Tracking investigation of archaeal composition and methanogenesis function from parental to offspring pigs.

Archaea play a crucial role in microbial systems, including driving biochemical reactions and affecting host health by producing methane through hydrogen. The study of swine gut archaea has a positive significance in reducing methane emissions and improving feed utilization efficiency. However, the development and functional changes of archaea in the pig intestines have been overlooked for a long time. In this study, 54 fecal samples were collected from 36 parental pigs (18 boars and 18 pregnant/lactating sows), and 108 fecal samples from 18 offspring pigs during lactation, nursery, growing, and finishing stages were tracked and collected for metagenomic sequencing. We obtained 14 archaeal non-redundant metagenome-assembled genomes (MAGs). These archaea were classified as Methanobacteriota and Thermoplasmatota at the phylum level, and Methanobrevibacter, Methanosphaera, MX-02, and UBA71 at the genus level, involving hydrogenotrophic, methylotrophic, and acetoclastic pathways. The hydrogenotrophic pathway dominated the methanogenesis function, and the vast majority of archaea participated in it. Dietary changes profoundly affected the archaeal composition and methanogenesis function in pigs. The abundance of hydrogen-producing bacteria in parental pigs fed high-fiber diets was higher than that in offspring pigs fed low-fiber diets. The methanogenesis function was positively correlated with fiber decomposition functions and negatively correlated with the starch decomposition function. Increased abundance of sulfate reductase and fumarate reductase, as well as decreased acetate/propionate ratio, indicated that the upregulation of alternative hydrogen uptake pathways competing with methanogens may be the reason for the reduced methanogenesis function. These findings contribute to providing information and direction in the pig industry for the development of strategies to reduce methane emissions, improve feed efficiency, and maintain intestinal health.

The study of routine laboratory factors in children with mycoplasma pneumoniae pneumonia: serum uric acid may have anti-inflammatory effect.

BACKGROUND: High uric acid levels are a risk factor for cardiovascular disorders, and metabolic diseases; however, the role of serum uric acid (sUA) during the mycoplasma pneumoniae pneumonia (MPP) of children is poorly known. This study aimed to clarify the effects of sUA during the MPP of children. METHODS: This was a prospective cohort study of children with MPP from multi-center inpatient departments from September 2019 to August 2020. Routine laboratory characteristics analyzed including ALT, AST, BUN, CREA, UA, LDH, CK-MB, WBC, N%, PLT, and CRP. Subjects were divided into 3 groups: non-MPP, mild MPP (MMPP), and severe MPP (SMPP). RESULTS: 949 subjects were enrolled, including 207 in non-MPP, 565 in MMPP, and 177 in SMPP. The optimal cutoff value for sUA is 239 µmmol/L in receiver operating characteristic (ROC) curves analysis. Multivariate logistic regression showed that WBC and sUA had significance for protective effects between non-MPP and SMPP, but CRP did not have significance between the two groups, N and PLT had significance for risk factors; WBC and sUA did not have significance for the protective effects between non-MPP and MMPP, CRP had significance between the two groups, N and PLT had significance for the risk effects. Similarly, binary logistic regression showed UA, WBC, and CRP had significance for the protective effects between non-MPP and MPP, but N and PLT had significance for the risk effects between the two groups. CONCLUSION: Both multivariate and binary logistic regression demonstrated that sUA displayed a protective effect during the MPP of children, which meant sUA is anti-inflammatory.

Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing.

Excessive expression of matrix metalloproteinase 9 (MMP-9) impedes healing of diabetic chronic wounds, thus wound dressing that could effectively inhibit the expression of MMP-9 offers significant clinical translation for diabetic wound healing. Herein, a hybrid hydrogel dressing was developed for localized and sustained delivery of MMP-9 siRNA (siMMP-9). siMMP-9 was complexed with Gly-TETA (GT), the GT/siMMP9 complex was then loaded into a thermosensitive hydrogel based on Pluronic F-127 (PF) and methylcellulose (MC). In vitro, this hybrid hydrogel dressing exhibited negligible cytotoxicity, prolonged the release of GT/siMMP-9 for up to 7 days, and significantly reduced MMP-9 expression. In vivo assessment in diabetic rats demonstrated that hydrogel provided localized and sustained delivery via the thermosensitive controlled release of entrapped GT/siMMP-9 into wound tissues for 7 days, resulting in dramatic MMP-9 silencing which significantly improved diabetic wound closure. This hybrid hydrogel dressing exhibited excellent biocompatibility, with no observed systemic toxicity in rats. Taken together, the hybrid hydrogel dressing may constitute an effective and biocompatible means of enhancing diabetic wound healing through effective silencing of the MMP-9 gene, and this hydrogel delivery system also offers a platform for in vivo delivery of siRNA for the treatment of other diseases.

