Dietary honokiol supplementation improves antioxidant capacity, enhances intestinal health, and modulates cecal microbial composition and function of broiler chickens.

Honokiol is a multifunctional polyphenol present in Magnolia officinalis. The effects of honokiol as a supplement in broiler chicken diets, and the underlying mechanisms, remain unclear. Therefore, the aim of the present study was to investigate the effects of honokiol on the growth performance, antioxidant capacity, and intestinal histomorphology of broiler chickens and to explore the underlying mechanisms. In total, 240 one-day-old broilers were randomly allocated to 5 dietary treatments, with 6 replicate pens and 8 birds per pen. Birds were fed a basal diet supplemented with 0 (blank control, BC), 100, 200, or 400 mg/kg honokiol (H100, H200, and H400), or 200 mg/kg bacitracin zinc (PC) for 42 d. The results showed that H200 and H400 increased body weight gain (BWG) and decreased feed conversion ratio (FCR) during the starter period (P < 0.05). H100 and H200 increased total superoxide dismutase (T-SOD) activity in the serum and decreased malondialdehyde (MDA) amount in the jejunum on d 42 (P < 0.05). Moreover, H100 increased villus height-to-crypt depth ratio in both the jejunum and ileum on d 21 (P < 0.05). PCR analysis showed that honokiol upregulated intestinal expression of glutathione peroxidase (GSH-Px) and downregulated intestinal expression of inducible nitric oxide synthase (iNOS) on d 42 (P < 0.05). The Shannon index, which represents the microbial alpha diversity, was reduced for the PC, H200, and H400 groups. Notably, honokiol treatment altered the cecal microbial community structure and promoted the enrichment of several bacteria, including Firmicutes and Lactobacillus. Higher production of short-chain fatty acids was observed in the cecal digesta of H100 birds, accompanied by an enriched glycolysis/gluconeogenesis pathway, according to the functional prediction of the cecal microbiota. This study provides evidence that honokiol improves growth performance, antioxidant capacity, and intestinal health of broiler chickens, possibly by manipulating the composition and function of the microbial community.

Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Combined Effects of Cadmium and Lead on Growth Performance and Kidney Function in Broiler Chicken.

Cadmium (Cd) and lead (Pb) are heavy metals prevalent in the environment and feed, and they reduce production performance of domestic animals, as well as they result in residue in animal tissues. The kidney is the target tissue for Cd and Pb. And the kidney is crucial for the reabsorption of calcium (Ca), which consequently influences bone strength. However, there are relatively few studies related to the effects of Cd and Pb exposure on performance, bone strength and kidney damage in livestock. The purpose of this experiment was to explore the combined effect of Cd and Pb on growth performance and renal impairment and the possible underlying mechanism. For this, 168 1-day-old Ross 308 broilers were randomly divided into four groups of six birds each, with seven replicates in each group: control group, 50 mg Cd/kg body weight group, 200 mg Pb/kg body weight group and 50 mg Cd/kg body weight + 200 mg Pb/kg body weight group. Feed intake was recorded daily and body weight was recorded weekly. The results show that at the end of the 3rd and 6th week, one broiler from each replicate was randomly selected for sampling. Boilers co-exposed to Cd and Pb for 3 weeks and 6 weeks had significantly decreased average daily feed intake (ADFI) and average daily body weight gain (ADG) than the control group, and the ratio of feed-to-weight gain (F/G) significantly increased after 6 weeks of co-exposure to Cd and Pb. Microscopic picture and ultrastructure analyses of the kidneys showed that Cd and Pb caused kidney damage to broiler chickens, and the damage was more serious in the Cd + Pb group, which was manifested by increased renal tubular epithelial degeneration and increased interstitial stasis points. Dietary exposure to Cd and Pb impaired production performance and induced renal oxidative damage in broilers. The combined effects of Cd and Pb on the kidneys are greater than their effects alone. The PERK-ATF4 pathway mediated endoplasmic reticulum stress participates the renal oxidative damage during chronic Cd and Pb exposure.

