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Xu Cao, Qiu-Ling Fan Department of Nephrology, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Qiu-Ling FanDepartment of Nephrology, The First Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang 110001, People’s Republic of ChinaTel +86 13904012680Email cmufql@163.comAim: More than half of microRNAs are located in genes. LncRNAs are host genes of intronic microRNAs that regulate intracellular splicing to form pre-miRNAs that are processed to mature miRNAs. MicroRNAs work as partners or antagonists of their host lncRNAs by fine-tuning their target genes. However, whether lncRNA-MIR503HG (miR-503 host gene) is co-transcribed with miR-503 and affects miR-503 splicing, thereby affecting its target gene Bcl-2 expression and cell mitochondrial apoptotic pathway in diabetic nephropathy (DN) is currently unknown.Methods: Human proximal tubular (HK-2) cells cultured in high glucose were transfected with lncRNA MIR503HG overexpression/inhibition plasmid and miR-503 mimics/inhibitor. Real-time quantitative PCR was used to measure the expression levels of lncRNA MIR503HG, pre-miR-503, miR-503 and Bcl-2. Western blot was used to measure the protein expressions of Bcl-2, Bax, Cytc and cleaved-caspase 9/3. Annexin V/PI flow cytometry was used to measure apoptosis.Results: Host lncRNA MIR503HG was co-transcribed with miR-503. MIR503HG regulated the expression of miR-503 by affecting miR-503 splicing synthesis. In the presence of high glucose, the expression levels of lncRNA MIR503HG and miR-503 were up-regulated in HK-2 cells cultured in high glucose. Bcl-2 expression was inhibited and levels of apoptosis-related proteins Cytc and Bax were increased in HK-2 cells cultured in high glucose, all of which promoted the caspase cascade reaction, leading to increased caspase-9 and caspase-3 shear fragments inducing apoptosis of the mitochondrial pathway. Inhibition of MIR503HG led to a reduction in miR-503 expression, up-regulated its target gene Bcl-2, inhibited the expression levels of Bax and other apoptosis-related proteins and attenuated HK-2 cell apoptosis induced by high glucose. Co-transfection of miRNA-503 partially offset the effect of MIR503HG-siRNA.Conclusion: MIR503HG indirectly regulates Bcl-2 by promoting the co-transcription of miRNA-503 to participate high-glucose-induced proximal tubular cell apoptosis, providing a new target for diabetic nephropathy treatment.Keywords: diabetic nephropathy, lncRNA MIR503HG, miR-503, host gene, apoptosis

Si Wen,1,* Zhao-Hua Wang,2,* Cong-Xiao Zhang,1 Ying Yang,1 Qiu-Ling Fan1 1Department of Nephrology, First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Affiliated Dalian Friendship Hospital of Dalian Medical University, Dalian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiu-Ling FanDepartment of Nephrology, First Hospital of China Medical University, No. 155 Nanjing Bei Street, Shenyang 110001, People’s Republic of ChinaTel +86 13904012680Email cmufql@163.comBackground: Apoptosis has been repeatedly linked with diabetic kidney disease (DKD), which is a programmed cell death mediated by effector caspases-3, 6 and 7, targeting > 600 substrates. However, the pathophysiologic correlations of this process remain obscure. As a putative tumor suppressor, gasdermin E (GSDME) was recently reported to be cleaved by caspase-3 to produce a GSDME-N fragment which targets the plasma membrane to switch apoptosis to secondary necrosis. However, it remains elusive whether GSDME is involved in the regulation of DKD.Methods: To evaluate the therapeutic potential of caspase-3 inhibition in DKD, we administered caspase-3 inhibitor Z-DEVD-FMK to STZ-induced diabetic mice for eight weeks. Albuminuria, renal function, pathological changes, and indicators of secondary necrosis and fibrosis were evaluated. In vitro, human tubule epithelial cells (HK-2 cells) were subjected to high-glucose treatment. Secondary necrosis was determined by LDH release, GSDME cleavage, and morphological feature under confocal microscopy. Z-DEVD-FMK and GSDME inhibition by shRNA were administered to suppress the cleavage and expression of GSDME. Flow cytometry, cytotoxicity assay and immunoblot were used to assess cell death and fibrogenesis.Results: Caspase-3 inhibition by Z-DEVD-FMK ameliorated albuminuria, renal function, and tubulointerstitial fibrosis in diabetic mice. The nephroprotection mediated by Z-DEVD-FMK was potentially associated with inhibition of GSDME. In vitro, molecular and morphological features of secondary necrosis were observed in glucose-stressed HK-2 cells, evidenced by active GSDME cleavage, ballooning of the cell membrane, and release of cellular contents. Here we showed that caspase-3 inhibition prevented GSDME activation and cell death in glucose-treated tubular cells. Specifically, knocking down GSDME directly inhibited secondary necrosis and fibrogenesis.Conclusion: These data suggest GSDME-dependent secondary necrosis plays a crucial role in renal injury, and provides a new insight into the pathogenesis of DKD and a promising target for its treatment.Keywords: GSDME, DFNA5, secondary necrosis, diabetic kidney disease, Z-DEVD-FMK

Tian-Kui Ma,1,* Li Xu,1,2,* Ling-Xu Lu,1,3,* Xu Cao,1 Xin Li,1 Lu-Lu Li,1 Xu Wang,4 Qiu-Ling Fan1 1Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Clinical Laboratories, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3The First Respiratory Department, General Hospital of Fushun Mining Bureau, Fushun, Liaoning, People’s Republic of China; 4Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiu-Ling Fan Email cmufql@163.comPurpose: This study aimed to investigate whether ursolic acid (UA) mitigates renal inflammation, oxidative stress and fibrosis by regulating the angiotensin II type 1 receptor-associated protein (ARAP1)/angiotensin II type 1 receptor (AT1R) signaling pathway and subsequently alleviating renal damage.Methods: db/db mice were divided randomly into a diabetic nephropathy (DN) group and a UA treatment group. Light microscopy and electron microscopy were used to observe pathological changes in renal tissues. Immunohistochemistry (IHC) was employed to examine changes in the expression of ARAP1, AT1R, 8-hydroxydeoxyguanosine (8-OHdG), NADPH oxidase 2 (NOX2), the extracellular matrix protein fibronectin (FN), IL-1β and IL-18 in renal tissues. Western blotting and RT-qPCR were used to detect the respective changes in the protein and mRNA levels of ARAP1, AT1R, NOX4, NOX2, transforming growth factor-β1 (TGF-β1), FN, collagen IV, IL-1β and IL-18 in renal tissues and mesangial cells. In addition, immunofluorescence staining was employed to examine changes in FN and NOX2 expression in mesangial cells.Results: UA treatment effectively reduced the body weights and blood glucose levels of db/db mice (p