Depletion of hepatic forkhead box O1 does not affect cholelithiasis in male and female mice.

Cholelithiasis is one of the most prevalent gastroenterological diseases and is characterized by the formation of gallstones in the gallbladder. Both clinical and preclinical data indicate that obesity, along with comorbidity insulin resistance, is a predisposing factor for cholelithiasis. Forkhead box O1 (FoxO1) is a key transcription factor that integrates insulin signaling with hepatic metabolism and becomes deregulated in the insulin-resistant liver, contributing to dyslipidemia in obesity. To gain mechanistic insights into how insulin resistance is linked to cholelithiasis, here we determined FoxO1's role in bile acid homeostasis and its contribution to cholelithiasis. We hypothesized that hepatic FoxO1 deregulation links insulin resistance to impaired bile acid metabolism and cholelithiasis. To address this hypothesis, we used the FoxO1LoxP/LoxP-Albumin-Cre system to generate liver-specific FoxO1-knockout mice. FoxO1-knockout mice and age- and sex-matched WT littermates were fed a lithogenic diet, and bile acid metabolism and gallstone formation were assessed in these animals. We showed that FoxO1 affected bile acid homeostasis by regulating hepatic expression of key enzymes in bile acid synthesis and in biliary cholesterol and phospholipid secretion. Furthermore, FoxO1 inhibited hepatic expression of the bile acid receptor farnesoid X receptor and thereby counteracted hepatic farnesoid X receptor signaling. Nonetheless, hepatic FoxO1 depletion neither affected the onset of gallstone disease nor impacted the disease progression, as FoxO1-knockout and control mice of both sexes had similar gallstone weights and incidence rates. These results argue against the notion that FoxO1 is a link between insulin resistance and cholelithiasis.

Hyperbranched cationic polysaccharide derivatives for efficient siRNA delivery and diabetic wound healing enhancement.

Gene vectors are important for successful siRNA delivery. Four types of hyperbranched cationic polysaccharide derivatives (HCP) were synthesized by conjuncting 1,2-ethylenediamine (EDA) and diethylenetriamine (DETA) with glycogen or amylopectin respectively and named as G-EDA, G-DETA, A-EDA and A-DETA. The efficiency and safety of these HCPs to deliver siRNA were explored in vitro and in vivo. Our results showed that HCPs could form complexes with siRNA. All HCP/siRNA exhibited negligible cytotoxicity. Compared with A-EDA and A-DETA, G-EDA and G-DETA could carry much more siRNA into cells and then escape from endosomes. The delivery of MMP-9 siRNA (siMMP-9) by G-EDA and G-DETA significantly inhibited MMP-9 in HaCaT cells. Wound models in diabetic rats demonstrated that treatment of G-EDA/siMMP-9 could potently knock down MMP-9 of skin wound tissues and then enhanced wound healing. In summary, this study provided an effective and safe approach for siRNA delivery in vitro and in vivo.

Naturally-occurring bacterial cellulose-hyperbranched cationic polysaccharide derivative/MMP-9 siRNA composite dressing for wound healing enhancement in diabetic rats.

The anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cells in vitro, while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats. STATEMENT OF SIGNIFICANCE: In this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats.

Ocular residual and corneal astigmatism in a clinical population of high school students.

