Development of small intestinal barrier function and underlying mechanism in Chinese indigenous and Duroc piglets during suckling and weaning periods.

This study explored the developmental changes in small intestinal barrier function and the potential regulatory roles of intestinal microbiota and metabolites in different breeds of piglets during suckling and weaning periods. Taoyuan black (TB), Xiangcun black (XB), and Duroc (DR) piglets (10 litters per breed; half male and half female) were selected for sampling to evaluate the intestinal barrier-related indexes and intestinal microbiota and metabolites at 1, 10, 21 (weaned), and 24 (3 d after weaning) d old. The results showed that weaning led to severe shedding of small intestinal microvilli and sparse microvilli arrangement. D-lactate level in the ileum of TB and XB piglets during suckling and weaning periods was lower (P < 0.01) than that of DR piglets, as well as the ileal diamine oxidase level at 1 d old. The expression level of mucin 1 was higher (P < 0.05) in the ileum of TB and XB piglets than that of DR piglets, and it was the highest in the ileum of TB piglets at 21 d old. The expression levels of mucin 2 and mucin 13 were higher (P < 0.10) in TB and XB piglets than those of DR piglets at 21 d old, whereas mucin 2 and mucin 13 in the ileum of TB and XB piglets were higher (P < 0.05) than those of DR piglets at 24 d old. TB and XB piglets had a lower relative abundance of Escherichia_Shigella at 21 and 24 d old, but they had higher Streptococcus at 1 and 24 d old than DR piglets (P < 0.01). Differential metabolites between the three breeds of piglets were mainly related to oxidative phosphorylation, steroid biosynthesis, and bile acid synthesis. Collectively, these findings suggest that different pig breeds present differences in the development of the small intestinal barrier function. Compared with DR piglets, TB and XB piglets had higher intestinal permeability during the suckling period and a stronger intestinal mechanical barrier after weaning. Moreover, intestinal microbiota and metabolites are the key factors for developing small intestinal barrier functions in different breeds of piglets.

Autophagy inhibition mediated by trillin promotes apoptosis in hepatocellular carcinoma cells via activation of mTOR/STAT3 signaling.

Apoptosis and autophagy have been shown to act cooperatively and antagonistically in self-elimination process. On the one side, apoptosis and autophagy can act as partners to induce cell death in a coordinated or cooperative manner; on the flip side, autophagy acts as an antagonist to block apoptotic cell death by promoting cell survival. Our previous research indicated that trillin could induce apoptosis of PLC/PRF/5 cells, but the effects of trillin on autophagy as well as its functional relationship to apoptosis have not been elucidated. Here, the running study aims to investigate the function and molecular mechanism of trillin on autophagy with hepatocellular carcinoma (HCC) cells. The objective of this study is to investigate the molecular mechanism of trillin on autophagy in HCC cells. Protein levels of autophagy markers beclin1, LC3B, and p62 were detected by western blotting. 6-Hydroxyflavone and stattic were used to test the role of trillin regulation of autophagy via serine threonine kinase (AKT)/extracellular-regulated protein kinases (ERK) 1/2/mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Flow cytometry was used to detect caspase 3 activity and apoptosis in PLC/PRF/5 cells treated with trillin for 24 h with or without rapamycin, stattic, and 6-hydroxyflavone. The protein level of autophagy marker beclin1 was decreased, whilst the protein level of p62 was significantly increased by trillin treatment, indicating trillin treatment led to inhibition of autophagy in HCC cells. Trillin treatment could reduce the protein levels of p-AKT and p-ERK1/2, but enhance the protein levels of mTOR and p-mTOR, suggesting that trillin could inhibit AKT/ERK rather than mTOR. The AKT/ERK activator 6-hydroxyflavone could reverse the loss of AKT and ERK1/2 phosphorylation induced by trillin, implying that trillin impairs autophagy through activated mTOR rather than AKT/ERK. STAT3 and p-STAT3 were significantly upregulated by the trillin treatment with an increase in dose from 0 to 50 µM, suggesting that autophagy inhibition is mediated by trillin via activation of STAT3 signaling. The STAT3 inhibitor stattic significantly reversed the increased STAT3 phosphorylation at tyrosine 705 induced by trillin. The mTOR signaling inhibitor rapamycin reversed the trillin-induced mTOR phosphorylation enhancement but exerted no effects on total mTOR levels, suggesting trillin treatment led to inhibition of autophagy in HCC cells through activating mTOR/STAT3 pathway. Furthermore, caspase 3 activities and the total rate of apoptosis were increased by trillin treatment, which was reversed by rapamycin, stattic, and 6-hydroxyflavone, proving that trillin promotes apoptosis via activation of mTOR/STAT3 signaling. Trillin induced autophagy inhibition and promoted apoptosis in PLC/PRF/5 cells via the activation of mTOR/STAT3 signaling. Trillin has the potential to be a viable therapeutic option for HCC treatment.

