the ECM-receptor interaction, Jak-STAT signaling pathway, PI3K-Akt signaling pathway and TGF-beta signaling pathway. This study revealed the expression profile and characteristics of lncRNAs in the mammary gland tissues of Holstein cows at non-lactation and early lactation period, and providing a basis for studying the functions of lncRNAs in Holstein cows during different lactation periods.

Ultrasensitive Detection of Prostate Specific Antigen by an Unlabeled Fluorescence Aptasensor Based on the AIE Effect.

The accurate and sensitive detection of prostate specific antigen (PSA) is vital for the early diagnosis and treatment of prostate cancer. To this end, an unlabeled fluorescent aptasensor was constructed by using a novel Compound B {1,1'-(1,4-phenylene) bis(3-ethyl-1H-imidazol-3-ium) iodide} with aggregation-induced emission (AIE) activity as a fluorescence signal and NH2-Fe3O4 particle as an adsorption platform. Compound B could combine with prostate specific antigen aptamers (PSA-Apt) to form a PSA-Apt/B complex, which further generated the AIE effect. Then, PSA was added to the PSA-Apt/B solution. PSA combined with PSA-Apt/B to form the PSA-Apt/B/PSA complex. Next, NH2-Fe3O4 magnetic particles were added to the solution. Given that PSA-Apt/B/PSA would no longer combine with NH2-Fe3O4 magnetic particles, the PSA-Apt/B/PSA complex remained in the supernate after magnet separation, and the supernate showed strong fluorescence (I). When no PSA was added to the PSA-Apt/B solution, PSA-Apt/B could combine with NH2-Fe3O4 magnetic particles and would be sucked into the bottom of the test tube by magnet, and the supernate would show weak fluorescence (I0). Result showed that the difference between the above-mentioned two fluorescence values (∆I = I - I0) had an excellent linear relationship with the PSA concentration within the concentration range of 0.01-10 ng/mL, and its limit of detection was 3 pg/mL (S/N = 3). In addition, the sensor has high accuracy and can be directly used to test PSA in actual serum samples.

The causal relationship between sarcopenia-related traits and ischemic stroke: Insights from univariable and multivariable Mendelian randomization analyses.

AIMS: The causal relationship between sarcopenia-related traits and ischemic stroke (IS) remains poorly understood. This study aimed to explore the causal impact of sarcopenia-related traits on IS and to identify key mediators of this association. METHODS: We conducted univariable, multivariable two-sample, and two-step Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. This included data for appendicular lean mass (ALM), hand grip strength (HGS), and usual walking pace (UWP) from the UK Biobank, and IS data from the MEGASTROKE consortium. Additionally, 21 candidate mediators were analyzed based on their respective GWAS data sets. RESULTS: Each 1-SD increase in genetically proxied ALM was associated with a 7.5% reduction in the risk of IS (95% CI: 0.879-0.974), and this correlation remained after controlling for levels of physical activity and adiposity-related indices. Two-step MR identified that six mediators partially mediated the protective effect of higher ALM on IS, with the most significant being coronary heart disease (CHD, mediating proportion: 39.94%), followed by systolic blood pressure (36.51%), hypertension (23.87%), diastolic blood pressure (15.39%), type-2 diabetes mellitus (T2DM, 12.71%), and low-density lipoprotein cholesterol (7.97%). CONCLUSION: Our study revealed a causal protective effect of higher ALM on IS, independent of physical activity and adiposity-related indices. Moreover, we found that higher ALM could reduce susceptibility to IS partially by lowering the risk of vascular risk factors, including CHD, hypertension, T2DM, and hyperlipidemia. In brief, we elucidated another modifiable factor for IS and implied that maintaining sufficient muscle mass may reduce the risk of such disease.

Bone marrow stromal cells dictate lanosterol biosynthesis and ferroptosis of multiple myeloma.

Ferroptosis has been demonstrated a promising way to counteract chemoresistance of multiple myeloma (MM), however, roles and mechanism of bone marrow stromal cells (BMSCs) in regulating ferroptosis of MM cells remain elusive. Here, we uncovered that MM cells were more susceptible to ferroptotic induction under the interaction of BMSCs using in vitro and in vivo models. Mechanistically, BMSCs elevated the iron level in MM cells, thereby activating the steroid biosynthesis pathway, especially the production of lanosterol, a major source of reactive oxygen species (ROS) in MM cells. We discovered that direct coupling of CD40 ligand and CD40 receptor constituted the key signaling pathway governing lanosterol biosynthesis, and disruption of CD40/CD40L interaction using an anti-CD40 neutralizing antibody or conditional depletion of Cd40l in BMSCs successfully eliminated the iron level and lanosterol production of MM cells localized in the Vk*MYC Vk12653 or NSG mouse models. Our study deciphers the mechanism of BMSCs dictating ferroptosis of MM cells and highlights the therapeutic potential of non-apoptosis strategies for managing refractory or relapsed MM patients.

