Histological and molecular difference in albumen quality between post-adolescent hens and aged hens.

The decline in albumen quality resulting from aging hens poses a threat to the financial benefits of the egg industry. Exploring the underlying mechanisms from the perspective of cell molecules of albumen formation is significant for the efficient regulation of albumen quality. Two individual groups of Hy-Line Brown layers with ages of 40 (W40) and 100 (W100) wk old were used in the present study. Each group contained over 2,000 birds. This study assessed the egg quality, biochemical indicators and physiological status of hens between W40 and W100. Subsequently, a quantitative proteomic analysis was conducted to identify differences in protein abundance in magnum tissues between W40 and W100. In the W40 group, significant increases (P < 0.05) were notable for albumen quality (thick albumen solid content, albumen height, Haugh unit), serum indices (calcium, estrogen, and progesterone levels), magnum histomorphology (myosin light-chain kinase content, secretory capacity, mucosal fold, goblet cell count and proportion) as well as the total antioxidant capacity of the liver. However, the luminal diameter of the magnum, albumen gel properties and random coil of the albumen were increased (P < 0.05) in the W100 group. The activity of glutathione, superoxidase dismutase, and malondialdehyde in the liver, magnum, and serum did not vary (P > 0.05) among the groups. Proteomic analysis revealed the identification of 118 differentially expressed proteins between the groups, which comprised proteins associated with protein secretion, DNA damage and repair, cell proliferation, growth, antioxidants, and apoptosis. Furthermore, Kyoto Encyclopedia of Genes pathway analysis revealed that BRCA2 and FBN1 were significantly downregulated in Fanconi anemia (FA) and TGF-ß signaling pathways in W100, validated through quantitative real-time PCR (qRT-PCR). In conclusion, significant age-related variations in albumen quality, and magnum morphology are regulated by proteins involved in antioxidant capacity.

Associations between physical activity and all-cause and cardiovascular mortality in adults with type 2 diabetes mellitus: A prospective cohort study from NHANES 2007-2018.

AIMS: To investigate the dose-response association between physical activity and all-cause and cardiovascular mortality in adults with type 2 diabetes mellitus and the effects of replacing sedentary behavior with physical activity. METHODS: 4808 adults with type 2 diabetes mellitus were included in NHANES 2007-2018. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. Isotemporal substitution analyses were further to determine the possible benefit of replacing sedentary time. RESULTS: During a median follow-up of 6.58 years, 902 deaths occurred, including 290 deaths from cardiovascular disease. Compared with the inactive group, the low-active and high-active groups were associated with declined risks of all-cause mortality [HRs (95% CIs) 0.64 (0.50, 0.83); 0.60 (0.50, 0.73), respectively] and cardiovascular mortality [0.50 (0.29, 0.88); 0.54 (0.39, 0.76)), respectively]. Dose-response analysis showed a significant U-shaped curve between physical activity and all-cause and cardiovascular mortality. Replacing 30 min/day of sedentary time with physical activity was substantially linked to a reduced risk of 8-32% mortality. CONCLUSION: A high level of PA of 40.52 and 31.66 MET-h/week was respectively related to the lowest risk of all-cause and cardiovascular mortality. Replacing sedentary time with physical activity could benefit the type 2 diabetes mellitus population.

Tumor-derived exosomal linc00881 induces lung fibroblast activation and promotes osteosarcoma lung migration.

Osteosarcoma (OS) commonly metastasizes to the lung, yet the underlying molecular mechanisms remain poorly understood. Exosomes play a crucial role in tumor migration, including OS lung migration. However, the underlying mechanism by which exosome-derived long non-coding RNAs (lncRNAs) contribute to lung migration in osteosarcoma (OS) remains unclear. This study presents a newly discovered lncRNA, linc00881, derived from OS exosomes. Our study shows that linc00881 promotes the migration of OS cells to the lung and induces the conversion of normal lung fibroblasts into cancer-associated fibroblasts (CAFs). Subsequently, we found that exosomal linc00881 secreted by OS cells can regulate the expression of matrix metalloproteinase 2 (MMP2) in HFL-1 cells by sponging miR-29c-3p, thereby activating the NF-κB signaling in lung fibroblasts. Finally, we discovered that pro-inflammatory cytokines, namely IL-1ß, IL-6, and IL-8, were secreted through the linc00881/miR-29c-3p/MMP2 axis. These results suggest that OS-derived exosomes can mediate the intercellular crosstalk between OS cells and lung fibroblasts, ultimately impacting OS lung migration. Our study provides a potential target for the treatment of OS lung migration.