Expressions of Insulin-like Growth Factor System among Different Breeds Impact Piglets' Growth during Weaning.

The present study investigated the insulin-like growth factors (IGFs) and their receptors and binding proteins among three pig breeds during weaning. Sixty Duroc (DR), Taoyuan black (TYB), and Xiangcun black (XCB) piglets (20 piglets per breed) were selected at 21 and 24 (3 days of post-weaning) days of age to analyze organ indices, plasma concentrations of IGF and IGF-binding proteins (IGFBPs) using ELISA kits, and gene expression of IGF-system-related components in different tissues. The plasma IGFBP-3 concentration in TYB piglets was higher (p > 0.05) than in the XCB and DR piglets at 21 days of age. At 21 days of age, compared with the DR piglets, the IGF-1 expression was lower (p < 0.05) in the kidney, but it was higher (p < 0.05) in the spleen of XCB and TYB piglets. At 24 days of age, the IGF-1 expression was higher (p < 0.05) in the kidney of TYB piglets than in the XCB and DR piglets, while IGFBP-3 in the stomach and IGFBP-4 in the liver of XCB and TYB piglets were lower (p < 0.05) compared with the DR piglets. Weaning down-regulated (p < 0.05) IGF-1 expression in the jejunum, spleen, and liver of piglets, while it up-regulated (p < 0.05) IGFBP-3 expression in the stomach, IGFBP-4 in the liver, IGFBP-5 in the ileum, and IGFBP-6 in the jejunum of DR piglets. Spearman's correlation analysis showed a negative correlation (p < 0.05) between plasma IGFBP-2 and IGFBP-5 concentration and the organ indices of piglets. Collectively, there were significant differences in the IGF system components among the three pig breeds. The IGF system components were altered during weaning, which might be involved in weaning stress to decrease the growth of piglets.

Transcriptional characteristics and functional validation of three monocyte subsets during aging.

BACKGROUND: Age-associated changes in immunity are inextricably linked to chronic inflammation and age-related diseases, the impact of aging on monocyte subsets is poorly understood. METHODS: Flow cytometry was applied to distinguish three monocyte subsets between 120 young and 103 aged individuals. We then analyzed the expression profiles of three monocyte subsets from 9 young and 9 older donors and CD14+ monocytes from 1202 individuals between 44 and 83 years old. Flow cytometry was used to measure ß-galactosidase activities, ROS levels, mitochondrial contents, mitochondrial membrane potentials (MMPs) and intracellular IL-6 levels in three monocyte subsets of young and elderly individuals, and plasma IL-6 levels were detected by electrochemiluminescence immunoassay. Mitochondrial stress and glycolytic rate of CD14+ monocytes from young and aged individuals were measured by Seahorse XFe24 Analyzer. RESULTS: Compared with young individuals, the percentage of classical subset in aged persons significantly decreased, while the proportion of nonclassical subset increased. Age-related differential genes were obviously enriched in cellular senescence, ROS, oxidative phosphorylation, mitochondrial respiratory chain, IL-6 and ribosome-related pathways. Compared with young individuals, the ß-galactosidase activities, ROS contents, intracellular IL-6 levels of three monocyte subsets, and plasma IL-6 levels in aged individuals were significantly elevated, while the MMPs apparently declined with age and the mitochondrial contents were only increased in intermediate and nonclassical subsets. CD14+ monocytes from elderly adults had conspicuously lower basal and spare respiratory capacity and higher basal glycolysis than those from young individuals. CONCLUSIONS: During aging, monocytes exhibited senescence-associated secretory phenotype, mitochondrial dysfunction, decreased oxidative phosphorylation and increased glycolysis and the nonclassical subset displayed the clearest features of aging. Our study comprehensively investigated age-related transcriptional alterations of three monocyte subsets and identified the pivotal pathways of monocyte senescence, which may have significant implications for tactics to alleviate age-related conditions.

Correction: Muscle characteristics comparison and targeted metabolome analysis reveal differences in carcass traits and meat quality of three pig breeds.