Evaluation of probiotics in the treatment of hypothyroidism in early pregnancy combined with small intestinal bacterial overgrowth.

The aim of this study was to investigate the association between hypothyroidism in early pregnancy and small intestinal bacterial overgrowth (SIBO) and the effect of probiotics. Patients with hypothyroidism in early pregnancy and normal pregnant women during the same period were included in the methane-hydrogen breath test to compare the incidence of SIBO, smoothed curve fit, and differences in clinical symptoms. For those who combined with SIBO, the rate of clinical symptom conversion, thyroid hormones, and changes in associated inflammatory indexes were compared after 21 days of treatment with probiotics on top of conventional levothyroxine sodium tablets. The results are as follows: (1) The incidence of combined SIBO in patients with hypothyroidism in pregnancy was 56.0%, significantly higher than the 28.0% of normal pregnant women during the same period. (2) The highest value of hydrogen plus methane gas in 90 min in pregnancy hypothyroid patients showed a significant negative correlation with FT4 (p < .001, SD = 0.169). (3) Abdominal distension symptoms were significantly increased in both groups after combined SIBO (p = .036, p = .025), and the conversion rate after treatment was 69.2% and 75.0%, respectively. (4) In hypothyroidism, pregnancy combined with SIBO, TSH, and CRP was higher before treatment (p = .001, p = .012) and decreased significantly after treatment (p = .001, p = .008). Hypothyroidism in early pregnancy is associated with SIBO, and probiotic treatment is significantly effective.

FADD promotes type I interferon production to suppress porcine reproductive and respiratory syndrome virus infection.

Porcine reproductive and respiratory syndrome (PRRS) is an epidemic animal infectious disease worldwide, causing huge economic losses to the global swine industry. Fas-associated death domain (FADD) was previously reported to be an adaptor protein that functions in transferring the apoptotic signals regulated by the death receptors. In the current study, we unravel its unidentified role in promoting type I interferon (IFN) production during PRRS virus (PRRSV) infection. We identified that FADD inhibited PRRSV infection via promotion of type I IFN transcription. Overexpression of FADD suppressed the replication of PRRSV, while knockout of FADD increased viral titer and nucleocapsid protein expression. Mechanistically, FADD promoted mitochondrial antiviral signaling protein (MAVS)-mediated production of IFN-ß and some IFN-stimulated genes (ISGs). Furthermore, FADD exerted anti-PRRSV effects in a MAVS-dependent manner and increased the type I IFN signaling during PRRSV infection. This study highlights the importance of FADD in PRRSV replication, which may have implications for the future control of PRRS.

CMYC-initiated HNF1A-AS1 overexpression maintains the stemness of gastric cancer cells.

Cancer stem cells (CSCs) are believed to be responsible for cancer metastasis and recurrence due to their self-renewal ability and resistance to treatment. However, the mechanisms that regulate the stemness of CSCs remain poorly understood. Recently, evidence has emerged suggesting that long non-coding RNAs (lncRNAs) play a crucial role in regulating cancer cell function in different types of malignancies, including gastric cancer (GC). However, the specific means by which lncRNAs regulate the function of gastric cancer stem cells (GCSCs) are yet to be fully understood. In this study, we investigated a lncRNA known as HNF1A-AS1, which is highly expressed in GCSC s and serves as a critical regulator of GCSC stemness and tumorigenesis. Our experiments, both in vitro and in vivo, demonstrated that HNF1A-AS1 maintained the stemness of GC cells. Further analysis revealed that HNF1A-AS1, transcriptionally activated by CMYC, functioned as a competing endogenous RNA by binding to miR-150-5p to upregulate ß-catenin expression. This in turn facilitated the entry of ß-catenin into the nucleus to activate the Wnt/ß-catenin pathway and promote CMYC expression, thereby forming a positive feedback loop that sustained the stemness of GCSCs. We also found that blocking the Wnt/ß-catenin pathway effectively inhibited the function of HNF1A-AS1, ultimately resulting in the inhibition of GCSC stemness. Taken together, our results demonstrated that HNF1A-AS1 is a regulator of the stemness of GCSCs and could serve as a potential marker for targeted GC therapy.

Tacrolimus alleviates pulmonary fibrosis progression through inhibiting the activation and interaction of ILC2 and monocytes.