Inflammation-Responsive Hydrogel Accelerates Diabetic Wound Healing through Immunoregulation and Enhanced Angiogenesis.

Angiogenesis is a prominent component during the highly regulated process of wound healing. The application of exogenous vascular endothelial growth factor (VEGF) has shown considerable potential in facilitating angiogenesis. However, its effectiveness is often curtailed due to chronic inflammation and severe oxidative stress in diabetic wounds. Herein, an inflammation-responsive hydrogel incorporating Prussian blue nanoparticles (PBNPs) is designed to augment the angiogenic efficacy of VEGF. Specifically, the rapid release of PBNPs from the hydrogel under inflammatory conditions effectively alleviates the oxidative stress of the wound, therefore reprogramming the immune microenvironment to preserve the bioactivity of VEGF for enhanced angiogenesis. In vitro and in vivo studies reveal that the PBNPs and VEGF co-loaded hydrogel is biocompatible and possesses effective anti-inflammatory properties, thereby facilitating angiogenesis to accelerate the wound healing process in a type 2 diabetic mouse model.

The Effect of Enteric-Derived Lipopolysaccharides on Obesity.

Endotoxin is a general term for toxic substances in Gram-negative bacteria, whose damaging effects are mainly derived from the lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, and is a strong pyrogen. Obesity is a chronic, low-grade inflammatory condition, and LPS are thought to trigger and exacerbate it. The gut flora is the largest source of LPS in the body, and it is increasingly believed that altered intestinal microorganisms can play an essential role in the pathology of different diseases. Today, the complex axis linking gut flora to inflammatory states and adiposity has not been well elucidated. This review summarises the evidence for an interconnection between LPS, obesity, and gut flora, further expanding our understanding of LPS as a mediator of low-grade inflammatory disease and contributing to lessening the effects of obesity and related metabolic disorders. As well as providing targets associated with LPS, obesity, and gut flora, it is hoped that interventions that combine targets with gut flora address the individual differences in gut flora treatment.

Mesoporous Silicon Nanoparticles with Liver-Targeting and pH-Response-Release Function Are Used for Targeted Drug Delivery in Liver Cancer Treatment.

This article aims to develop an aspirin-loaded double-modified nano-delivery system for the treatment of hepatocellular carcinoma. In this paper, mesoporous silica nanoparticles (MSN) were prepared by the "one-pot two-phase layering method", and polydopamine (PDA) was formed by the self-polymerization of dopamine as a pH-sensitive coating. Gal-modified PDA-modified nanoparticles (Gal-PDA-MSN) were synthesized by linking galactosamine (Gal) with actively targeted galactosamine (Gal) to PDA-coated MSN by a Michael addition reaction. The size, particle size distribution, surface morphology, BET surface area, mesoporous size, and pore volume of the prepared nanoparticles were characterized, and their drug load and drug release behavior in vitro were investigated. Gal-PDA-MSN is pH sensitive and targeted. MSN@Asp is different from the release curves of PDA-MSN@Asp and Gal-PDA-MSN@Asp, the drug release of PDA-MSN@Asp and Gal-PDA-MSN@Asp accelerates with increasing acidity. In vitro experiments showed that the toxicity and inhibitory effects of the three nanodrugs on human liver cancer HepG2 cells were higher than those of free Asp. This drug delivery system facilitates controlled release and targeted therapy.

Gut-Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a liver disease that remains difficult to predict and diagnose, and the underlying mechanisms are yet to be fully clarified. The gut-liver axis refers to the reciprocal interactions between the gut and the liver, and its homeostasis plays a prominent role in maintaining liver health. It has been recently reported that patients and animals with DILI have a disrupted gut-liver axis, involving altered gut microbiota composition, increased intestinal permeability and lipopolysaccharide translocation, decreased short-chain fatty acids production, and impaired bile acid metabolism homeostasis. The present review will summarize the evidence from both clinical and preclinical studies about the role of the gut-liver axis in the pathogenesis of DILI. Moreover, we will focus attention on the potential therapeutic strategies for DILI based on improving gut-liver axis function, including herbs and phytochemicals, probiotics, fecal microbial transplantation, postbiotics, bile acids, and Farnesoid X receptor agonists.