Correction for 'Muscle characteristics comparison and targeted metabolome analysis reveal differences in carcass traits and meat quality of three pig breeds' by Bo Song et al., Food Funct., 2023, 14, 7603-7614, https://doi.org/10.1039/D2FO03709B.

Muscle characteristics comparison and targeted metabolome analysis reveal differences in carcass traits and meat quality of three pig breeds.

This study investigated the molecular basis for differences in meat yield and quality between Duroc, Taoyuan black (TB), and Xiangcun black (XB) pigs. The results show that TB pigs have lower carcass weight, lean percentage, pH decline, and glycolytic potential but have higher fat percentage, water- holding capacity, intramuscular fat content, antioxidant capacity, and percentage of slow-twitch fibers than the Duroc pigs. Moreover, muscles of TB pigs have lower protein synthesis and lipolysis gene expression than the muscles of Duroc pigs. Targeted metabolome analysis indicates that 24 metabolites significantly differ among these three pig breeds. Correlation analysis suggests that L-malic acid and ß-alanine contents in muscle are closely related to meat quality. These findings suggest that the excellent meat quality of TB pigs is closely related to muscle metabolism and fiber characteristics, while lower protein synthesis and lipolysis may contribute to less meat yield.

Sodium butyrate alleviates deoxynivalenol-induced porcine intestinal barrier disruption by promoting mitochondrial homeostasis via PCK2 signaling.

Deoxynivalenol (DON) is one of the most plentiful trichothecenes occurring in food and feed, which brings severe health hazards to both animals and humans. This study aims to investigate whether sodium butyrate (NaB) can protect the porcine intestinal barrier from DON exposure through promoting mitochondrial homeostasis. In a 4-week feeding experiment, 28 male piglets were allocated according to a 2 by 2 factorial arrangement of treatments with the main factors including supplementation of DON (< 0.8 vs. 4.0 mg/kg) and NaB (0.0 vs. 2 g/kg) in a corn/soybean-based diet. Dietary NaB supplementation mitigated the damaged mitochondrial morphology within the jejunal mucosa and the disrupted gut epithelial tight junctions irritated by DON. In IPEC-J2 cells, we found efficient recovery of the intestinal epithelial barrier occurred following NaB administration. This intestinal barrier reparation was facilitated by NaB-induced PCK2-mediated glyceroneogenesis and restoration of mitochondrial structure and function. In conclusion, we elucidated a mechanism of PCK2-mediated improvement of mitochondrial function by NaB to repair porcine intestinal barrier disruption during chronic DON exposure. Our findings highlight the promise of NaB for use in protecting against DON-induced gut epithelial tight junction disruption in piglets.

Metabolomics Analysis Reveals the Potential Relationship Between Sow Colostrum and Neonatal Serum Metabolites in Different Pig Breeds.

SCOPE: Colostrum composition is an important indicator of newborn piglet survival and growth. However, limited information is available on the association between colostrum metabolites in sows and serum metabolites in neonates. Therefore, the present study aims to determine the metabolites in the colostrum of sows, in the serum of their offspring piglets, and mother-offspring metabolite correlations in different pig breeds. METHODS AND RESULTS: Colostrum and serum samples are collected from 30 sows and their piglets from three pig breeds (Taoyuan black, TB; Xiangcun black, XB; and Duroc) to analyze the targeted metabolomics. This study identifies 191 metabolites in the colostrum of sows, including fatty acids, amino acids, bile acids, carnitines, carbohydrates, and organic acids, and the concentrations of these metabolites are highest in the TB pigs. Metabolite profiles in sow colostrum and piglet serum differ among Duroc, TB, and XB pigs, and the matching metabolites are mainly enriched in the digestive system and transportation pathways. Furthermore, identification of the associations between metabolites in the colostrum of sows and their neonate sera suggests that metabolite compounds from colostrum are transported to suckling piglets. CONCLUSION: The present study findings deepen the understanding of the composition of sow colostrum metabolites and the transportation of metabolites from sow colostrum to piglets. The findings also provide insight regarding the development of dietary formulas that resemble the sow colostrum for newborn animals to maintain health and improve the early growth of offspring.

[Analysis of a child with X-linked intellectual disability due to a maternal de novo splicing variant of the PAK3 gene].

OBJECTIVE: To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities. METHODS: A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay. RESULTS: WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3). CONCLUSION: The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.

Small Intestinal Digestive Functions and Feed Efficiency Differ in Different Pig Breeds.