Andrographolide inhibits infectious bronchitis virus-induced apoptosis, pyroptosis, and inflammation.

BACKGROUND: Avian infectious bronchitis virus (IBV), a coronavirus, causes a huge economic loss to the poultry industry. Andrographolide (APL) is a compound with a variety of pharmacological properties, including antiviral and anti-inflammatory effects. In this study, APL was evaluated for antiviral activity by its anti-apoptotic, anti-pyroptosis, and anti-inflammatory effects. METHODS: The cytotoxicity of APL was determined by the MTT method. We investigated the therapeutic impact of APL on IBV through a plate assay. We explored that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation in HD11 cells by RT-qPCR and immunofluorescence. Also, it was verified in the clinical chicken embryo trial. RESULTS: We found that APL down-regulated apoptosis-related genes Caspase-3, Caspase-8, Caspase-9, Bax, Bid, and Bak, down-regulated pyroptosis gene DFNA5, and down-regulated inflammation-related genes (NF-κB, NLRP3, iNOS, TNF-α, and IL-1ß). In addition, APL reduced the reactive oxygen species (ROS) production in cells. Finally, clinical trials showed that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation, as well as reduced the mortality and malformation of chicken embryos. CONCLUSIONS: In this study, we delved into the antiviral properties of APL in the context of chicken macrophage (HD11) infection with IBV. Our findings confirm that andrographolide effectively inhibits apoptosis, pyroptosis, and inflammation by IBV infection. Furthermore, this inhibition was verified on chicken embryos in vivo. This inhibition suggests a substantial potential for APL as a therapeutic agent to mitigate the harmful effects of IBV on host cells.

Effects of Dietary Rare Earth Chitosan Chelate on Performance, Egg Quality, Immune and Antioxidant Capacity, and Intestinal Digestive Enzyme Activity of Laying Hens.

Rare earth chitosan chelate salt (RECC) is a potential feed additive and is a product of the chelation effect between rare earth ions and chitosan. This research study aims to explore the effects of dietary RECC on performance, egg quality, intestinal digestive function, and the immune and antioxidant capacity of laying hens in the late phase of production. A total of 360 56-week-old Dawu Jinfeng laying hens were randomly allotted into four treatment groups with six replicates per treatment and 15 birds per replicate. The laying hens were fed the basal diet supplemented with, respectively, 0 (control: CON), 100 (R1), 200 (R2), and 400 (R3) mg/kg for 8 weeks. Dietary RECC significantly improved average daily feed intake (ADFI) and average daily egg yield in both linear and quadratic manner (p < 0.05). In addition, albumen height and HU were improved significantly (p < 0.05) in a dose-dependent manner of RECC. In addition, a significant decrease (p < 0.05) in serum TP, IgA, and MDA for the R1 group and IgG in the R2 group were notable, while the increase in serum TP and decrease in T-AOC were found for R3 dietary group compared to CON (p < 0.05). The level of intestinal IL-2 and TNF-α was decreased by dietary RECC (p < 0.01). The activities of the digestive enzyme (α-Amylase, lipase, and Trypsin) showed a quadratic change with an increase and then decrease in response to increasing dose of RECC, 200 mg/kg RECC significantly increased the activity of lipase and Trypsin (p < 0.01). Supplementation of dietary RECC at low doses compared to higher doses impacted positive effects on the antioxidant capacity and immune function (p < 0.05). The utilization of RECC as a feed additive in the diet of aged laying hens exerted beneficial effects on egg production, albumen quality, humoral immunity, inflammatory response, and activity of digestive enzymes. Thus, the regulation of antioxidant capacity and duodenal function via increased enzyme activity and immune and inflammatory response were critical to the improvement of laying performance and egg quality in aged hens. The optimal supplemental dose is 100-200 mg/kg.

Glycosylated proteins with abnormal glycosylation changes are potential biomarkers for early diagnosis of breast cancer.