Background: Despite previous studies suggesting that developmental care can provide benign stimulation to promote neural development of newborns, more evidence is needed regarding the other clinical benefits of developmental care., Objective: To evaluate the effect of implementing developmental care on the length of hospital stay, the improvement of care practice in neonatal intensive care units, as well as the short-term outcome of very low birth weight infants., Design: Cluster-randomized controlled trial., Setting(s) and Participants: From March 1, 2021 to March 1, 2022, 1400 very low birth weight infants were recruited from 14 tertiary neonatal intensive care units in China., Methods: We assigned 14 neonatal intensive care units to either developmental care or standard care. The length of hospital stay of the infants was the primary outcome analyzed at the individual level. Secondary outcomes were family centered care practice including parental involvement, the skin to skin care, exclusive breast milk, oral immune therapy and breastfeeding. The environmental management (noise and light) and the short-term outcomes were also evaluated., Results: The length of hospital stay for the developmental care group was 65 % as long as that for the control group (HR: 0.65, 95 % CI, 0.451-0936, p = 0.021). After controlling the covariables, the adjusted HR = 0.755 (95 % CI, 0.515 to 1.107, p = 0.150). When compared to the control group, the developmental care group had greater access to SSC, with 22 infants (3.8 %) in the developmental care group compared to 13 infants (1.7 %) in the standard care group (p = 0.013). A greater proportion of infants in the developmental care group were fed at the breast, than those in the standard care group (136 [23.6 %] vs 9 [1.1 %]; p = 0.029). Compared to the control group, exclusively breast milk was significantly more favorable in the developmental care group (435 [75.6 %] vs 114 [15.0 %]; p = 0.001). The difference remained significant even after adjusting for covariates. However, the rate of oral immune therapy and parental involvement was similar in the two groups. The average noise and light levels in the developmental care group were significantly lower than those in the standard care group. After adjusting for confounders, the difference remained significant. There were no significant differences among groups in the mortality and major morbidity., Conclusions: Developmental care might have developed an accumulated effect over time on the length of hospital stay among very low birth weight infants. The implementation of developmental care can greatly improve family centered care practices and the neonatal intensive care unit environment., Registration: ClinicalTrials.govNCT05166720. Registration date: 1 March, 2021., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: This study explores the efficacy of electroacupuncture (EA) in treating cerebral palsy (CP) in Sprague-Dawley (SD) pups, specifically CP animal models, and its molecular mechanisms., Methods: Gait analysis and Y-maze were used to detect the improvement of motor ability and cognitive function of CP rats after EA treatment. Transcription sequencing was used to determine the key pathway for EA to improve the symptoms of CP. PPAR agonists were used to verify the causal relationship between the pathway and the improvement of CP phenotype., Results: The motor ability and cognitive function of CP pups were improved after EA treatment. The results of transcriptome sequencing suggest that the improvement of CP phenotype may be caused by the activation of PPAR pathway. PPAR pathway is widely activated in the epithelium of CP pups treated with EA, which is verified by qPCR. Rosiglitazone (Ros), a PPAR agonist, can improve CP phenotype while activating PPAR pathway, which proves the causal relationship between PPAR pathway activation and CP phenotype improvement., Conclusion: Our study demonstrated behavioral improvements and enhanced cognitive functions in CP models after EA treatment by activating PPAR pathway, suggesting new perspectives for CP rehabilitation, and providing theoretical support for acupuncture treatment of CP., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Diabetic Kidney Disease (DKD) is a complex disease associated with circadian rhythm and biological clock regulation disorders. Melatonin (MT) is considered a hormone with renal protective effects, but its mechanism of action in DKD is unclear., Methods: We used the GSE151325 dataset from the GEO database for differential gene analysis and further explored related genes and pathways through GO and KEGG analysis and PPI network analysis. Additionally, this study used a type 2 diabetes db/db mouse model and investigated the role of melatonin in DKD and its relationship with clock genes through immunohistochemistry, Western blot, real-time PCR, ELISA, chromatin immunoprecipitation (ChIP), dual-luciferase reporter technology, and liposome transfection technology to study DEC1 siRNA., Results: Bioinformatics analysis revealed the central position of clock genes such as CLOCK, DEC1, Bhlhe41, CRY1, and RORB in DKD. Their interaction with key inflammatory regulators may reveal melatonin's potential mechanism in treating diabetic kidney disease. Further experimental results showed that melatonin significantly improved the renal pathological changes in db/db mice, reduced body weight and blood sugar, regulated clock genes in renal tissue, and downregulated the TLR2/MyD88/NF-κB signaling pathway. We found that the transcription factor DEC1 can bind to the TLR2 promoter and activate its transcription, while CLOCK's effect is unclear. Liposome transfection experiments further confirmed the effect of DEC1 on the TLR2/MyD88/NF-κB signaling pathway., Conclusion: Melatonin shows significant renal protective effects by regulating clock genes and downregulating the TLR2/MyD88/NF-κB signaling pathway. The transcription factor DEC1 may become a key regulatory factor for renal inflammation and fibrosis by activating TLR2 promoter transcription. These findings provide new perspectives and directions for the potential application of melatonin in DKD treatment., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

This study was conducted to clarify the long-term effects of biochar application on the structure and function of the fungal community in continuous cropping watermelon soil. Taking watermelon root soil as the research object, Illumina NovaSeq high-throughput sequencing and FUNGuild platform were used to analyze the differences in soil fungal community composition, diversity, and function after 3-year biochar additions of 7.5, 15.0, and 30.0 t·hm -2 and to explore the correlation between soil environmental factors and fungal community structure under the control of biochar. The results showed that compared to that in the absence of biochar (control), the soil pH, available phosphorus, available potassium, total nitrogen, organic matter, and cation exchange capacity increased, but available nitrogen decreased with biochar addition. High-throughput sequencing results showed that biochar amendment improved the fungal community structure in continuous cropping watermelon soil and increased the richness and diversity of soil fungi. A total of 922 OTU were obtained from all soil samples, and the species annotation results indicated that the dominant fungal groups were Ascomycota, Basidiomycota, Mortierellomycota, Chytridiomycota, and Glomeromycota, with these phyla accounting for 85.70 %-92.45 % of the total sequences.The relative abundance of Ascomycota and Basidiomycota decreased, whereas the abundance of Mortierellomycota and Glomeromycota increased with biochar addition.At the genus level, the application of biochar increased the relative abundance of Mortierella and Rhizophlyctis but decreased the abundance of Fusarium . The Mantel test showed that soil available potassium, available nitrogen, organic matter, and pH were the main environmental factors leading to the shift in the soil fungal community composition.The functional prediction with FUNGuild showed that the many nutrient types among the different treatments were saprotrophic, pathotrophic, and symbiotrophic. The relative abundance of pathotrophs significantly decreased, but the abundance of symbiotrophs significantly increased with the medium and high doses of biochar treatment. In conclusion, the application of biochar changed the soil physicochemical properties, promoted the development of soil fungal community structure and functional groups in a healthy and beneficial direction, and improved the quality of continuous cropping watermelon soil.

