Patterns of alteration in boar semen quality from 9 to 37 months old and improvement by protocatechuic acid.

BACKGROUND: Comprehending the patterns of alteration in boar semen quality and identifying effective nutritional interventions are crucial for enhancing the productivity of commercial pig systems. This study aimed to examine the alteration in semen quality in boars, and assess the impact of protocatechuic acid (PCA) on semen quality during the phase of declining semen quality. METHODS: In Exp. 1, a total of 38 Pig Improvement Company (PIC) boars were selected and their semen quality data were recorded from the age of 9 to 37 months. In Exp. 2, 18 PIC boars (28 months old) were randomly assigned into three groups (n = 6) and fed a basal diet, a basal diet containing 500 or 1,000 mg/kg PCA, respectively. The experiment lasted for 12 weeks. RESULTS: The semen volume, concentration, and total number of spermatozoa in boars exhibited an increase from 9 to 19 months old and showed a significant linear decreased trend in 28, 24, and 22 months old. Sperm motility displayed an upward trajectory, reaching its peak at 20 months of age, and showed a significant linear decreased trend at 20 months old. Dietary supplementation of PCA demonstrated an effect to mitigate the decrease in semen volume, concentration of spermatozoa, total number of spermatozoa (P > 0.05), and significantly increased the sperm motility (P < 0.05). Moreover, supplementation of 1,000 mg/kg PCA significantly increased the sperm viability (P < 0.05). Analysis on cellular signaling pathways revealed that PCA restored serum testosterone levels and alleviated oxidative damage by upregulating the expression of HO-1, SOD2, and NQO1 in testicular stromal cells. Notably, PCA can enhance phosphorylation by selectively binding to AMP-activated protein kinase (AMPK) protein, thereby improving sperm mitochondrial function and augmenting sperm motility via PGC-1/Nrf1. CONCLUSIONS: These data elucidated the pattern of semen quality variation in boars within the age range of 9 to 37 months old, and PCA has the potential to be a natural antioxidant to enhance sperm quality through modulation of the AMPK/PGC-1/Nrf1 signaling pathway.

Effects of Prevotella copri on insulin, gut microbiota and bile acids.

Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between Prevotella copri (P. copri) and obesity in children (p = 0.003). Next, the effect of P. copri on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of P. copri. increased serum levels of fasting blood glucose (p < 0.01), insulin (p < 0.01) and interleukin-1ß (IL-1ß) (p < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that P. copri reduced the relative abundance of the Akkermansia genus in mice (p < 0.01). Further analysis on bile acids (BAs) revealed that P. copri increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice (p < 0.05). This study demonstrated for the first time that P. copri has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of Akkermansia genus and bile acids.

The role of uterus mitochondrial function in high-fat diet-related adverse pregnancy outcomes and protection by resveratrol.

This study elucidates the mechanism of obesity-related adverse pregnancy outcomes and further investigates the effect of resveratrol on reproductive performance in a short- or long-term HFD-induced obese mouse model. Results show that maternal weight had a significant positive correlation with litter mortality in mice. A long-term HFD increased body weight and litter mortality with decreased expression of uterine cytochrome oxidase 4 (COX4), which was recovered by resveratrol in mice. Moreover, HFD decreased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factors-1 (Nrf-1), and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) and increased the expression of phosphorylated extracellular regulated protein kinases (p-ERK) in the uterus. Resveratrol, a polyphenol that can directly bind to the ERK protein, suppressed the phosphorylation of ERK, increased the expression of p-AMPK, PGC-1α and Nrf-1, and decreased litter mortality in mice.

Effects of main active components of rosemary on growth performance, meat quality and lipid metabolism in finishing pigs.