Conventional cancer management relies on tumor type and stage for diagnosis and treatment, which leads to recurrence and metastasis and death in young women. Early detection of proteins in the serum aids diagnosis, progression, and clinical outcomes, possibly improving survival rate of breast cancer patients. In this review, we provided an insight into the influence of aberrant glycosylation on breast cancer development and progression. Examined literatures revealed that mechanisms underlying glycosylation moieties alteration could enhance early detection, monitoring, and therapeutic efficacy in breast cancer patients. This would serve as a guide for the development of new serum biomarkers with higher sensitivity and specificity, providing possible serological biomarkers for breast cancer diagnosis, progression, and treatment.

Intramedullary nail fixation assisted by locking plate for complex subtrochanteric femur fractures: A retrospective study.

BACKGROUND: This study aims to compare therapeutic effects of two methods in complicated subtrochanteric femur fractures surgery: intramedullary nail fixation assisted with lateral monocortical locking plate versus intramedullary nail fixation assisted with supplementary cables. METHODS: From June 2015 to June 2020, seventy-seven patients with complex subtrochanteric fractures (i.e., Seinsheimer's classification type IV or V) were included in this study. Thirty-six patients (plate group) were operated using the intramedullary nail fixation assisted by lateral monocortical locking plate, and forty-one patients (cable group) were using the intramedullary nail fixation assisted by cables. The clinical information and demographic results were collected and compared. RESULTS: Operation time of plate group was shorter than cable group and the Incisions length of plate group was longer. The fluoroscopy times were 22.8 ± 8.2 in plate group and 33.0 ± 9.0 in cable group (p < 0.01). Compared with the cable group, patients in plate group used less cerclage cables (p < 0.01). Patients in the plate group has less medial cortex displacement compared with the cable group. (p = 0.038). As for the angular difference of neck shaft angle between operated hip and uninjured hip, plate group has less difference compared with the cable group. Time to union was 14.2 ± 3.1 weeks in plate group which is shorter than the cable group (17.9 ± 4.8 weeks). In terms of follow up period, number of malunion, Harris hip score, walking ability and traumatic hip rating scale, no significant differences were detected. CONCLUSIONS: Our results suggest that using lateral monocortical plate as an auxiliary way may have a longer surgical incision and more intraoperative blood loss, however, the operation time is shorter, the fluoroscopy times is less, and the time to union is shorter. Intramedullary nail fixation assisted by lateral monocortical locking plate may be a new option for patients with complex subtrochanteric femur fractures.

ZnO/Cu2O heterojunction integrated fiber-optic biosensor for remote detection of cysteine.

Indium tin oxide, semiconductor nanomaterial ZnO, and Cu2O were first loaded on the surface of the optical fiber to form an optical fiber probe. Large-volume macroscopic spatial light is replaced by an optical fiber path, and remote light injection is implemented. Based on the optical fiber probe, a photoelectrochemical biosensor was constructed and remote detection of cysteine was realized. In this tiny device, the optical fiber probe not only acts as a working electrode to react with the analyte but also directs the light exactly where it is needed. Simultaneously, the electrochemical behavior of cysteine on the surface of the working electrode is dominated by diffusion-control, which provides strong support for quantitative detection. Then, under the bias potential of 0 V, the linear range of the fiber-optic-based cysteine biosensor was 0.01∼1 µM, the regression coefficient (R2) value was 0.9943. In spiked synthetic urine, the detection of cysteine was also realized by the integrated biosensor. Moreover, benefiting from the low optical fiber loss, the new structure also possesses a unique remote detection function. This work confirms that photoelectrochemical biosensors can be integrated via optical fibers and retain comparable sensing performance. Based on this property, different materials can also be loaded on the surface of the optical fiber for remote detection of other analytes. It is expected to facilitate the research on fiber-optic-based integrated biosensors and show application prospects in diverse fields such as biochemical analysis and disease diagnosis.

Calponin 1 increases cancer-associated fibroblasts-mediated matrix stiffness to promote chemoresistance in gastric cancer.