Aims: Several studies have reported dietary microorganisms' beneficial effects on human health. We aimed to detect the potential association between dietary live microbe intake and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 1999 to 2018., Methods: According to the Sanders classification system of dietary live microbes, the study participants were divided into three groups: low, medium, and high live microbe groups. In patients with T2DM, DKD was assessed by glomerular filtration rate (< 60 mL/min/1.73 m 2 using the Chronic Kidney Disease Epidemiology Collaboration algorithm), proteinuria (urinary albumin to creatinine ratio ≥ 30 mg/g), or both. Weighted univariate and multivariate logistic regression and subgroup analyses were conducted to investigate the independent association between dietary live microbe and DKD., Results: The study included 3836 participants, of whom 1467 (38.24%) had DKD for the diagnosis. Our study demonstrated that participants in the high dietary live microbe group were more likely to be older, female, non-Hispanic White, have higher education levels, have a lower prevalence of smoking, have a high poverty-income ratio, have higher energy intake, lower haemoglobin (HbA1c) and serum creatinine levels, and lower risk of progression. After adjustment for covariates, patients in the high dietary live microbe group had a low prevalence of DKD, whereas no significant association with DKD was found between the medium and low dietary live microbe groups. No statistically significant interaction was observed in all subgroup analyses except for HbA1c (p for interaction < 0.05)., Conclusions: Our results indicate that high dietary live microbe intake was associated with a low DKD prevalence., (© 2024. The Author(s).)

The aim of this study was to investigate the effects of positive anti-thyroid peroxidase (TPO) antibodies on fertility, embryo quality, and pregnancy outcomes in women with normal thyroid function. A cross-sectional study of 1223 infertile women who received assisted reproductive technology (ART) treatment for the first time was conducted at our hospital from January 2019 to March 2022. Overall, 263 infertile women were included, comprising 263 cycles and 1813 embryos, and were divided into a positive group and a control group based on TPO antibody levels. The positive group was further divided into two subgroups according to the median antibody titer, and the therapeutic indices and pregnancy outcomes for each group were compared. The results showed that the AMH level in the positive group was significantly lower than that in the control group (2.37 (1.26-3.63) ng/ml vs. 3.54 (1.74-5.41) ng/ml, p  < 0.001). The high-quality embryo rate (40.04% vs. 45.49%, p  = 0.034) and live birth rate (23.26% vs. 36.16, p  = 0.035) of the positive group were lower than those of the control group; the miscarriage rate was higher than that of the control group (37.50% vs. 17.95%, p  = 0.035). The live birth rate in the low-titer group was significantly higher than that in the high-titer group (32.56% vs. 13.95%, p  = 0.041). Studies have shown that positive anti-thyroid peroxidase antibodies are associated with a decreased ovarian reserve and decreased embryo quality. High titers of anti-thyroid peroxidase antibodies can reduce the live birth rate.

Objectives : There is growing evidence that antioxidant-rich diets protect against chronic kidney disease (CKD). However, the relationship between the Composite Dietary Antioxidant Index (CDAI), an important measure of an antioxidant diet, and CKD has received little attention. Therefore, here we investigated the relationship between the CDAI and CKD through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2011-2018 data. Methods : The CDAI was calculated based on the intake of six dietary antioxidants. A survey-based multivariate linear regression analysis was performed to analyze the independent relationship between the CDAI and CKD. Weighted multivariate regression and subgroup analyses were conducted to explore the relationship between the CDAI and CKD. Results : A total of 6874 NHANES participants represented 181.9 million non-institutionalized US residents (mean age, 46.43 ± 0.38 years; 49.87% female; 40.62% non-Hispanic white; 20.24% non-Hispanic black; and 13.94% Mexican American). The weighted linear regression model with full adjustment for confounding variables was -0.0155 (-0.0417, 0.0107) for Q2 ( P for trend <0.0001), -0.0052 (-0.0346, 0.0242) for Q3 ( P for trend <0.0001), and -0.0305 (-0.0491, -0.0120) for Q4 ( P for trend = 0.0094) upon comparison with the lowest quartile of the CDAI. None of the interactions in any subgroup analysis were statistically significant except for individuals with a history of diabetes or the aged population (≥60 years) ( P for interaction <0.05). Conclusions : The CDAI was positively associated with a lower prevalence of CKD in adults in the United States. Further large-scale prospective studies are required to analyze the role of the CDAI in CKD.

Tubulointerstitial abnormalities contribute to the progression of diabetic kidney disease (DKD). However, the underlying mechanism of the pathobiology of tubulointerstitial disease is largely unknown. Here, we showed that MYCT1 expression was downregulated in in vitro and in vivo DKD models. Adeno-associated virus (AAV)-Myct1 significantly attenuated renal dysfunction and tubulointerstitial fibrosis in diabetic db/db mice and downregulated Sp1 transcription and TGF-β1/SMAD3 pathway activation. In human proximal tubular epithelial cells, high glucose-induced high expression of SP1 and TGF-β1/SMAD3 pathway activation as well as overaccumulation of extracellular matrix (ECM) were abrogated by MYCT1 overexpression. Mechanistically, the binding of VDR to the MYCT1 promoter was predicted and confirmed using dual-luciferase reporter and ChIP analysis. VDR transcriptionally upregulates MYCT1. Our data reveal MYCT1 as a new and potential therapeutic target in treating DKD., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