Rosemary extracts have been widely used as feed additives in recent years. This study aimed to investigate the effects of rosmarinic acid (RA) and ursolic acid (UA), the main active components of rosemary, on growth performance, meat quality and lipid metabolism in finishing pigs. A total of 72 finishing pigs (Landrace; initial age of 150 d) were randomly divided into 3 treatments with 8 replicates of 3 pigs each, and fed a basal diet or diet containing 500 mg/kg of RA or UA. The results showed that dietary supplementation of RA or UA had no significant effect on the growth performance and carcass traits of finishing pigs (P > 0.05). However, both RA and UA significantly increased the triglyceride (TG) level in soleus muscle (P < 0.001). Supplementation of RA increased the expression of genes related to lipogenesis and transport including fatty acid synthase (FAS) (P < 0.001), sterol regulatory element binding protein-1c (SREBP1c) (P < 0.001) and peroxisome proliferator-activated receptor γ (PPARγ) (P < 0.05), while UA increased the expression of fatty acid transport protein 1 (FATP1), a gene related to lipid uptake (P < 0.05). However, RA reduced the expression of adipogenesis-related gene acetyl-coenzyme A carboxylase α (ACCα) (P < 0.01). Characterization of cecal microbiota indicated that RA increased the microbial richness (chao 1, P < 0.001) and diversity (observed species, P < 0.01). Further analysis of the genera revealed that RA increased the relative abundance of Bacteroides and g-UCG-005 (P < 0.05), and UA enriched Prevotella (P < 0.001). Correlation analysis showed that g-UCG-005 was positively correlated with the expression of FAS, carnitine palmitoyl transferase 1B (CPT1B), SREBP1c and PPARγ (P < 0.01). In conclusion, dietary supplementation of RA or UA may increase fat deposition in muscle of finishing pigs by regulating lipid metabolism and gut microbiota.

Liquid Nanoparticles for Nanocatalytic Cancer Therapy.

Nanotechnology is revolutionizing cancer therapy, and catalyzes the emerging of ion-involved cancer-therapeutic modality, which unfortunately suffers from undesirable nanocarriers for efficient intracellular ion delivery. To radically extricate from this critical issue, the glutathione (GSH)-responsive organosilica network is employed to lock the liquid drops at the nanoscale via a general bottom-up strategy to achieve the systemic delivery of "ion drugs". In this work, a sulfate radical generation donor (Na2 S2 O8 ), as a paradigm "ion drug", is entrapped into this liquid nanoparticle for efficiently delivering to the tumor region. After further surface engineering with pH-responsive tannic acid-Fe2+ framework, these liquid nanoparticles achieve tumor-microenvironmental pH/GSH-dual responsive ion release (Fe2+ /Na+ /S2 O8 2- ) after reaching the tumor sites, where the Fe2+ further triggers S2 O8 2- to generate toxic •SO4 - and •OH, effectively executing cancer cell ferroptosis (Fe2+ , reactive oxygen species-ROS) and pyroptosis (Na+ , ROS). Such a tumor-responsive/specific liquid nanoplatform is highly instructive for further ion-mediated nanomedicine and disease treatment.

Protection against Metabolic Associated Fatty Liver Disease by Protocatechuic Acid.

Gut microbiota-diet interaction has been identified as a key factor of metabolic associated fatty liver disease (MAFLD). Recent studies suggested that dietary polyphenols may protect against MAFLD by regulating gut microbiota; however, the underlying mechanisms remain elusive. We first investigated the effects of cyanidin 3-glucoside and its phenolic metabolites on high-fat diet induced MAFLD in C57BL/6J mice, and protocatechuic acid (PCA) showed a significant positive effect. Next, regulation of PCA on lipid metabolism and gut microbiota were explored by MAFLD mouse model and fecal microbiota transplantation (FMT) experiment. Dietary PCA reduced intraperitoneal and hepatic fat deposition with lower levels of transaminases (AST & ALT) and inflammatory cytokines (IL-1ß, IL-2, IL-6, TNF-α & MCP-1), but higher HDL-c/LDL-c ratio. Characterization of gut microbiota indicated that PCA decreased the Firmicutes/Bacteroidetes ratio mainly by reducing the relative abundance of genus Enterococcus, which was positively correlated with the levels of LDL-c, AST, ALT and most of the up-regulated hepatic lipids by lipidomics analysis. FMT experiments showed that Enterococcus faecalis caused hepatic inflammation, fat deposition and insulin resistance with decreased expression of carnitine palmitoyltransferase-1 alpha (CPT1α), which can be reversed by PCA through inhibiting Enterococcus faecalis. Transcriptomics analysis suggested that Enterococcus faecalis caused a significant decrease in the expression of fibroblast growth factor 1 (Fgf1), and PCA recovered the expression of Fgf1 with insulin-like growth factor binding protein 2 (Igfbp2), insulin receptor substrate 1 (Irs1) and insulin receptor substrate 2 (Irs2). These results demonstrated that high proportion of gut Enterococcus faecalis accelerates MAFLD with decreased expression of CPT1α and Fgf1, which can be prevented by dietary supplementation of PCA.