The mechanical microenvironment regulated by cancer-associated fibroblasts (CAFs) influence tumor progression. Chemotherapeutic interventions including 5-Fluorouracil (5-Fu) are commonly used for primary treatment of patients with advanced gastric cancer (GC), and the development of acquired resistance to 5-Fu limits the clinical efficacy of these chemotherapies. However, if and how the interplay between CAFs and the mechanical microenvironment regulates GC response to 5-Fu is poorly understood. In this study, we demonstrate that high-level expression of calponin 1(CNN1) in gastric CAFs predicts poor clinical outcomes of GC patients, especially for those treated with 5-Fu. CNN1 knockdown in CAFs improves the effectiveness of 5-Fu in reducing tumor growth in a mouse GC model and confers increased sensitivity to 5-Fu in a 3D culture system. Furthermore, CNN1 knockdown impairs CAF contraction and reduces matrix stiffness without affecting the expression of matrix proteins. Mechanistically, CNN1 interacts with PDZ and LIM Domain 7 (PDLIM7) and prevents its degradation by the E3 ubiquitin ligase NEDD4-1, which leads to activation of the ROCK1/MLC pathway. The increased matrix stiffness, in turn, contributes to 5-Fu resistance in GC cells by activating YAP. Taken together, our data reveal a critical role of the mechanical microenvironment in 5-Fu resistance, which is modulated by CNN1hi CAFs-mediated matrix stiffening, indicating that targeting CAFs may provide a novel option for overcoming drug resistance in GC.

Regulation of bone health through physical exercise: Mechanisms and types.

Osteoporosis, characterized by bone mineral density reduction, bone mass loss, increased bone fragility, and propensity to fractures, is a common disease in older individuals and one of the most serious health problems worldwide. The imbalance between osteoblasts and osteoclasts results in the predominance of bone resorption and decreased bone formation. In recent years, it has been found that regular and proper exercise not only helps prevent the occurrence of osteoporosis but also adds benefits to osteoporosis therapy; accordingly, bone homeostasis is closely associated with mechanical stress and the intricate crosstalk between osteoblasts and osteoclasts. In this review, we summarize the mechanisms of exercise on osteoporosis and provide new proposals for the prevention and treatment of osteoporosis.

Prognostic characteristics of immune subtypes associated with acute myeloid leukemia and their identification in cell subsets based on single-cell sequencing analysis.

Immune genes play an important role in the development and progression of acute myeloid leukemia (AML). However, the role of immune genes in the prognosis and microenvironment of AML remains unclear. In this study, we analyzed 151 AML patients in the TCGA database for relevant immune cell infiltration. AML patients were divided into high and low immune cell infiltration clusters based on ssGSEA results. Immune-related pathways, AML pathways and glucose metabolism pathways were enriched in the high immune cell infiltration cluster. Then we screened the differential immune genes between the two immune cell infiltration clusters. Nine prognostic immune genes were finally identified in the train set by LASSO-Cox regression. We constructed a model in the train set based on the nine prognostic immune genes and validated the predictive capability in the test set. The areas under the ROC curve of the train set and the test set for ROC at 1, 3, 5 years were 0.807, 0.813, 0.815, and 0.731, 0.745, 0.830, respectively. The areas under ROC curve of external validation set in 1, 3, and 5 years were 0.564, 0.619, and 0.614, respectively. People with high risk scores accompanied by high TMB had been detected with the worst prognosis. Single-cell sequencing analysis revealed the expression of prognostic genes in AML cell subsets and pseudo-time analysis described the differentiation trajectory of cell subsets. In conclusion, our results reveal the characteristics of immune microenvironment and cell subsets of AML, while it still needs to be confirmed in larger samples studies. The prognosis model constructed with nine key immune genes can provide a new method to assess the prognosis of AML patients.

Enhancing egg production and quality by the supplementation of probiotic strains (Clostridium and Brevibacillus) via improved amino acid digestibility, intestinal health, immune response, and antioxidant activity.