Small intestinal growth and health affect its digestion and absorption ability, while little information exists about the small intestinal morphology and function differences among the different pig breeds. Therefore, 90 healthy 35 days of age Taoyuan black (TB), Xiangcun black (XB), and Duroc (DR) pigs (30 pigs per breed) with similar body weight (BW) of the same breed were reared to 185 days of age to evaluate the potential relationship between feed efficiency and small intestinal morphology and function at 80, 125, and 185 days of age. The results show that the TB and XB pigs had lower initial and final BW, ADG, and ADFI and plasma CHO and LDL-C levels, whereas they had higher plasma LIP levels and jejunal trypsin, invertase, lactase, and maltase activities and higher DM, ADF, Tyr, Arg, and His digestibility at 80 days of age compared with the DR pigs. At 125 days of age, TB and XB pigs had lower apparent total tract digestibility and plasma CHO, HDL-C, LDL-C, and NH3 levels; XB pigs had lower DM and NDF digestibility, and TB pigs had higher jejunal lactase and maltase activities. At 185 days of age, TB and XB pigs had lower DM, EE, ADF, and GE digestibility, while having higher plasma ALT and UN levels; TB pigs had higher plasma AST level and jejunal chymase activity. Furthermore, the plasma free amino acid contents, small intestinal VH, and nutrient transporter expression levels differed at different ages. Therefore, the different pig breeds exhibited significantly different growth performance and small intestinal growth, mainly resulting from the differences in digestive enzymes and nutrient transporters in the small intestine.

Sow-Offspring Diets Supplemented with Probiotics and Synbiotics Are Associated with Offspring's Growth Performance and Meat Quality.

Probiotics and synbiotics supplementation have been shown to play potential roles in animal production. The present study aimed to evaluate the effects of dietary probiotics and synbiotics supplementation to sows during gestation and lactation and to offspring pigs (sow-offspring) on offspring pigs' growth performance and meat quality. Sixty-four healthy Bama mini-pigs were selected and randomly allocated into four groups after mating: the control, antibiotics, probiotics, and synbiotics groups. After weaning, two offspring pigs per litter were selected, and four offspring pigs from two litters were merged into one pen. The offspring pigs were fed a basal diet and the same feed additive according to their corresponding sows, representing the control group (Con group), sow-offspring antibiotics group (S-OA group), sow-offspring probiotics group (S-OP group), and sow-offspring synbiotics group (S-OS group). Eight pigs per group were euthanized and sampled at 65, 95, and 125 d old for further analyses. Our findings showed that probiotics supplementation in sow-offspring diets promoted growth and feed intake of offspring pigs during 95-125 d old. Moreover, sow-offspring diets supplemented with probiotics and synbiotics altered meat quality (meat color, pH45min, pH24h, drip loss, cooking yield, and shear force), plasma UN and AMM levels, and gene expressions associated with muscle-fiber types (MyHCI, MyHCIIa, MyHCIIx, and MyHCIIb) and muscle growth and development (Myf5, Myf6, MyoD, and MyoG). This study provides a theoretical basis for the maternal-offspring integration regulation of meat quality by dietary probiotics and synbiotics supplementation.

Dietary fiber alters immunity and intestinal barrier function of different breeds of growing pigs.

Introduction: Dietary fiber (DF) regulates immune response and barrier function by interacting with epithelial cells and immune cells. However, the differences in the regulation of intestinal health of different pig breeds by DF remain obscure. Methods: A total of 60 healthy pigs (20 pigs/breed) from Taoyuan black (TB), Xiangcun black (XB), and Duroc (DR) pigs (body weight = 11.00 ± 1.00 kg) were fed two different levels (low and high) of DF for 28 days to evaluate the differences in the modulation of intestinal immunity and barrier function by DF in different pig breeds. Results: TB and XB pigs had higher plasma Eos level, Eos%, and Lym% but lower Neu level compared with the DR pigs when fed low DF (LDF). The TB and XB pigs had higher plasma Eos, MCV, and MCH levels and Eos% while lower Neu% compared with the DR pigs when fed high DF (HDF). HDF decreased IgA, IgG, IgM, and sIgA concentrations in the ileum of TB and XB pigs compared with the DR pigs, while the plasma IgG and IgM concentrations of TB pigs were higher than those of the DR pigs. Moreover, compared with the DR pigs, HDF decreased the levels of IL-1ß, IL-17, and TGF-ß in the plasma, and IL-1ß, IL-2, IL-6, IL-10, IL-17, IFN-γ, TGF-ß, and TNF-α in the ileum of TB and XB pigs. However, HDF did not affect the mRNA expression of cytokines in the ileum of TB, XB, and DR pigs, while HDF increased the TRAF6 expression of TB pigs compared with the DR pigs. In addition, HDF increased the Claudin abundance of TB and DR pigs compared with the pigs feeding with LDF. Moreover, in the LDF and HDF groups, the XB pigs had higher protein abundances of Claudin and ZO-1 compared with the TB and DR pigs. Conclusions: DF regulated the TB and DR pigs' plasma immune cells, the XB pigs showed enhanced barrier function, and the DR pigs had increased ileal inflammation, which indicates that Chinese indigenous pigs are more DF tolerant than the DR pigs.