This study investigated the effects of dietary isoleucine (Ile) on growth performance, intestinal expression of amino acid transporters, protein metabolism-related genes and intestinal microbiota in starter phase Chinese yellow-feathered chickens. Female Xinguang yellow-feathered chickens (n = 1,080, aged 1 d) were randomly distributed to 6 treatments, each with 6 replicates of 30 birds. Chickens were fed diets with 6 levels of total Ile (6.8, 7.6, 8.4, 9.2, 10.0, and 10.8 g/kg) for 30 d. The average daily gain and feed conversion ratio were improved with dietary Ile levels (P < 0.05). Plasma uric acid content and glutamic-oxalacetic transaminase activity were linearly and quadratically decreased with increasing dietary Ile inclusion (P < 0.05). Dietary Ile level had a linear (P < 0.05) or quadratic (P < 0.05) effect on the jejunal expression of ribosomal protein S6 kinase B1 and eukaryotic translation initiation factor 4E binding protein 1. The relative expression of jejunal 20S proteasome subunit C2 and ileal muscle ring finger-containing protein 1 decreased linearly (P < 0.05) and quadratically (P < 0.05) with increasing dietary Ile levels. Dietary Ile level had a linear (P = 0.069) or quadratic (P < 0.05) effect on the gene expression of solute carrier family 15 member 1 in jejunum and solute carrier family 7 member 1 in ileum. In addition, bacterial 16S rDNA full-length sequencing showed that dietary Ile increased the cecal abundances of the Firmicutes phylum, and Blautia, Lactobacillus, and unclassified&#95;Lachnospiraceae genera, while decreased that of Proteobacteria, Alistipes, and Shigella. Dietary Ile levels affected growth performance and modulated gut microbiota in yellow-feathered chickens. The appropriate level of dietary Ile can upregulate the expression of intestinal protein synthesis-related protein kinase genes and concomitantly inhibit the expression of proteolysis-related cathepsin genes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to the higher birth rate of preterm infants and improvements in their management, metabolic bone disease of prematurity (MBDP) has a high incidence and is attracting attention. However, clear indicators for the early diagnosis of MBDP are lacking. We aimed to explore simple and feasible early warning indicators for diagnosing MBDP. Our study collected case data of premature infants from two medical centers in Chongqing from January 2020 to February 2022. According to the inclusion and exclusion criteria, data from 136 cases were collected. The correlation between 14 variables in each case and the occurrence of MBDP was analyzed. According to area under the receiver operating characteristic curve (AUROC) analysis, the best cutoff value for each variable was determined. Potential predictors were selected, and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to establish the association of two models with MBDP, whose results were used to develop a diagnostic nomogram. Furthermore, a model decision curve was analyzed. Four predictors were selected from 14 clinical variables by LASSO regression, and Model I was established, including the following characteristics: height (>36 cm), head circumference (≤29.49 cm), total serum calcium (Ca) (>2.13 mmol/L), and alkaline phosphatase (ALP) (>344 U/L) levels. A single predictor, the ALP level (>344 U/L), was used to establish Model II. The AUROC values of the two models were 0.959 for Model I and 0.929 for Model II. In conclusion, in this study, two diagnostic models of MBDP were developed using four combinations of predictors and ALP as a single predictor. Both models showed good sensitivity and specificity for the early diagnosis of metabolic bone disease (MBD), and an ALP level of 344 U/L was defined as a simple and effective diagnostic threshold. In future studies, using larger samples, diagnostic threshold values of ALP for premature infants of different ages should be established, and internal and external validations are needed to improve the adaptability of the current model., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Dimeric pyruvate kinase (PK) M2 (PKM2) plays an important role in promoting the accumulation of hypoxia-inducible factor (HIF)-1α, mediating aberrant glycolysis and inducing fibrosis in diabetic kidney disease (DKD). The aim of this work was to dissect a novel regulatory mechanism of Yin and Yang 1 (YY1) on lncRNA-ARAP1-AS2/ARAP1 to regulate EGFR/PKM2/HIF-1α pathway and glycolysis in DKD. Materials and methods: We used adeno-associated virus (AAV)-ARAP1 shRNA to knocked down ARAP1 in diabetic mice and overexpressed or knocked down YY1, ARAP1-AS2 and ARAP1 expression in human glomerular mesangial cells. Gene levels were assessed by Western blotting, RT-qPCR, immunofluorescence staining and immunohistochemistry. Molecular interactions were determined by RNA pull-down, co-immunoprecipitation, ubiquitination assay and dual-luciferase reporter analysis. Results: YY1, ARAP1-AS2, ARAP1, HIF-1α, glycolysis and fibrosis genes expressions were upregulated and ARAP1 knockdown could inhibit dimeric PKM2 expression and partly restore tetrameric PKM2 formation, while downregulate HIF-1α accumulation and aberrant glycolysis and fibrosis in in-vivo and in-vitro DKD models. ARAP1 knockdown attenuates renal injury and renal dysfunction in diabetic mice. ARAP1 maintains EGFR overactivation in-vivo and in-vitro DKD models. Mechanistically, YY1 transcriptionally upregulates ARAP1-AS2 and indirectly regulates ARAP1 and subsequently promotes EGFR activation, HIF-1α accumulation and aberrant glycolysis and fibrosis. Conclusion: Our results first highlight the role of the novel regulatory mechanism of YY1 on ARAP1-AS2 and ARAP1 in promoting aberrant glycolysis and fibrosis by EGFR/PKM2/HIF-1α pathway in DKD and provide potential therapeutic strategies for DKD treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Ma, Wang, Zhang, Liu, Liu, Huang, Zhu, Zhang, Yin, Xu, Ding, Liu, Shi and Fan.)