This study focused on evaluating the influence of Clostridium butyricum and Brevibacillus strains on egg production, egg quality, immune response and antioxidant function, apparent fecal amino acid digestibility, and jejunal morphology when supplemented as probiotics in the diets of laying hens in the peak phase. A total of 288 healthy 30-week-old Hy-Line Brown laying hens were arbitrarily assigned to four dietary groups, which included control diet and control diet supplemented with 0.02% C. butyricum zlc-17, C. butyricum lwc-13, or Brevibacillus zlb-z1, for 84 days. The results showed that dietary C. butyricum and Brevibacillus sp. exerted a positively significant influence (P ≤ 0.05) compared to the control group on the performance, egg quality, and physiological response of the birds. The diets could reduce mortality rate and enhance (P ≤ 0.05) egg weight and egg mass, egg production rate, and feed efficiency. Further analysis suggested that the probiotic strains can enhance (P ≤ 0.05) eggshell quality, Haugh unit, thick albumen content, and albumen height. Also, probiotics enhanced (P ≤ 0.05) the antioxidant status via increased antioxidant enzymes and jejunal morphology as evidenced by increased villi surface area (VSA), the ratio of villi height to crypt depth, villi width, and villi height, and a significant reduction in crypt depth. Besides, nutrient absorption and retention were enhanced, as apparent fecal amino acid digestibility of key essential amino acids was substantially improved in the diet-based group. The concentrations of immunoglobulin M and A (IgM and IgA) increased significantly (P ≤ 0.05) in the probiotics group and the same effect was notable for complement proteins (C3) and immune organ (Spleen). Conclusively, the supplementation of Clostridium butyricum zlc-17 in comparison to Clostridium butyricum lwc-13 and Brevibacillus zlb-z1 strains significantly (P ≤ 0.05) promoted the antioxidant status, modulated the intestinal structure, enhanced amino acid digestibility, and regulated the immunity index of the laying hens, which finally improves the laying performance and egg quality of the laying hens.

Dietary Fructooligosaccharides Effectively Facilitate the Production of High-Quality Eggs via Improving the Physiological Status of Laying Hens.

The focus of this study was to investigate the influence of prebiotics, such as fructooligosaccharides (FOS), on laying performance, egg quality, apparent fecal amino acid digestibility, jejunal morphology, hematological indices, immunological response, and antioxidant capacity in laying hens. A total of 216 healthy Hy-Line Brown laying hens aged 30 weeks were randomly assigned to one of three dietary treatments: basal diet, basal diet supplemented with 0.3 percent FOS, or 0.6 percent FOS. For 84 days, each treatment was fed the corresponding experimental diet. According to the findings, dietary supplementation with FOS enhanced laying performance and egg mass while lowering mortality rate. Albumen height, thick albumen content, Haugh unit, and eggshell thickness were also improved by the prebiotics. Prebiotics also boosted antioxidant status by increasing the activity of antioxidant enzymes, improved morphological development of the jejunum as demonstrated by significant increases in villi height, villi width, ratio of villi height to crypt depth, and reduced crypt depth. The prebiotics group showed a considerable increase in immunoglobulin M, G, and A (IgM, IgG, and IgA) levels, as well as a similar effect on complement proteins (C3). Furthermore, the apparent fecal amino acid digestibility of most essential amino acids was significantly enhanced. Conclusively, fructooligosaccharides at inclusion level of 0.6% efficiently enhanced laying performance and production of high-quality eggs while positively modulating amino acid digestibility, jejunal morphology, antioxidant status, and immune functions of the laying hens.

Comprehensive Analysis of N6-Methyladenosine-Related Long Noncoding RNA Prognosis of Acute Myeloid Leukemia and Immune Cell Infiltration.

N6-Methyladenosine-related long noncoding RNAs play an essential role in many cancers' development. However, the relationship between m6A-related lncRNAs and acute myelogenous leukemia (AML) prognosis remains unclear. We systematically analyzed the association of m6A-related lncRNAs with the prognosis and tumor immune microenvironment (TME) features using the therapeutically applicable research to generate effective treatment (TARGET) database. We screened 315 lncRNAs associated with AML prognosis and identified nine key lncRNAs associated with m6A by the LASSO Cox analysis. A model was established based on these nine lncRNAs and the predictive power was explored in The Cancer Genome Atlas (TCGA) database. The areas under the ROC curve of TARGET and TCGA databases for ROC at 1, 3, and 5 years are 0.701, 0.704, and 0.696, and 0.587, 0.639, and 0.685, respectively. The nomogram and decision curve analysis (DCA) showed that the risk score was more accurate than other clinical indicators in evaluating patients' prognoses. The clusters with a better prognosis enrich the AML pathways and immune-related pathways. We also found a close correlation between prognostic m6A-related lncRNAs and tumor immune cell infiltration. LAG3 expression at the immune checkpoint was lower in the worse prognostic cluster. In conclusion, m6A-related lncRNAs partly affected AML prognosis by remodeling the TME and affecting the anticarcinogenic ability of immune checkpoints, especially LAG3 inhibitors. The prognostic model constructed with nine key m6A-related lncRNAs can provide a method to assess the prognosis of AML patients in both adults and children.

Lithium chloride inhibits infectious bronchitis virus-induced apoptosis and inflammation.