Expanding individualized therapeutic options via genoproteomics.

Clinical next-generation sequencing (NGS) tests have enabled treatment recommendations for cancer patients with driver gene mutations. Targeted therapy options for patients without driver gene mutations are currently unavailable. Herein, we performed NGS and proteomics tests on 169 formalin-fixed paraffin-embedded (FFPE) samples of non-small cell lung cancers (NSCLC, 65), colorectal cancers (CRC, 61), thyroid carcinomas (THCA, 14), gastric cancers (GC, 2), gastrointestinal stromal tumors (GIST, 11), and malignant melanomas (MM, 6). Of the 169 samples, NGS detected 14 actionable mutated genes in 73 samples, providing treatment options for 43% of the patients. Proteomics identified 61 actionable clinical drug targets approved by the FDA or undergoing clinical trials in 122 samples, providing treatment options for 72% of the patients. In vivo experiments demonstrated that the Mitogen-Activated Protein Kinase (MEK) inhibitor could block lung tumor growth in mice with overexpression of Map2k1 protein. Therefore, protein overexpression is a potentially feasible indicator for guiding targeted therapies. Collectively, our analysis suggests that combining NGS and proteomics (genoproteomics) could expand the targeted treatment options to 85% of cancer patients.

Epigenetic and epitranscriptomic regulation of axon regeneration.

Effective axonal regeneration in the adult mammalian nervous system requires coordination of elevated intrinsic growth capacity and decreased responses to the inhibitory environment. Intrinsic regenerative capacity largely depends on the gene regulatory network and protein translation machinery. A failure to activate these pathways upon injury is underlying a lack of robust axon regeneration in the mature mammalian central nervous system. Epigenetics and epitranscriptomics are key regulatory mechanisms that shape gene expression and protein translation. Here, we provide an overview of different types of modifications on DNA, histones, and RNA, underpinning the regenerative competence of axons in the mature mammalian peripheral and central nervous systems. We highlight other non-neuronal cells and their epigenetic changes in determining the microenvironment for tissue repair and axon regeneration. We also address advancements of single-cell technology in charting transcriptomic and epigenetic landscapes that may further facilitate the mechanistic understanding of differential regenerative capacity in neuronal subtypes. Finally, as epigenetic and epitranscriptomic processes are commonly affected by brain injuries and psychiatric disorders, understanding their alterations upon brain injury would provide unprecedented mechanistic insights into etiology of injury-associated-psychiatric disorders and facilitate the development of therapeutic interventions to restore brain function.

Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3ß Pathway.

OBJECTIVE: To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin. METHODS: Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively. RESULTS: Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3ß (GSK3ß), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05). CONCLUSION: Baicalin can promote the development of hippocampal neurons via mTOR/GSK3ß signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

Comparison of the Pig Breeds in the Small Intestinal Morphology and Digestive Functions at Different Ages.

The small intestine is the main site for digestion and absorption of nutrients, and the development of the small intestine can be affected by several factors, such as diet composition, age, and genotype. Thus, this study aimed to compare the small intestinal morphology and digestive function differences at different ages of three pig breeds. Thirty litters of newborn Taoyuan black (TB), Xiangcun black (XB), and Duroc (DR) piglets (ten litters per breed) were selected for this study. Ten piglets from each breed were selected and sampled at 1, 10, 21, and 24 days old. The results showed that the TB and XB piglets had lower growth but had higher lactase and maltase activities in the jejunum compared with the DR piglets, while most of the digestive enzyme activities in the ileum were higher in the DR piglets at different ages. The expression levels of nutrient transporters, mainly including amino acids, glucose, and fatty acids transporters, differed in the jejunum at different ages among three pig breeds and were higher in the DR piglets at 1 day old and XB piglets at 24 days old. Collectively, these findings suggest that the phenotypic differences in the growth, intestinal morphology, and digestive function among the three pig breeds mainly resulted from the differences in digestive enzymes and nutrient transporters in the intestine.