Placental Malfunction, Fetal Survival and Development Caused by Sow Metabolic Disorder: The Impact of Maternal Oxidative Stress.

The energy and metabolic state of sows will alter considerably over different phases of gestation. Maternal metabolism increases dramatically, particularly in late pregnancy. This is accompanied by the development of an increase in oxidative stress, which has a considerable negative effect on the maternal and the placenta. As the only link between the maternal and the fetus, the placenta is critical for the maternal to deliver nutrients to the fetus and for the fetus' survival and development. This review aimed to clarify the changes in energy and metabolism in sows during different pregnancy periods, as well as the impact of maternal oxidative stress on the placenta, which affects the fetus' survival and development.

Engineering ROS-scavenging Prussian blue nanozymes for efficient atherosclerosis nanotherapy.

Atherosclerosis (AS), characterized by a chronic inflammatory disease, is a top cause of morbidity and disability worldwide. During the pathogenesis of AS, the leading process of inflammation highly involves a secondary event of oxidative stress, but limited antioxidants are currently available clinically due to their nonspecific effects, poor biosafety, and rapid in vivo elimination and urinary excretion as well as short retention time within plaque lesions. In this work, Prussian blue nanozymes with a strong reactive oxygen species (ROS)-scavenging ability were rationally engineered for efficient AS nanotherapy. Specifically, the obtained nanozymes with high photothermal performance could behave as potent photoacoustic imaging agents for plaque detection. In addition, these nanozymes featuring multienzyme activities could reduce the cellular ROS level, exert cytoprotective effects against ROS-mediated macrophages apoptosis, and inhibit foam cell formation, significantly boycotting AS development. The underlying mechanism was further verified by transcriptome sequencing at the cellular level and a series of immunohistochemical staining of aortic sinus sections in apoE-/- mice. Finally, the high biocompatibility and biosafety of the engineered Prussian blue nanozymes further guarantee their clinical translation potential for AS management.

Topology regulation of nanomedicine for autophagy-augmented ferroptosis and cancer immunotherapy.

Iron accumulation and lipid peroxidation form the basis of ferroptosis, potentially circumventing the limitations of apoptosis in cancer treatment. Owing to the lack of potent ferroptosis inducers, the development of efficient ferroptosis-based therapeutic agents and protocols against cancers is highly challenging. Inspired by the topological effect of nanoparticles in modulating cellular function/status, a specific tetrapod ferroptosis-inducer iron-palladium (FePd) nanocrystal was rationally engineered for physically activated autophagy-augmented ferroptosis and enhanced cancer immunotherapy. Specifically, the tetrapod FePd nanocrystal featured strong peroxidase-/glutathione oxidase-mimicking bioactivities, which promoted cancer cell ferroptosis. The special spiky morphology and nanostructure of the FePd nanocrystal simultaneously induced autophagy, which augmented ferroptosis in cancer cells and triggered the release of inflammatory cytokines in macrophages for strengthening anti-PD-L1-antibody mediated immunotherapy, synergistically achieving the maximal antineoplastic effect in three tumor-bearing animal models. This unique physical activation strategy for efficient cancer treatment via precise morphological tuning represents a paradigm for nanomedicine design for efficient tumor treatment.

Effect of dietary resveratrol on placental function and reproductive performance of late pregnancy sows.