Avian infectious bronchitis (IB) was caused by infectious bronchitis virus (IBV), a coronavirus, which leads to enormous economic losses in the poultry industry. Studies have shown that lithium chloride (LiCl) is a good virus inhibitor. Through cell culture, virus infection, and RT-qPCR, we found that LiCl could down-regulate the apoptosis-related genes Caspase-3 and Bax, up-regulate Bcl-2, and down-regulate the inflammatory-related genes (NF-κB, NLRP3, TNF-α, and IL-1ß) via inhibiting virus replication. Finally, clinical trials showed that LiCl could inhibit IBV-induced apoptosis and inflammatory in chicken embryos as well as reduce the mortality and deformity rate of chicken embryos. The results showed that LiCl has antiviral activity against IBV and clinical effects. Further studies are required to explore the exact action mechanism of LiCl on IBV-induced apoptosis and inflammation.

Invasive Pathobionts Contribute to Colon Cancer Initiation by Counterbalancing Epithelial Antimicrobial Responses.

BACKGROUND & AIMS: Microbiota dysbiosis and mucosa-associated bacteria are involved in colorectal cancer progression. We hypothesize that an interaction between virulent pathobionts and epithelial defense promotes tumorigenesis. METHODS: Chemical-induced CRC mouse model was treated with antibiotics at various phases. Colonic tissues and fecal samples were collected in a time-serial mode and analyzed by gene microarray and 16S rRNA sequencing. Intraepithelial bacteria were isolated using a gentamicin resistance assay, and challenged in epithelial cultures. RESULTS: Our study showed that antibiotic treatment at midphase but not early or late phase reduced mouse tumor burden, suggesting a time-specific host-microbe interplay. A unique antimicrobial transcriptome profile showing an inverse relationship between autophagy and oxidative stress genes was correlated with a transient surge in microbial diversity and virulence emergence in mouse stool during cancer initiation. Gavage with fimA/fimH/htrA-expressing invasive Escherichia coli isolated from colonocytes increased tumor burden in recipient mice, whereas inoculation of bacteria deleted of htrA or triple genes did not. The invasive E.coli suppressed epithelial autophagy activity through reduction of microtubule-associated protein 1 light-chain 3 transcripts and caused dual oxidase 2-dependent free radical overproduction and tumor cell hyperproliferation. A novel alternating spheroid culture model was developed for sequential bacterial challenge to address the long-term changes in host-microbe interaction for chronic tumor growth. Epithelial cells with single bacterial encounter showed a reduction in transcript levels of autophagy genes while those sequentially challenged with invasive E.coli showed heightened autophagy gene expression to eliminate intracellular microbes, implicating that bacteria-dependent cell hyperproliferation could be terminated at late phases. Finally, the presence of bacterial htrA and altered antimicrobial gene expression were observed in human colorectal cancer specimens. CONCLUSIONS: Invasive pathobionts contribute to cancer initiation during a key time frame by counterbalancing autophagy and oxidative stress in the colonic epithelium. Monitoring gut microbiota and antimicrobial patterns may help identify the window of opportunity for intervention with bacterium-targeted precision medicine.

Crocetin Alleviates Ovariectomy-Induced Metabolic Dysfunction through Regulating Estrogen Receptor ß.

Metabolic dysfunction (MD) is a major health problem threatening the life quality of menopausal women. Saffron has been widely used in herb prescriptions for treating menopausal syndrome. However, the pharmacological effects and mechanisms of saffron are poorly understood. Here, we investigated the effect of crocin, the major ingredient of saffron and its active metabolite in blood, crocetin, on MD and lipid metabolism in ovariectomized (OVX) mice and 3T3-L1 adipocytes. The present study showed that intragastric treatment of crocin prevented weight gain, fat accumulation, and insulin resistance in OVX mice by increasing energy expenditure and fat oxidation. Mechanistically, crocin influenced adipose tissue homeostasis by regulating adipogenic and lipolytic factors, which was strongly associated with the restoration of the downregulated ERß function in white adipose tissue (WAT). In vitro, crocetin facilitated lipid metabolism in an ERß-dependent manner. Our results demonstrated the beneficial effects of crocetin/crocin-mediated intervention against metabolic dysfunction, revealing a prospective therapeutic application in menopausal women.

Better Medications Adherence Lowers Cardiovascular Events, Stroke, and All-Cause Mortality Risk: A Dose-Response Meta-Analysis.