Comparing Predictability of Non-invasive Tools for Hepatocellular Carcinoma in Treated Chronic Hepatitis C Patients.

BACKGROUND: Non-invasive tools including liver stiffness measurement (LSM) or FIB-4, assessed before or after direct acting antivirals (DAA), have been suggested to predict hepatocellular carcinoma (HCC). AIMS: This study aims to compare predictability of HCC by these methods at different time points, to validate the HCC surveillance suggestion by guidelines, and to propose personalized strategy. METHODS: Chronic hepatitis C whose LSM and FIB-4 were available at pretherapy and after sustained virological response (SVR) were enrolled. Advanced chronic liver disease (ACLD) was defined as pretherapy LSM ≥ 10 kPa or FIB-4 index ≥ 3.25 or ultrasound signs of cirrhosis plus platelet count < 150,000/µL. The predictabilities were compared by area under ROC. The cumulative HCC incidences were calculated by Kaplan-Meier analysis. RESULTS: Among 466 ACLD patients, 40 patients developed HCC during a follow-up duration of 26.8 months. Comparable predictive performances for HCC between LSM and FIB-4 at pretherapy and SVR were noted. By guidelines suggestion using pretherapy LSM = 10 kPa (advanced fibrosis) and 13 kPa (cirrhosis) for risk stratification, the annual HCC incidences of those with LSM of < 10, 10-12.9 and ≥ 13 kPa were 1.1, 3.6, and 5.0%, respectively. Combination of baseline LSM < 12 kPa and SVR FIB-4 < 3.7 could further stratify relatively low risk of HCC in ACLD patients of annal incidence of 1.2%. CONCLUSIONS: ACLD patients who met advanced fibrosis but not cirrhosis by guidelines' cut-offs still posed high risk of HCC. Baseline LSM with SVR FIB-4 can be applied to stratify low, intermediate, and high risk of HCC for personalizing surveillance strategies after SVR.

Identification of a new benzophenanthridine alkaloid from Eomecon chionantha induced necroptosis in breast cancer cells.

Benzophenanthridine alkaloids of secondary metabolites from Chinese herb medicine are the excellent anticancer agent to fight sensitive and resistant breast cancer, which is one of the major malignant tumors in females. In the present study, a new benzophenanthridine alkaloid derivatives 8,12-dimethoxysanguinarine (1, SG-A) was isolated from Eomecon chionantha. And MCF-7 cell lines were strongly inhibited by SG-A with an IC50 value of 7.45 µΜ. Furthermore, SG-A strikingly induced non-apoptotic cell death via necroptosis in MCF-7 cells through flow cytometry, Hoechest 33258 and TEM cell morphology analysis. The results suggested that SG-A was found to induce cell necroptosis in MCF-7 cells.

Developmental Changes of Immunity and Different Responses to Weaning Stress of Chinese Indigenous Piglets and Duroc Piglets during Suckling and Weaning Periods.

To investigate developmental changes in immunity and different responses to weaning stress of piglets from different breeds during suckling and weaning periods, a total of 30 litters of Taoyuan black (TB) piglets, Xiangcun black (XB) piglets, and Duroc (DR) piglets (ten litters per breed) were selected at 1, 10, 21, and 24 days of age, respectively. The results showed that the liver index of TB piglets was higher at 10 days of age than that of the other days of age and breeds. Regardless of the days of age, TB and XB piglets had a higher plasma IgA level and lower ileal IgM level than in the DR piglets, and XB piglets had a lower plasma IgG level than the other breeds. TB and XB piglets had a higher IL-6 level and lower IL-17 level in plasma at 24 days of age than DR piglets, regardless of the days of age. The ileal levels of IL-2, IL-10, IFN-γ, and TNF-α were lower in the TB and XB piglets at 24 days of age than in the DR piglets. The ileal expression levels of IRAK1, CD14, MyD88, and NF-κB were down-regulated in the TB and XB piglets at 24 days of age compared to those in the DR piglets. These findings suggest that there were differences in the development of immune function among different pig breeds. Moreover, TB and XB piglets presented stronger resistance to weaning stress than the DR piglets, which may be related to the immune regulation mediated by the MyD88/NF-κB signaling pathway.