Idiopathic pulmonary fibrosis (IPF) is a heterogeneous group of lung diseases with different etiologies and characterized by progressive fibrosis. This disease usually causes pulmonary structural remodeling and decreased pulmonary function. The median survival of IPF patients is 2-5 years. Predominantly accumulation of type II innate immune cells accelerates fibrosis progression by secreting multiple pro-fibrotic cytokines. Group 2 innate lymphoid cells (ILC2) and monocytes/macrophages play key roles in innate immunity and aggravate the formation of pro-fibrotic environment. As a potent immunosuppressant, tacrolimus has shown efficacy in alleviating the progression of pulmonary fibrosis. In this study, we found that tacrolimus is capable of suppressing ILC2 activation, monocyte differentiation and the interaction of these two cells. This effect further reduced activation of monocyte-derived macrophages (Mo-M), thus resulting in a decline of myofibroblast activation and collagen deposition. The combination of tacrolimus and nintedanib was more effective than either drug alone. This study will reveal the specific process of tacrolimus alleviating pulmonary fibrosis by regulating type II immunity, and explore the potential feasibility of tacrolimus combined with nintedanib in the treatment of pulmonary fibrosis. This project will provide new ideas for clinical optimization of anti-pulmonary fibrosis drug strategies.

A triple-crosslinking strategy for high-performance regenerated cellulose fibers derived from waste cotton textiles.

Regenerated cellulose fibers has attracted increasing attention for high-grade textile raw materials and industrial textiles, but the low mechanical property caused by differences in regenerated raw materials and production levels limits its commercial application in the product diversity. Herein, we proposed a novel triple-crosslinking strategy by coupling with hydrogen bonds, chemical crosslinking, and internal mineralization from multiple pulsed vapor phase infiltration (MPI) to improve the mechanical performance of regenerated cellulose fibers. A binary solvent composed of ionic liquid (IL) and dimethyl sulfoxide (DMSO) is used to dissolve waste cotton textile and then wet spinning. Dual-crosslinking is firstly achieved by coupling glutaraldehyde (GA) and cellulose reaction. Subsequently, a metal oxide is intentionally infiltrated into inner cellulosic through MPI technology to form a third form of crosslinking, accompanied by the ultra-thin metal oxide nano-layer onto the surface of regenerated cellulose fibers. Results showed that the triple-crosslinking strategy has increased the tensile stress of the fiber by 43.57 % to 287.03 MPa. In all, triple-crosslinking strategy provides a theoretical basis and technical approach for the reinforcement of weak fibers in waste cotton recycling, which is expected to accelerate the development of the waste textile recycling industry and promote of the added-value of regenerated products.

Anti-Cancer Potency of Copper-Doped Carbon Quantum Dots Against Breast Cancer Progression.

Introduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations. Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells. Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway. Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.

DNA methylation haplotype block signatures responding to Staphylococcus aureus subclinical mastitis and association with production and health traits.

BACKGROUND: DNA methylation has been documented to play vital roles in diseases and biological processes. In bovine, little is known about the regulatory roles of DNA methylation alterations on production and health traits, including mastitis. RESULTS: Here, we employed whole-genome DNA methylation sequencing to profile the DNA methylation patterns of milk somatic cells from sixteen cows with naturally occurring Staphylococcus aureus (S. aureus) subclinical mastitis and ten healthy control cows. We observed abundant DNA methylation alterations, including 3,356,456 differentially methylated cytosines and 153,783 differential methylation haplotype blocks (dMHBs). The DNA methylation in regulatory regions, including promoters, first exons and first introns, showed global significant negative correlations with gene expression status. We identified 6435 dMHBs located in the regulatory regions of differentially expressed genes and significantly correlated with their corresponding genes, revealing their potential effects on transcriptional activities. Genes harboring DNA methylation alterations were significantly enriched in multiple immune- and disease-related pathways, suggesting the involvement of DNA methylation in regulating host responses to S. aureus subclinical mastitis. In addition, we found nine discriminant signatures (differentiates cows with S. aureus subclinical mastitis from healthy cows) representing the majority of the DNA methylation variations related to S. aureus subclinical mastitis. Validation of seven dMHBs in 200 cows indicated significant associations with mammary gland health (SCC and SCS) and milk production performance (milk yield). CONCLUSIONS: In conclusion, our findings revealed abundant DNA methylation alterations in milk somatic cells that may be involved in regulating mammary gland defense against S. aureus infection. Particularly noteworthy is the identification of seven dMHBs showing significant associations with mammary gland health, underscoring their potential as promising epigenetic biomarkers. Overall, our findings on DNA methylation alterations offer novel insights into the regulatory mechanisms of bovine subclinical mastitis, providing further avenues for the development of effective control measures.

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis.