Placental function is vital to the fetal growth of sows, and resveratrol (RES) can protect cells against oxidative stress, which is one of the major factors impairing placental function. This study aimed to investigate the effect of dietary resveratrol (RES) on placental function and reproductive performance during late pregnancy in a sow model from the aspects of oxidative stress, insulin resistance, and gut microbiota. A total of 26 hybrid pregnant sows (Landrace × Yorkshire) with similar parity were randomly allocated into two groups (n = 13) and fed with a basal diet or a diet containing 200 mg/kg of resveratrol from day 85 of gestation until parturition. The dietary supplementation of RES increased the litter weight at parturition by 12.53% (p = 0.145), with ameliorated insulin resistance (HOMA-IR), increased triglyceride (TG) levels, and decreased interleukin (IL)-1ß and IL-6 levels in serum (p < 0.05). Moreover, resveratrol increased the placental vascular density (p < 0.05) with the enhanced expression of nutrient transporter genes (SLC2A1 and SLC2A3) and antioxidant genes, such as superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) but declined the expression of inflammatory genes, such as IL-1ß and IL-6 (p < 0.05). The characterization of the fecal microbiota revealed that resveratrol decreased the relative abundance of the Christensensllaceae R-7 group and Ruminococcaceae UCG-008 (p < 0.05), which had a positive linear correlation with the expression of IL-1ß and IL-6 (p < 0.05), but had a negative linear correlation with the expression of SOD2, HO-1, SLC2A1, and SCL2A3 genes (p < 0.05). These data demonstrated that dietary supplementation with resveratrol can improve placental function with ameliorated insulin resistance, oxidative stress, and inflammation potentially by regulating Ruminococcaceae UCG-008 and the Christensensllaceae R-7 group in sows.

Living Macrophage-Delivered Tetrapod PdH Nanoenzyme for Targeted Atherosclerosis Management by ROS Scavenging, Hydrogen Anti-inflammation, and Autophagy Activation.

Atherosclerosis, driven by chronic inflammation in the artery walls, underlies several severe cardiovascular diseases. However, currently available anti-inflammatory-based strategies for atherosclerosis treatment suffer from compromised therapeutic efficacy and undesirable therapeutic outcome. Herein, a distinct tetrapod needle-like PdH nanozyme was designed and engineered for efficient atherosclerosis treatment by the combinatorial reactive oxygen species (ROS) scavenging, hydrogen anti-inflammation, and autophagy activation. After loading into macrophages and targeted delivery to arterial plaques, these multifunctional nanozymes efficiently decreased the ROS levels and significantly suppressed the inflammation-related pathological process, exerting the distinct antioxidation and anti-inflammatory performance for alleviating atherosclerosis development. Especially and importantly, the specific spiky morphology of the PdH nanoenzyme further triggered a strong autophagy response in macrophages, synergistically maintaining the cellular homeostasis and alleviating atherosclerosis development. Both in vitro and in vivo results confirmed the synergy among the antioxidation, anti-inflammatory, and autophagy activation, suggesting that the combinatorial engineering of nanomedicines with intrinsic multiple therapeutic functions and topology-induced biological effects is highly preferable and effective for achieving the high therapeutic performance and desirable therapeutic outcome on atherosclerosis management and therapy.

Effect of Eucommia ulmoides Leaf Extract on Growth Performance, Carcass Traits, Parameters of Oxidative Stress, and Lipid Metabolism in Broiler Chickens.