PURPOSE: Total refractive astigmatism is usually the first consideration that guides the selection of contact lens type (e.g., spherical or toric), while the ocular source of the astigmatism is a second, but more important consideration, for the final clinical decision. This study was conducted to provide detailed data on this topic by evaluating astigmatic components in Chinese adolescents. METHODS: Participants were recruited from healthy high school students undergoing an annual ocular examination at a local hospital. Total astigmatism (TA), corneal astigmatism (CA), and ocular residual astigmatism (ORA) were determined by a Hartmann-Shack wavefront analyzer system (KR-1W, Topcon) with the natural pupil. The axis relationship between CA and ORA was placed into three categories: on-axis, defined as an axis with a difference of 0 ± 10°; opposite-axis, a difference of 90 ± 10°; and the rest defined as oblique-axis. RESULTS: The study consisted of 1,466 students (57.84% girls, age: 16.49 ± 1.05 years). ORA was present in 83.97%, 66.64%, and 45.23% of participants, according to the various criteria for astigmatism (≥ 0.50 D, ≥ 0.75 D, and ≥ 1.00 D, respectively). While with-the-rule was the most common axis orientation for both TA (76.28%) and CA (89.94%), against-the-rule predominated in ORA (93.82%; χ2 = 1688.544, p < 0.001). Opposite-axis was the major type of axis difference (90.96%) of clinical significance (i.e., ≥ 1.00 D) between CA and ORA, which also prevailed in all levels of TA (range: 56.25-82.26%). CONCLUSIONS: ORA is common in high school students and usually demonstrates a compensation relationship with CA, which should be taken into consideration when determining the design of contact lenses to correct refractive error.

Efficiency and Safety of ß-CD-(D3)7 as siRNA Carrier for Decreasing Matrix Metalloproteinase-9 Expression and Improving Wound Healing in Diabetic Rats.

Overexpression of matrix metalloproteinase-9 (MMP-9) is critical for diabetic chronic wounds involved in the refractory wound healing process. We aimed to develop a strategy through RNAi to decrease MMP-9 expression and improve diabetic wound healing. We had explored ß-CD-(D3)7 as a gene carrier to take siRNA and effectively interfere with MMP-9 expression. It has been proven that ß-CD-(D3)7 could be used as an effective siRNA delivery system. In this study, we want to know about the efficiency and safety of ß-CD-(D3)7/MMP-9 siRNA for improving wound healing in diabetic rats. ß-CD-(D3)7/MMP-9 siRNA treated animals show lower levels of MMP-9 expression, which induce faster wound-close rates. Histological evaluation indicates that ß-CD-(D3)7/MMP-9 siRNA significantly increases the content of collagen around the injured tissues. The number of neutrophilic ganulocytes was significantly decreased through treatment of ß-CD-(D3)7/MMP-9 siRNA. In vivo fluorescence imaging assessment shows that ß-CD-(D3)7/MMP-9 siRNA could not cause organ damage and organ accumulation. The results suggest that ß-CD-(D3)7/MMP-9 siRNA might be developed as a novel topical agent for the diabetic wounds treatment.

Antiasthmatic Effects of Eugenol in a Mouse Model of Allergic Asthma by Regulation of Vitamin D3 Upregulated Protein 1/NF-κB Pathway.

The aim of the study was to investigate the antiasthmatic effects of eugenol (EUG) and the possible mechanisms. Asthma model was established by ovalbumin induction. A total of 50 mice were randomly assigned to five experimental groups: control, OVA, OVA + dexamethasone (2 mg/kg), OVA + EUG (10 mg/kg), and OVA + EUG (20 mg/kg). Airway resistance (Raw) were measured, histological studies were evaluated by the hematoxylin and eosin (HE) staining, interleukin-4 (IL-4) and interleukin-5 (IL-5) were evaluated by enzyme-linked immunosorbent assay (ELISA), Vitamin D3 upregulated protein 1 (VDUP1), IκBα, P-IκBα, NF-κBP65, and p-NF-κBP65 were measured by Western blotting. Our study demonstrated that EUG inhibited OVA-induced increases in Raw and eosinophil count; IL-4 and IL-5 were recovered. Histological studies demonstrated that EUG substantially inhibited OVA-induced eosinophilia in the lung tissue. Western blotting studies demonstrated that EUG substantially inhibited P-IκBα, NF-κBP65, and p-NF-κBP65 protein levels and increased VDUP1 and IκBα protein levels. These findings suggest that EUG may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.