BACKGROUND: Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry. Multi-omics approaches enable the comprehensive investigation of the complex interactions between multiple layers of information to provide a more holistic view of disease pathogenesis. Therefore, this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data (mRNA and lncRNA), small RNA sequencing data (miRNA) and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes. RESULTS: Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis, provided further insights into subclinical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis. The abundant genomic and epigenomic signatures with significant alterations related to subclinical mastitis were observed, including 30,846, 2552, 1276 and 57 differential methylation haplotype blocks (dMHBs), differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs), respectively. Next, 5 factors presenting the principal variation of differential multi-omics signatures were identified. The important roles of Factor 1 (DEG, DEM and DEL) and Factor 2 (dMHB and DEM), in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed. Each of the omics within Factors 1 and 2 explained about 20% of the source of variation in subclinical mastitis. Also, networks of important functional gene sets with the involvement of multi-omics signatures were demonstrated, which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastitis. Furthermore, multi-omics integration enabled the association of the epigenomic regulatory factors (dMHBs, DELs and DEMs) of altered genes in important pathways, such as 'Staphylococcus aureus infection pathway' and 'natural killer cell mediated cytotoxicity pathway', etc., which provides further insights into mastitis regulatory mechanisms. Moreover, few multi-omics signatures (14 dMHBs, 25 DEGs, 18 DELs and 5 DEMs) were identified as candidate discriminant signatures with capacity of distinguishing subclinical mastitis cows from healthy cows. CONCLUSION: The integration of genomic and epigenomic data by multi-omics approaches in this study provided a better understanding of the molecular mechanisms underlying subclinical mastitis and identified multi-omics candidate discriminant signatures for subclinical mastitis, which may ultimately lead to the development of more effective mastitis control and management strategies.

FTO Stabilizes MIS12 to Inhibit Vascular Smooth Muscle Cell Senescence in Atherosclerotic Plaque.

Purpose: Atherosclerosis is the main cause of atherosclerotic cardiovascular disease (CVD). Here, we aimed to uncover the role and mechanisms of fat mass and obesity-associated genes (FTO) in the regulation of vascular smooth muscle cell (VSMC) senescence in atherosclerotic plaques. Methods: ApoE-/- mice fed a high-fat diet (HFD) were used to establish an atherosclerotic animal model. Immunohistochemistry, and the staining of hematoxylin-eosin, Oil Red O, Sirius red, and Masson were performed to confirm the role of FTO in atherosclerosis in vivo. Subsequently, FTO expression in primary VSMCs is either upregulated or downregulated. Oxidized low-density lipoprotein (ox-LDL) was used to treat VSMCs, followed by EdU staining, flow cytometry, senescence-associated ß-galactosidase (SA-ß-gal) staining, immunofluorescence, telomere detection, RT-qPCR, and Western blotting to determine the molecular mechanisms by which FTO inhibits VSMC senescence. Results: Decreased FTO expression was observed in progressive atherosclerotic plaques of ApoE-/- mice fed with HFD. FTO upregulation inhibits atherosclerotic lesions in mice. FTO inhibits VSMC aging in atherosclerotic plaques by helping VSMC withstand ox-LDL-induced cell cycle arrest and senescence. This process is achieved by stabilizing the MIS12 protein in VSMC through a proteasome-mediated pathway. Conclusion: FTO inhibits VSMC senescence and subsequently slows the progression of atherosclerotic plaques by stabilizing the MIS12 protein.

Construction, characterization and bioactivity evaluation of curcumin nanocrystals with extremely high solubility and dispersion prepared by ultrasound-assisted method.

Curcumin (Cur) as a natural pigment and biological component, can be widely used in food and beverages. However, the water insolubility of Cur significantly limits its applications. In this study, we prepared a series of nanocrystals via ultrasound-assisted method to improve the solubility and availability of Cur. The results showed artemisia sphaerocephala krasch polysaccharide (ASKP), gum arabic (GA) and wheat protein (WP) were outstanding stabilizers for nanocryatals except traditional agent, poloxamer 188 (F68). The obtained curcumin nanocrystals (Cur-NC) displayed a rod-shaped, crystal- and nanosized structure, and extremely high loading capacity (more over 80 %, w/w). Compared with raw powder, Cur-NC greatly improved the water solubility and dispersibility, and the slow and complete release of Cur of Cur-NC also endowed them excellent antioxidant capacities even at 10 µg/mL. Importantly, as functional factor additive in beverages (e.g. water and emulsion), Cur-NC could increase the content of Cur to at least 600 µg/mL and retain a good stability. Overall, we provided an effective improvement method for the liposoluble active molecules (e.g. Cur) based on the nanocrystals, which not only tremendously enhanced its water solubility, but also strengthened its bioactivity. Notably, our findings broadened the application of water-insoluble compounds.