Ferroptosis plays an important role in ischemia-reperfusion (I/R)-induced cardiac injury and there are many defects in current targeted delivery of miRNAs for the treatment of ferroptosis. We herein report a unique hydrogel (Gel) that can be triggered by a near-infrared-II (NIR-II) light with deep tissue penetration and biocompatible maximum permissible exposure (MPE) value for in situ treatment after I/R. The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Using 1064 nm light irradiation, local microenvironment photothermal-triggered on-demand noninvasive controllable delivery of miRNA was achieved, aiming to inhibit I/R-induced ferroptosis. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in I/R model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The aim of this study is to apply a Mendelian randomization (MR) design to investigate the potential causal associations between the body mass index (BMI), body fat mass such as trunk fat mass and waist circumference (WC), and diabetic kidney disease (DKD). A two-sample MR study was conducted to obtain exposure and outcome data from previously published studies. The instrumental variables for BMI, trunk fat mass, and WC were selected from genome-wide association study datasets based on summary-level statistics. The random-effects inverse-variance weighted (IVW) method was used for the main analyses, and the weighted median and MR-Egger approaches were complementary. In total, three MR methods suggested that genetically predicted BMI, trunk fat mass, and WC were positively associated with DKD. Using IVW, we found evidence of causal relationships between BMI [odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.47-2.69; p = 7.89 × 10 -6 ], trunk fat mass (OR = 1.80; 95% CI, 1.28-2.53; p = 6.84 × 10 -4 ), WC (OR = 2.48; 95% CI, 1.40-4.42; p = 1.93 × 10 -3 ), and DKD. MR-Egger and weighted median regression also showed directionally similar estimates. Both funnel plots and MR-Egger intercepts showed no directional pleiotropic effects involving the aforementioned variables and DKD. Our MR analysis supported the causal effect of BMI, trunk fat mass, and WC on DKD. Individuals can substantially reduce DKD risk by reducing body fat mass and modifying their body fat distribution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Li, Mei, Huang, Liu, Zhu, Ma and Fan.)

The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.

The plateau is a special environment with low air pressure and low oxygen content. The average altitude of Qinghai-Tibet is 3,500 m, and the atmospheric oxygen partial pressure in most areas is lower than 60% of that at sea level. In order to adapt to the plateau low-oxygen environment, the human body has developed corresponding physiological structure and functions adjust. In the present review, the regulation mechanism of cerebral blood flow (CBF) under high-altitude environments was elaborated in eight aspects: the arterial blood gas, endogenous substances in the nerve and blood, the cerebral neovascularization, the hematocrit, cerebral auto-regulation mechanism, cerebrovascular reactivity, pulmonary vasoconstriction, and sympathetic automatic regulation, aiming to further explore the characteristics of changes in brain tissue and cerebral blood flow in a hypoxic environment.

Objective: Alkaline phosphatase (ALP) is a ubiquitous enzyme in humans that can be used for diagnosing childhood diseases. Infants have the highest rapid growth rate and are susceptible to metabolic bone diseases. In infants, ALP activities exhibit significant month-wise variations, and authoritative standards are lacking. The present study aimed to provide a reference for the diagnosis of diseases related to abnormal ALP activities in infants., Methods: This study included 24,618 samples collected from infants aged 0-12 months from three medical centers in Chongqing, China. Samples of infants diagnosed with diseases that may affect ALP activity have been exclude. ALP activity was analyzed using an automatic biochemical analyzer. A percentile curve for ALP activity in male and female infants was constructed using MATLAB, and the skewness-median-coefficient of variation method was employed for curve fitting., Results: ALP activity in male and female infants peaked at 0-4 months; the peak appeared at 1-2 months and declined gradually thereafter. After 4-5 months of age, the ALP activities declined further, with the lowest values observed at 11-12 months of age. A comparison between the data from this study and a those from a published German study indicates that Chinese infants exhibited peak ALP activity later and subsequent decline greater than German infants., Conclusions: A percentile curve was constructed for month-wise ALP activity in male and female infants, which could provide a reference for diagnosing diseases related to abnormal ALP activity in infants., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To investigate the protective effects of Zuogui Wan (ZGW) on bone loss induced by ovariectomy (OVX) and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model., Methods: Fifty Sprague-Dawley female rats were randomly divided into sham-operated (sham) group and four OVX subgroups. Rats subjected to sham and OVX were treated with the vehicle (OVX, 1 mL/100 g weight, n = 10), 17β-estradiol (E2, 50 μg*kg-1*d-1), and ZGW at the doses of 2.3 (ZGW-L) and 4.6 (ZGW-H) g/kg/day lyophilized powder daily for 3 months, respectively. The serum biochemical parameters of 17β-estrogen (17β-E2), tartrate-resistant acid phosphatase (TRACP-5b) and bone alkaline phosphatase (BALP) were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones. Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur. The gene or protein expression of orexin-A, orexin receptor 1 (OX1R), orexin receptor 2 (OX2R), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were assayed by either quantitative polymerase chain reaction or Western blot analysis., Results: Compared with the OVX group, ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and17β-E2 (P < 0.01). Meanwhile, ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number, and arranging the trabeculae structure properly. Compared with the OVX group, it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae, and OPG in the tibiae of ZGW groups (P < 0.01, < 0.05), while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae (P < 0.01)., Conclusion: ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.

Background: This study aimed to evaluate the correlation and consistency between traditional head measurement and structured light three-dimensional (3D) scanning parameters when measuring infant skull shape., Methods: A total of 76 infants aged 3 months to 2.5 years old were included in the study. Head circumference (HC) was measured with a tape measure. The transverse, anteroposterior, and oblique diameters were measured using a spreading caliper, and the cranial vault asymmetry index (CVAI) and a cranial index (CI) of symmetry were calculated; 76 cases were measured successfully. The above indexes were measured using a structured light 3D scanning system (71 cases were measured with success). Thus, in the end, the valid data of 71 cases were analyzed, and the measurements of the two approaches were compared., Results: The 95% confidence interval of traditional head measurement and structured light 3D scanning was between 0.633 and 0.988. Pearson's correlation coefficient indicated a high correlation between the two methods (r=0.793-0.980). The correlation coefficients of the transverse diameter, anteroposterior diameter, and HC, and the CI of symmetry were higher than 0.9. The lowest correlation coefficient for the CVAI was 0.793. The P values of the above measurement data were all <0.001, which indicated that they were closely related. A Bland-Altman plot indicated reasonable consistency between the two methods., Conclusions: Both traditional head measurement and structured light 3D scanning are suitable for the measurement of infant head shape. However, while traditional head measurement using a spreading caliper is economical and simple, making it suitable for general screening at a basic level, structured light 3D scanning can deliver additional parameters, which is useful for infants with an abnormal head shape. The latter is also convenient for designing a customized helmet for skull correction when needed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tp-21-186). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Objective: The U-shaped association between serum uric acid (SUA) and the functional outcome has been found in acute ischemic stroke (AIS). However, it is unclear if SUA is associated with red blood cell morphology in AIS. This study aimed to determine the relationship between SUA and red blood cell distribution width (RDW) in patients with AIS. Methods: A cross-sectional study including 438 consecutive patients with AIS was conducted. SUA and RDW, biochemical parameters that reflect the heterogeneity of red blood cell volume, were evaluated on admission. We evaluated the association between SUA and RDW through linear curve fitting analyses and two-piecewise regression analyses. Results: The association between SUA levels and RDW followed a U-shape in all patients. In females, the values of RDW significantly decreased with the increment of SUA (per mg/dl: β, -1.45; 95% CI: -2.15 to -0.75; p < 0.001) in patients with SUA <3.86 mg/dl and increased with the increment of SUA (per mg/dl: β, 0.60; 95% CI: 0.22-0.97; p = 0.002) in patients with SUA ≥ 3.86 mg/dl. Similar results were observed in males with the turning point of SUA = 4.82 mg/dl. After adjusting for potential confounders, a U-shaped association between SUA and RDW was maintained in females, but no statistical significance was maintained in patients with SUA ≥ 4.82 mg/dl in males ( p = 0.206). Conclusion: In the sample of patients with AIS, we found a U-shaped relationship between SUA levels and RDW, with the turning point of SUA (3.96 mg/dl in females and 4.82 mg/dl in males) by the threshold effect analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rong, Zhao, Yang, Fan, Zhang, Han, Cai and Zhu.)