Eucommia ulmoides bark has been traditionally used as a Chinese medicine to attenuate stress, but the leaf, which is rich in polyphenols and polysaccharides, has been rarely used. This study aimed to investigate the effect of Eucommia ulmoides leaf extracts (EULEs) on oxidative stress and meat quality of broilers. A total of 252 broilers were randomly divided into 3 treatments and fed with a control basal diet (CON), or a diet containing 250 mg/kg or 1,000 mg/kg of EULE for 51 days. Results showed that dietary supplementation of 250 mg/kg EULE increased significantly the average daily gain of broilers in the early stage (1-21 days), while 250 mg/kg or 1,000 mg/kg of EULE decreased the feed conversion ratio in the whole period (P < 0.05). Supplementation of 250 mg/kg EULE reduced the level of MDA in the liver (P < 0.05), while 1,000 mg/kg EULE decreased the serum level of MDA (P < 0.05), and the HDL level in serum was increased by 250 mg/kg or 1,000 mg/kg EULE (P < 0.05). Additionally, 250 mg/kg EULE decreased abdominal fat ratio and serum triglyceride (TC) level in broilers, while 250 or 1,000 mg/kg of EULE reduced drip loss in breast muscle (P < 0.05), and 1,000 mg/kg EULE reduced the cooking loss in thigh muscle (P < 0.05). In conclusion, dietary supplementation of 250 mg/kg of EULE could attenuate oxidative stress and improve the growth performance and meat quality in broilers.

Engineering dual catalytic nanomedicine for autophagy-augmented and ferroptosis-involved cancer nanotherapy.

Chemodynamic therapy represents a distinct anti-tumor strategy by activating intratumoral chemical catalytic reactions to produce highly toxic reactive oxygen species (ROS) from non-/limited-toxic nanocatalysts. However, the low efficacy of ROS generation still remains a major challenge for further clinical translation. Herein, a liposomal nanosystem which simultaneously encapsulated copper peroxide nanodots (CPNs) and artemisinin (ART) was constructed for autophagy-enhanced and ferroptosis-involved cancer cell death owing to Cu-based dual catalytic strategy. To be specific, the CPN components, served as a H2O2 self-supplying platform, release H2O2 and Cu2+ under acidic tumor environment and endogenously generate .OH via Fenton-like reaction (catalytic reaction I). In addition, Cu2+ species catalyze ART components to produce ROS radicals (catalytic reaction II), further augmenting the intracellular oxidative damage and lipid peroxide accumulation, leading to cancer cell death. Specifically, ART also acted as a potent autophagy inducer increasing the level of intracellular iron pool through degradation of ferritin, which could promote cancer cell ferroptosis, producing the best antineoplastic effect. After accumulation into the tumor sites, ultrasound irradiation was applied to trigger the release of CPNs and ART from liposomal nanosystems, and amplify the efficacy of catalytic reaction for maximum therapeutic effect. Both in vitro and in vivo therapeutic outcomes suggest the outstanding autophagy-augmented ferroptosis-involved cancer-therapeutic efficacy, which was further corroborated by transcriptome sequencing. In this work, Cu was firstly proven to trigger ART to produce ROS species, but also provide a TME-responsive nanoplatform for potentially suppressing tumor growth by autophagy-augmented ferroptosis-involved cancer nanotherapy.

Dietary ferulic acid and vanillic acid on inflammation, gut barrier function and growth performance in lipopolysaccharide-challenged piglets.

Ferulic acid (FA) and vanillic acid (VA) are considered as major phenolic metabolites of cyanidin 3-glucoside, a polyphenol that widely exists in plants that possess a protective effect against oxidative stress and inflammation in our previous study. This study aimed to investigate the effect of FA and VA on inflammation, gut barrier function, and growth performance in a weaned piglet model challenged with lipopolysaccharide (LPS). Thirty-six piglets (PIC 337 × C48, 28 d of age) were randomly allocated into 3 treatments with 6 replicate pens (2 piglets per pen). They were fed with a basal diet or a diet containing 4,000 mg/kg of FA or VA. Dietary supplementation of VA significantly increased average daily gain (ADG) (P < 0.05). Both FA and VA decreased serum levels of thiobarbituric acid reactive substances (TBARS), interlukin (IL)-1ß, IL-2, IL-6, and tumor necrosis factor (TNF)-α (P < 0.05), and enhanced the expression of tight junction protein oclaudin (P < 0.05). Analysis of gut microbiota indicated that both FA and VA increased the Firmicutes/Bacteroidetes ratio alongside reducing the relative abundance of the Prevotellaceae family including Prevotella 9 and Prevotella 2 genera, but enriched the Lachoiraceaea family including the Lachnospiraceae FCS020 group (P < 0.05). Moreover, VA reduced the relative abundance of Prevotella 7 and Prevotella 1 but enriched Lachnospira, Eubacterium eligens group, and Eubacterium xylanophilum group (P < 0.05), while FA showed a limited effect on these genera. The results demonstrated that both VA and FA could alleviate inflammation and oxidative stress, but only VA has a significant positive effect on the growth performance of LPS-challenged piglets potentially through modulating gut microbiota.