DTI-MR fingerprinting for rapid high-resolution whole-brain T1 , T2 , proton density, ADC, and fractional anisotropy mapping.

PURPOSE: This study aims to develop a high-efficiency and high-resolution 3D imaging approach for simultaneous mapping of multiple key tissue parameters for routine brain imaging, including T1 , T2 , proton density (PD), ADC, and fractional anisotropy (FA). The proposed method is intended for pushing routine clinical brain imaging from weighted imaging to quantitative imaging and can also be particularly useful for diffusion-relaxometry studies, which typically suffer from lengthy acquisition time. METHODS: To address challenges associated with diffusion weighting, such as shot-to-shot phase variation and low SNR, we integrated several innovative data acquisition and reconstruction techniques. Specifically, we used M1-compensated diffusion gradients, cardiac gating, and navigators to mitigate phase variations caused by cardiac motion. We also introduced a data-driven pre-pulse gradient to cancel out eddy currents induced by diffusion gradients. Additionally, to enhance image quality within a limited acquisition time, we proposed a data-sharing joint reconstruction approach coupled with a corresponding sequence design. RESULTS: The phantom and in vivo studies indicated that the T1 and T2 values measured by the proposed method are consistent with a conventional MR fingerprinting sequence and the diffusion results (including diffusivity, ADC, and FA) are consistent with the spin-echo EPI DWI sequence. CONCLUSION: The proposed method can achieve whole-brain T1 , T2 , diffusivity, ADC, and FA maps at 1-mm isotropic resolution within 10 min, providing a powerful tool for investigating the microstructural properties of brain tissue, with potential applications in clinical and research settings.

Dietary Morus alba L. leaf supplementation improves hepatic lipid accumulation of laying hens via downregulating CircACACA.

Fatty liver hemorrhagic syndrome (FLHS) is the most common metabolic disease in laying hens. Morus alba L. (mulberry) leaf has the effect of regulating lipid metabolism. We evaluated the effects of dietary 3% mulberry leaf (MUL) supplementation in production performance, egg quality, and liver lipid deposition in laying hens. Differentially expressed genes and circRNAs in the liver were identified using whole-transcriptome sequencing. We also evaluated the effects of the MUL extract using an in vitro model of primary hepatocytes induced by free fatty acids and explored the role of key circRNAs in this process. Dietary supplementation with 3% MUL alleviated liver steatosis in laying hens, as shown by decreased fatty liver color score, relative liver weight (P < 0.01), and triglyceride levels (P < 0.05), and showed a tendency to reduce the mortality rate of laying hens (P = 0.09). In addition, mulberry leaf supplementation significantly reduced cholesterol content in egg yolk (P < 0.01). Dietary mulberry leaf supplementation downregulated the expression of genes involved in fatty acid and cholesterol biosynthesis, and upregulated the expression of fatty acid oxidation-related genes in the liver. CircACACA, which is derived from exons 2 and 3 of the acetyl-CoA carboxylase alpha (ACACA) pre-mRNA, was significantly reduced in the MUL group (P < 0.01). Upregulation of circACACA expression reversed the lipid-lowering effect of mulberry leaf extract by upregulating sterol regulatory element-binding proteins 1 c (SREBP-1c) and fatty acid synthase (FASN) (P < 0.05). Overall, mulberry leaf is an effective therapeutic strategy for FLHS in hens and can improve liver lipid metabolism by downregulating circACACA.

Lactobacillus rhamnosus GG aggravates vascular calcification in chronic kidney disease: A potential role for extracellular vesicles.