1. This experiment was conducted to evaluate the effects of dietary isoleucine (Ile) on reproductive performance and certain indices of metabolism and oxidative stress in Chinese yellow-feathered broiler breeder hens.2. A total of 600, 40-week-old Chinese yellow-feathered broiler breeder hens were fed a basal diet formulated with maize, corn gluten meal and spray-dried blood cell meal containing 3.3 g/kg Ile, or supplemented to contain 4.5, 5.7, 6.9, or 8.1 g/kg Ile for five weeks. Each dietary treatment had six replicates with 20 birds per replicate. After three weeks of receiving the trial diets, 24 eggs were collected at random from each replicate to measure egg quality. Starting after four weeks of treatment, 50 settable eggs per replicate were collected for 7 d in succession for hatching. After five weeks of being fed the treatment diets, birds were slaughtered for tissue and organ collection.3. For the overall period, laying rate, egg weight, egg mass and hatchling weight linearly (P < 0.05) and quadratically (P < 0.05) increased with dietary Ile levels. Final body weight, feed intake and relative liver weight of birds fed 3.3 g/kg Ile was lower compared to birds fed the other diets (P < 0.05). There was no effect of Ile level on egg quality (P > 0.05). Hatchling weight was linearly (P < 0.05) and quadratically increased (P < 0.05) in line with dietary supplemental Ile.4. After three weeks on the trial diets, birds fed the diet containing 3.3 g/kg Ile had decreased blood TG concentrations compared to breeders fed 6.9 or 8.1 g/kg Ile (P < 0.05). Activities of CK were significantly higher in breeders fed the 3.3 g/kg Ile diet compared to all other levels of dietary Ile after five weeks of treatment. A quadratic effect (P < 0.05) was evident for glucose at 8.1 g/kg Ile level. After five weeks of treatment, plasma TG concentrations in birds fed 3.3 g/kg Ile were significantly lower than in birds fed all other levels of Ile. Glucose concentrations in breeder hens receiving the 3.3 g/kg Ile diet were lowest and the highest concentrations were in birds fed 5.7 g/kg Ile (P < 0.05). Plasma activities of LDH were highest in breeders on the 3.3 g/kg Ile diet but were only significantly different (P < 0.05) for birds fed 5.7 g/kg Ile.5. The current study indicated that Ile deficiency decreased reproductive performance and appeared to serve as a stressor. The optimal dietary Ile for Chinese yellow-feathered broiler breeder hens in the laying period was 5.79 g/kg feed (0.75 g/d).

Calcium (Ca) and non-phytate phosphorus (NPP) are fundamental minerals for bone formation and growth, and optimizing their level is required in broiler production. This experiment was conducted to investigate the effect and interaction of dietary Ca and NPP on growth performance, tibial characteristics and biochemical variables for slow-growing yellow-feathered broilers during 1-28 d (the starter phase). Seven hundred and twenty hatchling female broilers were randomly divided into nine groups, which received three levels of Ca (0.80%, 0.90%, 1.00%) each with three levels of NPP (0.40%, 0.45%, 0.50%). The results showed: (1) Dietary Ca level influenced (P < 0.05) the feed to gain ratio (F:G) and average daily feed intake (ADFI). Compared with broilers provided 1.00% Ca, ADFI of birds provided with 0.80% or 0.90% Ca and F:G of those with 0.90% Ca were decreased (P < 0.05). Dietary NPP level did not affect (P > 0.05) growth performance of broilers. (2) Dietary Ca affected (P < 0.05) tibial length. Compared with birds provided with 0.80% Ca, the length of tibia was decreased (P < 0.05) in birds received 1.00% Ca. Interactions between dietary Ca and NPP were observed (P < 0.05) on ash content, breaking strength and bone density of tibia. These three characteristics were better when birds received 0.90% Ca and 0.40% NPP or 1.00% Ca and 0.45% NPP. (3) Dietary Ca significantly affected (P < 0.05) the activity of alkaline phosphatase (ALP) in serum with decreased activity in birds fed 0.80% or 0.90% Ca. The dietary NPP influenced (P < 0.05) the contents of Ca in serum. Serum Ca was increased when birds were provided 0.40% NPP compared with other levels (P < 0.05). Again, there was interaction between Ca and NPP in diet on the contents of phosphorus (P) in serum (P < 0.05). In conclusion, interactions occurred between dietary Ca and NPP level on tibial breaking strength, density, ash content, and the content of P in the serum of young yellow-feathered broilers. Furthermore, dietary Ca affected ADFI, F:G and serum ALP activity, and dietary NPP also affected the P content in serum. Considering all indicators, 0.90% Ca and 0.40% NPP are optimal for slow-growing yellow-feathered broilers during 1-28 d of age., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for ischemic stroke; however, whether LDL-C affects the platelet deformation function in the peripheral blood circulation in patients with acute ischemic stroke (AIS) is unknown. The present study aimed to investigate the relationship between LDL-C and platelet distribution width (PDW) in AIS patients. Methods: We conducted a cross-sectional hospitalized-based study of consecutive 438 patients with AIS within 24 h. Blood samples were collected upon admission and prior to drug administration, and LDL-C and PDW (a parameter that reflects the heterogeneity of platelet volume) were assessed. The relationship between LDL-C and PDW were analyzed by linear curve fitting analyses. Crude and adjusted beta coefficients of LDL-C for PDW with 95% confidence intervals were analyzed using multivariate-adjusted linear regression models. Results: The PDW was significantly higher in the high LDL-C group compared with those in the normal LDL-C group (16.28 ± 0.37 fl vs. 16.08 ± 0.37 fl, p < 0.001). Adjusted smoothed plots suggested that there are linear relationships between LDL-C and PDW, and the Pearson's correlation coefficient (95%) was 0.387 (0.304-0.464, p < 0.001). The beta coefficients (95% CI) between LDL-C and PDW were 0.15 (0.12-0.18, p < 0.001) and 0.14 (0.11-0.18, p < 0.001), respectively, in AIS patients before and after adjusting for potential confounders. Conclusion: Our study suggested that the elevated LDL-C level was related to increased PDW among AIS patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yuan, Cai, Zhao, Zhao, Hong, Ding, Yang, Fan, Zhu, Zhou, Li, Zhu and Guan.)