Dietary ß-Carotene on Postpartum Uterine Recovery in Mice: Crosstalk Between Gut Microbiota and Inflammation.

As the precursor of vitamin A, ß-carotene has a positive effect on reproductive performance. Our previous study has shown that ß-carotene can increase antioxidant enzyme activity potentially through regulating gut microbiota in pregnant sows. This study aimed to clarify the effect of ß-carotene on reproductive performance and postpartum uterine recovery from the aspect of inflammation and gut microbiota by using a mouse model. Twenty-seven 6 weeks old female Kunming mice were randomly assigned into 3 groups (n=9), and fed with a diet containing 0, 30 or 90 mg/kg ß-carotene, respectively. The results showed that dietary supplementation of ß-carotene reduced postpartum uterine hyperemia and uterine mass index (P<0.05), improved intestinal villus height and villus height to crypt depth ratio, decreased serum TNF-α and IL-4 concentration (P<0.05), while no differences were observed in litter size and litter weight among three treatments. Characterization of gut microbiota revealed that ß-carotene up-regulated the relative abundance of genera Akkermansia, Candidatus Stoquefichus and Faecalibaculum, but down-regulated the relative abundance of Alloprevotella and Helicobacter. Correlation analysis revealed that Akkermansia was negatively correlated with the IL-4 concentration, while Candidatus Stoquefichus and Faecalibaculum had a negative linear correlation with both TNF-α and IL-4 concentration. On the other hand, Alloprevotella was positively correlated with the TNF-α, and Helicobacter had a positive correlation with both TNF-α and IL-4 concentration. These data demonstrated that dietary supplementation of ß-carotene contributes to postpartum uterine recovery by decreasing postpartum uterine hemorrhage and inhibiting the production of inflammatory cytokines potentially through modulating gut microbiota.

Engineering two-dimensional silicene composite nanosheets for dual-sensitized and photonic hyperthermia-augmented cancer radiotherapy.

The rapid development of nanotechnology has triggered the emerging of tremendous theranostic nanoplatforms for combating cancers. Silicene, as an emerging two-dimensional (2D) material, has been recently explored as therapeutic agent due to their desirable biodegradation and strong photothermal-conversion performance. However, the rational design of silicene-based composites for further exerting multifunctional medical applications is still highly challenging. Herein, we report on the construction of silicene-based silicene@Pt composite nanosheets for computed tomography (CT)/photoacoustic (PA) imaging-guided dual-sensitized radiotherapy combined with photonic tumor hyperthermia, which has been achieved by a seed-growth approach to in situ grow Pt components onto silicene nanosheets' surface. Especially, by functionalization of Pt components, these nanosheets could act as both contrast agents for CT imaging and dual radio-sensitizing agents for radiotherapy, which could deposit Pt-involved radiation energy (sensitized therapeutic process I) and overcome hypoxia-associated radio-resistance by Pt-catalytic O2 generation from overexpressed H2O2 within the tumor microenvironment (sensitized therapeutic process II). The strong photothermal-conversion performance of silicene nanosheets not only endowed silicene@Pt composite nanosheets with photoacoustic imaging property, but also realized the photonic tumor hyperthermia and achieved a combined therapeutic effect with radiotherapy. This work not only broadens the biomedical applications of silicene, but also develops functionalization strategies of silicene for versatile biomedical applications.

Modulation of Gut Microbiota and Oxidative Status by ß-Carotene in Late Pregnant Sows.