AIMS: Lactobacillus rhamnosus GG (LGG) is a probiotic with great promise in future clinical application, which can significantly promote bone formation. However, the effect of LGG on CKD-related vascular calcification is unclear. In this study, we aimed to investigate the effect of LGG on CKD-related vascular calcification. MATERIALS AND METHODS: After 2 weeks of 5/6 nephrectomy, CKD rats received a special diet (4 % calcium and 1.8 % phosphate) combined with 1,25-dihydroxyvitamin D3 to induce vascular calcification. Meanwhile, CKD rats in the LGG group were gavaged orally with LGG (1 × 109 CFU bacteria/day). 16S RNA amplicon sequencing was performed to analyze the effect of LGG treatment on gut microbiota composition. Furthermore, differential ultracentrifugation was utilized to extract EVs. The effects of EVs on vascular calcification were evaluated in rat VSMCs, rat aortic rings, and CKD rat calcification models. In this study, vascular calcification was assessed by microcomputed tomography analysis, alizarin red staining, calcium content determination, and the expression of osteogenic transcription factors RUNX2 and BMP2. KEY FINDINGS: LGG remarkably aggravated vascular calcification. LGG supplementation significantly altered gut microbiota composition in CKD rats, particularly increasing Lactobacillus. Interestingly, EVs presented a significant promoting effect on the development of calcification. Finally, mechanistic analysis proved that EVs aggravated vascular calcification through PI3K/AKT signaling. SIGNIFICANCE: These results do not support the supplementation of LGG in CKD-associated vascular calcification patients. Our study presented a fresh perspective on LGG with potential risks and adverse effects. CKD patients should use specific probiotic strains cautiously.

Maternal Magnolol Supplementation during Pregnancy and Lactation Promotes Antioxidant Capacity, Improves Gut Health, and Alters Gut Microbiota and Metabolites of Weanling Piglets.

Maternal nutrition exerts a profound effect on the postnatal performance of offspring, especially during the weaning period. The multifunctional bioactive component magnolol (MAG) has shown promise as a dietary supplement. This study aimed to explore the effects of maternal MAG supplementation on the antioxidant capacity, gut health, gut microbiome, and metabolome composition of weanling piglets. Fifty pregnant sows were randomly divided into two equally sized groups, the control group and the group supplemented with 100 g/t MAG during the gestation and lactation periods, and 7 days postweaning, the pups were euthanized. The microbiome and metabolome features of weanling piglet colons were compared. Our results revealed that maternal MAG supplementation modified the serum redox status of weanling piglets by decreasing malondialdehyde concentration and increasing superoxide dismutase activity and total antioxidant capacity. Moreover, the decreased indicators of diarrhea were accompanied by improved gut barrier function, in which serum diamine oxidase concentration was decreased, and expressions of zona occludens-1, claudin-1, and intestinal alkaline phosphatase were increased in the colon of weanling piglets from sows supplemented with MAG. Further analysis of the gut microbiota indicated that maternal MAG supplementation significantly increased the relative abundance of beneficial bacteria in the colon of weanling piglets, including Faecalibacterium prausnitzii and Oscillospira. Metabolome analysis identified 540 differential metabolites in the colon of piglets from MAG-fed dams, of which glycerophospholipid classes were highly correlated with progeny gut health and key beneficial bacteria. Our findings indicated that maternal MAG supplementation can improve the oxidative status and gut health of weanling piglets, possibly due to alterations in the gut microbiota and metabolites.

Corrigendum to "Antibacterial coaxial hydro-membranes accelerate diabetic wound healing by tuning surface immunomodulatory functions" [Mater. Today Bio, 16 (2022)].

[This corrects the article DOI: 10.1016/j.mtbio.2022.100395.].

Influence of SLCO1B1 Polymorphisms on the Pharmacokinetics of Mycophenolic Acid in Renal Transplant Recipients.