AIMS: We investigated the association between vascular medication adherence, assessed by different methods, and the risk of cardio-cerebrovascular events and all-cause mortality. METHODS: A meta-analysis with a systematic search of PubMed, Web of Science, EMBASE, and Cochrane databases from inception date to 21 June 2021 was used to identify relevant studies that had evaluated the association between cardiovascular medication adherence levels and cardiovascular events (CVEs), stroke, and all-cause mortality risks. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects meta-analysis. Restricted cubic splines were used to model the dose-response association. RESULTS: We identified 46 articles in the dose-response meta-analysis. The dose-response analysis indicated that a 20% increment in cardiovascular medication, antihypertensive medication, and lipid-lowering medication adherence level were associated with 9% (RR: 0.91, 95% CI 0.88-0.94), 7% (RR 0.93, 95% CI: 0.84-1.03), and 10% (RR 0.90, 95% CI: 0.88-0.92) lowers risk of CVEs, respectively. The reduced risk of stroke respectively was 16% (RR: 0.84, 95% CI: 0.81-0.87), 17% (RR 0.83, 95% CI: 0.78-0.89), and 13% (RR 0.87, 95% CI: 0.84-0.91). The reduced risk of all-cause mortality respectively was 10% (RR: 0.90, 95% CI: 0.87-0.92), 12% (RR 0.88, 95% CI: 0.82-0.94), and 9% (RR 0.91, 95% CI: 0.89-0.94). CONCLUSIONS: A better medication adherence level was associated with a reduced risk of cardio-cerebrovascular events and all-cause mortality.

Bi-phasic effect of gelatin in myogenesis and skeletal muscle regeneration.

Skeletal muscle regeneration requires extracellular matrix (ECM) remodeling, including an acute and transient breakdown of collagen that produces gelatin. Although the physiological function of this process is unclear, it has inspired the application of gelatin to injured skeletal muscle for a potential pro-regenerative effect. Here, we investigated a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by the hormetic effects of reactive oxygen species (ROS). Low-dose gelatin stimulated ROS production from NADPH oxidase 2 (NOX2) and simultaneously upregulated the antioxidant system for cellular defense, reminiscent of the adaptive compensatory process during mild stress. This response triggered the release of the myokine IL-6, which stimulates myogenesis and facilitates muscle regeneration. By contrast, high-dose gelatin stimulated ROS overproduction from NOX2 and the mitochondrial chain complex, and ROS accumulation by suppressing the antioxidant system, triggering the release of TNFα, which inhibits myogenesis and regeneration. Our results have revealed a bi-phasic role of gelatin in regulating skeletal muscle repair mediated by intracellular ROS, the antioxidant system and cytokine (IL-6 and TNFα) signaling.

The Evaluation of UPro as a New Nutrient on High-Quality Egg Production From the Perspective of Egg Properties, Intestinal Histomorphology, and Oviduct Function of Laying Hens.

This study was to investigate the effects of UPro as a new nutritive fortifier on high-quality egg production from the perspective of egg properties, intestinal histomorphology, and oviduct function of laying hens. Four hundred thirty-two Hy-Line Brown laying hens aged 56 weeks were allocated to four groups. Layers were given a basal diet or supplemented with different levels of small peptides (0.2, 0.4, and 0.8%) to replace soybean meal. After 1-week adaptation period, the feeding trial was conducted for 12 weeks. The results showed that UPro addition significantly decreased (P < 0.05) the hardness, stickiness, and chewiness of albumen of layers on weeks 12. A linear elevation (P < 0.05) in the albumen height, Haugh unit (HU), and crude protein content of albumen of layers were noted on week 12 along with dietary UPro addition increasing, and the villus height (VH) and villus height-to-crypt depth radio (VCR) of jejunum also linearly increasing (P < 0.05). In addition, there were linear elevations (P < 0.05) in the relative mRNA expression of Sec23 homolog A (Sec23A) and protein-O-mannosyltransferase1 (POMT1) in layers as dietary UPro addition increased. In conclusion, dietary UPro addition could improve intestinal health, increase the absorption of nutrients, and improve egg quality of laying hens. The possible mechanism underlying UPro improving the quality and processing characteristics of albumen is up-regulating Sec23A and POMT1 expression of magnum. These findings will promote the application of UPro as a new nutritional additive in the production of high-quality eggs.