Recent evidences suggest that gut microbiota plays an important role in regulating physiological and metabolic activities of pregnant sows, and ß-carotene has a potentially positive effect on reproduction, but the impact of ß-carotene on gut microbiota in pregnant sows remains unknown. This study aimed to explore the effect and mechanisms of ß-carotene on the reproductive performance of sows from the aspect of gut microbiota. A total of 48 hybrid pregnant sows (Landrace × Yorkshire) with similar parity were randomly allocated into three groups (n = 16) and fed with a basal diet or a diet containing 30 or 90 mg/kg of ß-carotene from day 90 of gestation until parturition. Dietary supplementation of 30 or 90 mg/kg ß-carotene increased the number of live birth to 11.82 ± 1.54 and 12.29 ± 2.09, respectively, while the control group was 11.00 ± 1.41 (P = 0.201). Moreover, ß-carotene increased significantly the serum nitric oxide (NO) level and glutathione peroxidase (GSH-Px) activity (P < 0.05). Characterization of fecal microbiota revealed that 90 mg/kg ß-carotene increased the diversity of the gut flora (P < 0.05). In particular, ß-carotene decreased the relative abundance of Firmicutes including Lachnospiraceae AC2044 group, Lachnospiraceae NK4B4 group and Ruminococcaceae UCG-008, but enriched Proteobacteria including Bilophila and Sutterella, and Actinobacteria including Corynebacterium and Corynebacterium 1 which are related to NO synthesis. These data demonstrated that dietary supplementation of ß-carotene may increase antioxidant enzyme activity and NO, an important vasodilator to promote the neonatal blood circulation, through regulating gut microbiota in sows.

Dietary protocatechuic acid ameliorates inflammation and up-regulates intestinal tight junction proteins by modulating gut microbiota in LPS-challenged piglets.

BACKGROUND: Weaning is one of the major factors that cause stress and intestinal disease in piglets. Protocatechuic acid (PCA) is an active plant phenolic acid which exists in Chinese herb, Duzhong (Eucommia ulmoides Oliver), and is also considered as the main bioactive metabolite of polyphenol against oxidative stress and inflammation. This study aimed to investigate the effect of PCA on growth performance, intestinal barrier function, and gut microbiota in a weaned piglet model challenged with lipopolysaccharide (LPS). METHODS: Thirty-six piglets (Pig Improvement Company line 337 × C48, 28 d of age, 8.87 kg ± 0.11 kg BW) were randomly allocated into 3 treatments and fed with a basal diet (CTL), a diet added 50 mg/kg of aureomycin (AUR), or a diet supplemented with 4000 mg/kg of PCA, respectively. The piglets were challenged with LPS (10 µg/kg BW) on d 14 and d 21 by intraperitoneal injection during the 21-d experiment. Animals (n = 6 from each group) were sacrificed after being anesthetized by sodium pentobarbital at 2 h after the last injection of LPS. The serum was collected for antioxidant indices and inflammatory cytokines analysis, the ileum was harvested for detecting mRNA and protein levels of tight junction proteins by PCR and immunohistochemical staining, and the cecum chyme was collected for intestinal flora analysis using 16S rRNA gene sequencing. RESULTS: Dietary supplementation of PCA or AUR significantly increased the expression of tight junction proteins including ZO-1 and claudin-1 in intestinal mucosa, and decreased the serum levels of thiobarbituric acid reactive substances (TBARS) and IL-6, as compared with CTL group. In addition, PCA also decreased the serum levels of IL-2 and TNF-α (P < 0.05). Analysis of gut microbiota indicated that PCA increased the Firmicutes/Bacteroidetes ratio (P < 0.05). Spearman's correlation analysis at the genus level revealed that PCA reduced the relative abundance of Prevotella 9, Prevotella 2, Holdemanella, and Ruminococcus torques group (P < 0.05), and increased the relative abundance of Roseburia and Desulfovibrio (P < 0.05), whereas AUR had no significant effect on these bacteria. CONCLUSIONS: These results demonstrated that both PCA and AUR had protective effect on oxidative stress, inflammation and intestinal barrier function in piglets challenged with LPS, and PCA potentially exerted the protective function by modulating intestinal flora in a way different from AUR.