OBJECTIVE: This study was designed to analyze the correlation between single nucleotide polymorphisms (SNP) related to drug metabolism and pharmacokinetics of mycophenolic acid (MPA) during long-term follow-up. MATERIALS AND METHOD: A retrospective cohort study involving 71 renal transplant recipients was designed. Blood samples were collected to extract total DNAs, followed by target sequencing based on next-generation sequencing technology. The MPA area under the curve (AUC) was calculated according to the formula established in our center. The general linear model and linear regression model were used to analyze the association between SNPs and MPA AUC. RESULTS: A total of 689 SNPs were detected in our study, and 90 tagger SNPs were selected after quality control and linkage disequilibrium analysis. The general linear model analysis showed that 9 SNPs significantly influenced MPA AUC. A forward linear regression was conducted, and the model with the highest identical degree (r2=0.55) included 4 SNPs (SLCO1B1: rs4149036 [P < 0.0001], ABCC2: rs3824610 [P = 0.005], POR: rs4732514 [P = 0.006], ABCC2: rs4148395 [P = 0.007]) and 6 clinical factors (age [P < 0.0001], gender [P < 0.0001], the incident of acute rejection (AR) [P = 0.001], albumin [P < 0.0001], duration after renal transplantation [P = 0.01], lymphocyte numbers [P = 0.026]). The most relevant SNP to MPA AUC in this model was rs4149036. The subgroup analysis showed that rs4149036 had a significant influence on MPA AUC in the older group (P = 0.02), high-albumin group (P = 0.01), male group (P = 0.046), and both within-36-month group (P = 0.029) and after-36-month group (P = 0.041). The systematic review included 4 studies, and 2 of them showed that the mutation in SLCO1B1 resulted in lower MPA AUC, which was contrary to our study. CONCLUSION: A total of 4 SNPs (rs4149036, rs3824610, rs4148395, and rs4732514) were identified to be significantly correlated with MPA AUC. Rs4149036, located in SLCO1B1, was suggested to be the most relevant SNP to MPA AUC, which had a stronger influence on recipients who were elder, male, or with high serum albumin. Furthermore, 6 clinical factors, including age, gender, occurrence of acute rejection, serum albumin, time from kidney transplantation, and blood lymphocyte numbers, were found to affect the concentration of MPA.

T-2 toxin-induced intestinal damage with dysregulation of metabolism, redox homeostasis, inflammation, and apoptosis in chicks.

T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.

A Comparison between Vitamin D3 and 25-Hydroxyvitamin D3 on Laying Performance, Eggshell Quality and Ultrastructure, and Plasma Calcium Levels in Late Period Laying Hens.

The objective of this study was to compare high supplementary doses (125 µg/kg) of vitamin D3 (VD3) or 25-hydroxyvitamin D3 (25-OHD3) with commercial supplementary doses (62.5 µg/kg) of VD3 on laying performance, eggshell quality and ultrastructure, and plasma calcium levels in late period laying hens. A total of 1512 Roman Gray (60-week-old) laying hens were allotted into three treatments with 12 replicates and 42 birds in each replicate. During the 12-week trial period, the layers were fed a basal diet supplemented with different doses of VD3 or 25-OHD3 (62.5 µg/kg VD3 in control group, CON; 125 µg/kg VD3 in high level VD3 group, VD3; 125 µg/kg 25-OHD3 in high level 25-OHD3 group, 25-OHD3). The results showed that high supplementary doses of VD3 or 25-OHD3 increased laying rate (p < 0.05). Moreover, the layers fed high doses of VD3 or 25-OHD3 diets had decreased unqualified egg rate and mortality (p < 0.05). High supplementary doses of VD3 or 25-OHD3 increased eggshell strength and eggshell thickness (p < 0.05). From observation in eggshell ultrastructure, high doses of VD3 or 25-OHD3 diets increased the palisade layer thickness and mammillary knob density (p < 0.05). Furthermore, high doses of VD3 or 25-OHD3 diets increased the calcium levels in plasma (p < 0.05). In summary, compared with 62.5 µg/kg doses of VD3, supplementary 125 µg/kg doses of VD3 or 25-OHD3 improved the laying performance, eggshell quality, and plasma calcium levels in late period laying hens. Additionally, there was an equal effect on laying performance and eggshell quality in the hens fed dietary 125 µg/kg doses of VD3 or 25-OHD3.