This study investigated the effects of dietary Arginine (Arg) on performance, intestinal antioxidative capacity, immunity, and gut microbiota in Chinese yellow-feathered chickens. One thousand two hundred 1-day-old female Qingyuan partridge chickens were randomly assigned to 5 groups with 6 replicates of 40 birds each. Chickens were fed diets with 5 levels of total Arg (8.5, 9.7, 10.9, 12.1, and 13.3 g/kg) without antibiotics for 30 d. The ADFI, ADG, and feed conversion ratio were improved with dietary Arg levels (P < 0.05). The proportions of CD3 + and CD4 + /CD8 + lymphocytes responded in a linear (P < 0.05) manner and those of CD4 + in a linear or quadratic (P < 0.05) manner as dietary Arg levels increased. Dietary Arg level had a linear (P < 0.05) or quadratic (P < 0.05) effect on the gene expression of glutathione peroxidase 1, heme oxygenase 1, nuclear factor erythroid 2-related factor 2, and the activities of glutathione peroxidase and total antioxidative capacity in the jejunum and ileum. The relative expression of IL-1β, myeloid differentiation primary response 88, and Toll-like receptor 4 decreased linearly (P < 0.05) in the ileum with increasing dietary Arg levels; secretory IgA contents were increased. In addition, sequencing data of 16S rRNA indicated that dietary Arg increased the relative abundance of Firmicutes phylum, Romboutsia and Candidatus Arthromitus genera, while decreased that of Clostridium sensu stricto 1. A diet containing 12.1 g Arg/kg promoted growth performance, intestinal antioxidation, and innate immunity and modulated gut microbiota in yellow-feathered chickens., (Copyright © 2020. Published by Elsevier Inc.)

The meat quality of chicken is an important factor affecting the consumer's health. It was hypothesized that n-3 polyunsaturated fatty acid (n-3 PUFA) could be effectively deposited in chicken, by incorporating antioxidation of soybean isoflavone (SI), which led to improved quality of chicken meat for good health of human beings. Effects of partial or complete dietary substitution of lard (LA) with linseed oil (LO), with or without SI on growth performance, biochemical indicators, meat quality, fatty acid profiles, lipid-related health indicators and gene expression of breast muscle were examined in chickens. A total of 900 males were fed a corn-soybean meal diet supplemented with 4% LA, 2% LA + 2% LO and 4% LO and the latter two including 30 mg SI/kg (2% LA + 2% LO + SI and 4% LO + SI) from 29 to 66 days of age; each of the five dietary treatments included six replicates of 30 birds. Compared with the 4% LA diet, dietary 4% LO significantly increased the feed efficiency and had no negative effect on objective indices related to meat quality; LO significantly decreased plasma triglycerides and total cholesterol (TCH); abdominal fat percentage was significantly decreased in birds fed the 4% LO and 4% LO + SI diets. Chickens with LO diets resulted in higher contents of α-linolenic acid (C18:3n-3), EPA (C20:5n-3) and total n-3 PUFA, together with a lower content of palmitic acid (C16:0), lignoceric acid (C24:0), saturated fatty acids and n-6:n-3 ratio in breast muscle compared to 4% LA diet (P < 0.05); they also significantly decreased atherogenic index, thrombogenic index and increased the hypocholesterolemic to hypercholesterolemic ratio. Adding SI to the LO diets enhanced the contents of EPA and DHA (C22:6n-3), plasma total superoxide dismutase, reduced glutathione (GSH)/oxidized glutathione and muscle GSH content, while decreased plasma total triglyceride and TCH and malondialdehyde content in plasma and breast muscle compared to its absence (P < 0.05). Expression in breast muscle of fatty acid desaturase 1 (FADS1), FADS2, elongase 2 (ELOVL2) and ELOVL5 genes were significantly higher with the LO diets including SI than with the 4% LA diet. Significant interactions existed between LO level and inclusion of SI on EPA and TCH contents. These findings indicate that diet supplemented with LO combined with SI is an effective alternative when optimizing the nutritional value of chicken meat for human consumers.

The persistent transactivation of epidermal growth factor receptor (EGFR) causes subsequent activation of the TGF-β/Smad3 pathway, which is closely associated with fibrosis and cell proliferation in diabetic nephropathy (DN), but the exact mechanism of persistent EGFR transactivation in DN remains unclear. ARAP1, a susceptibility gene for type 2 diabetes, can regulate the endocytosis and ubiquitination of membrane receptors, but the effect of ARAP1 and its natural antisense long non-coding RNA (lncRNA), ARAP1-AS2, on the ubiquitination of EGFR in DN is not clear. In this study, we verified that the expression of ARAP1 and ARAP1-AS2 was significantly up-regulated in high glucose-induced human proximal tubular epithelial cells (HK-2 cells). Moreover, we found that overexpression or knockdown of ARAP1-AS2 could regulate fibrosis and HK-2 cell proliferation through EGFR/TGF-β/Smad3 signalling. RNA pulldown assays revealed that ARAP1-AS2 directly interacts with ARAP1. Coimmunoprecipitation, dual-immunofluorescence and ubiquitination assays showed that ARAP1 may maintain persistent EGFR activation by reducing EGFR ubiquitination through competing with Cbl for CIN85 binding. Taken together, our results suggest that the lncRNA ARAP1-AS2 may promote high glucose-induced proximal tubular cell injury via persistent EGFR/TGF-β/Smad3 pathway activation by interacting with ARAP1., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Cornelia de Lange syndrome (CdLS) is a genetic syndrome with severe neurodevelopmental disorders as the main manifestation. Its clinical manifestations included mental retardation, typical facial features, intrauterine and postnatal developmental delay, and deformity in multiple organs and systems, with an incidence rate of about 1/10000 to 1/30000. International CdLS Consensus Group was established in 2017 and issued the first international consensus on CdLS, i.e., "Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement", in July 2018. Being developed through a modified Delphi consensus process, this consensus provides guidance on the diagnosis and management of children with CdLS. This article gives an interpretation of this consensus, aiming to help clinicians with early identification, diagnosis, standard follow-up, and management of this disease.