Defect engineering of 2D BiOCl nanosheets for photonic tumor ablation.

Photothermal therapy (PTT) is an emerging technology as a noninvasive therapeutic modality for inducing photonic cancer hyperthermia. However, current photothermal conversion agents suffer from low therapeutic efficiency and single functionality. Engineering crystal defects on the surface or substrate of semiconductors can substantially enhance their optical absorption capability as well as improve their photothermal effects in theranostic nanomedicines. In this study, a specific defect engineering strategy was developed to endow two-dimensional (2D) BiOCl nanosheets with intriguing photothermal conversion performance by creating oxygen vacancies on the surface (O-BiOCl). Importantly, the photothermal performance and photoacoustic imaging capability of the 2D O-BiOCl nanosheets could be precisely controlled by modulating the amounts of oxygen vacancies. The strong Bi-based X-ray attenuation coefficient endowed these nanosheets with the contrast-enhanced computed tomography imaging capability. The high near-infrared-triggered photonic hyperthermia for tumor ablation was systematically demonstrated both in vitro at the cellular level and in vivo for tumor breast cancer mice xenograft models. Based on the demonstrated high biocompatibility of these 2D O-BiOCl nanosheets, this work not only formulates an intriguing 2D photothermal nanoagent for tumor ablation, but also provides an efficient strategy to control the photothermal performance of nanoagents by defect engineering.

Dietary resveratrol supplementation inhibits heat stress-induced high-activated innate immunity and inflammatory response in spleen of yellow-feather broilers.

The aim of this study was to investigate the effect of dietary resveratrol supplementation on innate immunity and inflammatory responses in the spleen of yellow-feather broilers under heat stress. A total of 288 yellow-feather broilers of 28-day-old were randomly assigned to 3 treatment groups with 6 replicates. A thermo-neutral group (TN) (24 ± 2°C) received a basal diet and another 2 heat-stressed groups (37 ± 2°C for 8 h/D and 24 ± 2°C for the remaining time) were fed the basal diet (HT) or basal diet with 500 mg/kg resveratrol (HT+Res) for 14 consecutive days. The results showed that heat stress decreased (P < 0.05) the growth index of thymus, spleen, and bursa of Fabricius, reduced (P < 0.05) the levels of complement C3 and C4 in serum. Heat stress also caused activation of inflammatory immune responses evidenced by increased (P < 0.05) the mRNA abundance of HSP (heat shock protein) 70, toll-like receptor (TLR)1, TLR4, TLR5, myeloid differentiation factor-88 (MyD88), nucleotide-binding oligomerization domain 1 (NOD1), Dectin-1, transforming growth factor-ß-activated kinase 1 (TAK1), interleukin (IL)-1, IL-4, IL-6, and tumor necrosis factor (TNF)-α, but decreased the mRNA abundance of interferon (IFN)-γ, activated nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), and phosphoinositide-3 kinases-protein kinase B (PI3K/AKT) signaling pathways. Dietary supplementation with resveratrol improved (P < 0.05) the growth index of thymus, spleen and bursa Fabricius, and increased (P < 0.05) the serum level of complement C3 under heat stress. In addition, resveratrol reduced (P < 0.05) the mRNA abundance of HSP70, TLR4, TLR5, NOD1, Dectin-1, and TAK1, and inhibited the NF-κB, MAPK and PI3K/AKT signaling pathway via down-regulated the phosphorylation of p65, extracellular signal-regulated kinases 1/2, c-Jun N-terminal protein kinase and AKT, as well as decreased the inflammatory cytokines expression, including IL-1, IL-4, IL-6, and TNF-α in the spleen under heat stress. Collectively, dietary resveratrol could have beneficial effects to regulate innate immunity and inflammatory response, via inhibiting the activation of NF-κB, MAPK, and PI3K/AKT signaling pathways induced by heat stress in the spleen.