Construction of a Band-Aid Like Cardiac Patch for Myocardial Infarction with Controllable H2 S Release.

Excessive or persistent inflammation incites cardiomyocytes necrosis by generating reactive oxygen species in myocardial infarction (MI). Hydrogen sulfide (H2 S), a gaseous signal molecule, can quickly permeate cells and tissues, growing concerned for its cardioprotective effects. However, short resident time and strong side effects greatly restrict its application. Herein, a complex scaffold (AAB) is first developed to slowly release H2 S for myocardial protection by integrating alginate modified with 2-aminopyridine-5-thiocarboxamide (H2 S donor) into albumin electrospun fibers. Next, a band-aid like patch is constructed based on AAB (center) and nanocomposite scaffold which comprises albumin scaffold and black phosphorus nanosheets (BPNSs). With near-infrared laser (808 nm), thermal energy generated by BPNSs can locally change the molecular structure of fibrous scaffold, thereby attaching patch to the myocardium. In this study, it is also demonstrated that AAB can enhance regenerative M2 macrophage and attenuate inflammatory polarization of macrophages via reduction in intracellular ROS. Eventually, this engineered cardiac patch can relieve inflammation and promote angiogenesis after MI, and thereby recover heart function, providing a promising therapeutic strategy for MI treatment.

Effects of Chitosan Oligosaccharide on Production Performance, Egg Quality and Ovarian Function in Laying Hens with Fatty Liver Syndrome.

This study aimed to investigate the role of chitosan oligosaccharide (COS) as an additive in the feed of laying hens with fatty liver syndrome (FLS). Effects on production performance, egg quality as well as ovarian function were determined. A total of 360 Lohmann Pink-shell laying hens (28 weeks old) were randomly assigned to 5 groups (6 replicates × 12 birds). Hens were fed with a basal diet and a high-energy low-protein (HELP) diet supplemented with 0, 200, 400 and 800 mg/kg COS. COS reversed the lowered laying rates, increased feed-to-egg ratios and decreased albumen heights and Haugh units induced by the HELP diet. Additionally, COS improved the ovarian morphologies damaged by the HELP diet. Furthermore, COS enhanced antioxidant enzyme activities, reduced malonaldehyde levels and downregulated the mRNA expressions of nuclear factor kappa B, pro-inflammation cytokine genes and pro-apoptosis-related genes, while it upregulated the mRNA expression of anti-apoptosis-related genes in the ovaries of HELP-diet-fed hens. These findings suggested that dietary COS supplementation could improve production performance and egg quality in laying hens with FLS, and these beneficial effects were linked to improved ovarian morphology, which was attributed to decreased oxidative stress, inflammation and apoptosis in the ovaries.

Antibacterial coaxial hydro-membranes accelerate diabetic wound healing by tuning surface immunomodulatory functions.

Diabetic foot ulcers, typical non-healing wounds, represent a severe clinical problem. Advanced glycation end-products (AGEs), which create a prolonged pro-inflammatory micro-environment in defective sites, can be responsible for refractoriness of these ulcers. Macrophages are polarized to the M2 phenotype to facilitate the transition from a pro-inflammatory microenvironment to an anti-inflammatory microenvironment, which has been demonstrated to be an effective way to accelerate diabetic wound closure. Herein, we developed coaxial hydro-membranes mimicking the extracellular matrix structure that are capable of anti-inflammatory and antibacterial functions for diabetic wound repair. These fibrous membranes maintain a moist microenvironment to support cell proliferation. Macrophages grow in an elongated shape on the surface of the fibrous membranes. The fibrous membranes effectively impaired macrophage AGE-induced M1 polarization and induced macrophage polarization towards the M2 phenotype. The effects of the fibrous membranes on the interactions between macrophages and repair cells under a diabetic condition were also investigated. Furthermore, in vivo results from a full-thickness diabetic wound model confirmed the potential of the coaxial hydro-membranes to accelerate wound healing. This study's results indicate that the developed bioactive anti-inflammatory and antibacterial wound dressing can affect AGE-induced macrophage activation and crosstalk between macrophages and fibroblasts for treating diabetic wounds.

Prevalence and Incidence of Dry Eye Disease in Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Dry eye disease (DED) is the most common ocular surface disease, which severely affects the quality of life. An overall estimate of the prevalence, incidence, and risk factors of DED in Asia would help in planning and implementing appropriate public health strategies. OBJECTIVES: The present study aimed to study the epidemiology of DED in Asia. METHODS: A comprehensive and systematic search was performed using several databases, including PubMed, Cochrane Library, and Web of Science, in January 2021. A random-effects meta-analysis was performed on logit-transformed prevalence and incidence rates to calculate pooled prevalence and incidence estimates. Meta-regression and subgroup analyses were performed to explain the heterogeneity. RESULTS: Among the 6,742 articles identified, 23 were included in the analysis, with a total sample size of 1,488,935 subjects. Twenty studies reported the prevalence of DED in Asia, two studies reported the incidence, and one study reported both prevalence and incidence. The estimated pooled prevalence of DED in any population in Asia was 20.1% (95% confidence interval [Ozdemir et al., Acta Ophthalmol. 2019;97(1):e91-6]: 13.9-28.3%), and the incidence 16.7% (95% CI: 0-34.9%). The prevalence rate of DED in males and females was 16.4% (95% CI: 10.0-25.8%) and 21.7% (95% CI: 14.7-30.8%; p < 0.001), respectively. In general, the prevalence increased with age. The risk factors considered for specific populations were not significant, and the prevalence in the general population, excluding the populations considered at risk, was similar at 20.9% (95% CI: 12.8-32.1%). CONCLUSIONS: DED is common in Asian populations and causes a significant disease burden. Its prevalence is higher in females than that in males, and it tends to increase in severity with age. Further research on additional risk factors is needed to adequately explain the epidemiology of DED in Asia.

Iguratimod Attenuates Macrophage Polarization and Antibody-Mediated Rejection After Renal Transplant by Regulating KLF4.

Background: This study aimed to explore the effect and mechanism of iguratimod (IGT) on M1 macrophage polarization and antibody-mediated rejection (ABMR) after renal transplant. Methods: Bioinformatics analysis was performed using three public databases derived from the GEO database. Sprague-Dawley (SD) rats were pre-sensitized with donors of Wistar rats in skin transplantation and a rat renal transplant ABMR model was established from the donors to skin pre-sensitized recipients. Subsequently, IGT was treated on the ABMR model. Routine staining and immunofluorescence (IF) staining were performed to observe the pathological changes in each group and flow cytometry was performed to detect the changes of DSA titers in peripheral blood. In addition, bone-marrow-derived macrophage (BMDM) was extracted and interfered with IGT to explore the effect of IGT in vivo. PCR, IF staining, and Western blot were used to detect the expression of related genes and proteins. Results: Bioinformatics analysis revealed that several immune cells were significantly infiltrated in the ABMR allograft, while M1 macrophage was noticed with the most significance. Results of IF staining and PCR proved the findings of the bioinformatics analysis. Based on this, IGT was observed to significantly attenuate the degree of peritubular capillary vasculitis and arteriolitis in the rat renal transplant ABMR model, whereas it decreases the expression of C4d and reduces the titer of DSA. Results in vitro suggested that M1 macrophage-related transcripts and proteins were significantly reduced by the treatment of IGT in a dose- and time-dependent manner. Furthermore, IGT intervention could remarkably decrease the expression of KLF4. Conclusion: Polarization of M1 macrophages may aggravate ABMR after renal transplant by promoting DSA-mediated endothelial cell injury, and IGT may attenuate the pathogenesis of ABMR by targeting KLF4.