Phenylethanol glycosides (CPhGs) are the core material basis of pharmacological activity in Cistanche tubulosa and have a variety of pharmacological effects. However, it is unclear whether CPhGs have an ameliorative effect on pressure overload-induced myocardial hypertrophy. In this study, male SD rats weighing (200 ± 20) g were established cardiac hypertrophy models by abdominal aortic coarctation (AAC). After operation, the rats were gavaged with corresponding medicine for 6 weeks (CPhGs 125, 250, and 500 mg/kg/d and valsartan 8.3 mg/kg/d). Echocardiography, heart weight index (HWI), cross-sectional area of cardiomyocytes (CSCA), fibrosis area, plasma endothelin 1(ET-1), and proinflammatory factors levels were detected. Our results showed that different CPhGs dosage decreased left ventricular posterior wall thickness (LVPWT), left ventricular end-diastolic diameter (LVED), HWI, CSCA, fibrosis area, ET-1, proinflammatory factors, arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin converting enzyme 1(ECE-1) mRNA levels, cyclooxygenase 2 (COX-2), high mobility group box 1 (HMGB-1) protein levels, and ECE-1 demethylation level while increasing left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-PKB), and phosphorylated endothelial nitric oxide synthetase (p-eNOS). The indexes of CPhGs 250 and 500 mg/kg group were significantly different from AAC group; compared with valsartan group (AV), the indexes of CPhGs 500 mg/kg group were not significantly different. In conclusion, CPhGs ameliorated myocardial hypertrophy rats by AAC, which may be related to ECE-1 demethylation inhibition and PI3K/PKB/eNOS enhancement., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Qiong-Ling Fan et al.)

The fatty acid composition of chicken's meat is largely influenced by dietary lipids, which are often used as supplements to increase dietary caloric density. The underlying key metabolites and pathways influenced by dietary oils remain poorly known in chickens. The objective of this study was to explore the underlying metabolic mechanisms of how diets supplemented with mixed or a single oil with distinct fatty acid composition influence the fatty acid profile in breast muscle of Qingyuan chickens. Birds were fed a corn-soybean meal diet supplemented with either soybean oil (control, CON) or equal amounts of mixed edible oils (MEO; soybean oil : lard : fish oil : coconut oil = 1 : 1 : 0.5 : 0.5) from 1 to 120 days of age. Growth performance and fatty acid composition of muscle lipids were analysed. LC-MS was applied to investigate the effects of CON v. MEO diets on lipid-related metabolites in the muscle of chickens at day 120. Compared with the CON diet, chickens fed the MEO diet had a lower feed conversion ratio (P < 0.05), higher proportions of lauric acid (C12:0), myristic acid (C14:0), palmitoleic acid (C16:1n-7), oleic acid (C18:1n-9), EPA (C20:5n-3) and DHA (C22:6n-3), and a lower linoleic acid (C18:2n-6) content in breast muscle (P < 0.05). Muscle metabolome profiling showed that the most differentially abundant metabolites are phospholipids, including phosphatidylcholines (PC) and phosphatidylethanolamines (PE), which enriched the glycerophospholipid metabolism (P < 0.05). These key differentially abundant metabolites - PC (14:0/20:4), PC (18:1/14:1), PC (18:0/14:1), PC (18:0/18:4), PC (20:0/18:4), PE (22:0/P-16:0), PE (24:0/20:5), PE (22:2/P-18:1), PE (24:0/18:4) - were closely associated with the contents of C12:0, C14:0, DHA and C18:2n-6 in muscle lipids (P < 0.05). The content of glutathione metabolite was higher with MEO than CON diet (P < 0.05). Based on these results, it can be concluded that the diet supplemented with MEO reduced the feed conversion ratio, enriched the content of n-3 fatty acids and modified the related metabolites (including PC, PE and glutathione) in breast muscle of chickens.

Objective: To study the effect of functional chewing training (FuCT) on masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy., Methods: A prospective study was performed for 48 children who were diagnosed with oral motor dysfunction from January 2019 to January 2020, and they were randomly divided into an FuCT group and an oral motor training group, with 24 children in each group. Both groups received FuCT or oral motor training for 12 weeks, and then they were evaluated in terms of the changes in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling., Results: There were no significant differences between the two groups in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling before treatment (P>0.05). After the 12-week training, the FuCT group showed significant improvements in the masticatory function and the severity of tongue thrust and drooling (P<0.05), but with no improvement in the frequency of drooling (P>0.05), while the oral motor training group had no improvements in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling (P>0.05). After the 12-week training, the FuCT group had more significantly improvements in the severity of tongue thrust and the severity and frequency of drooling than the oral motor training group (P<0.05)., Conclusions: FuCT can effectively improve the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy.

Elevated red blood cell distribution width (RDW) has been found to be associated with the occurrence of ischemic stroke. However, there is no defined relationship between RDW and neuronal damage in acute ischemic stroke (AIS). This study was designed to determine the relationship between RDW and neuronal damage in AIS patients. A total of 442 consecutive AIS patients from January 2018 to June 2019 were evaluated for neuronal damage, which was estimated by serum neuron-specific enolase (NSE) levels. Red blood cell distribution width-standard deviation (RDW-SD), a parameter that reflects the heterogeneity of red blood cell volume, was also assessed. We evaluated the association between the RDW-SD and serum NSE level through multivariate-adjusted linear regression analysis. Both the serum NSE level and the incidence of high NSE increased according to the increased RDW-SD tertile in AIS patients ( p <0.01). There was a positive correlation between RDW-SD and serum NSE levels ( r =0.275, 95% CI: 0.187-0.359, p <0.001). The beta coefficients (95% CI) between RDW-SD and serum NSE levels were 0.32 (0.21-0.42, p <0.001) and 0.26 (0.15-0.38, p <0.001), respectively, in AIS patients before and after adjusting for potential confounders. In conclusion, we found a significant positive association between RDW-SD and neuronal damage in AIS patients.

Machine learning shows enormous potential in facilitating decision-making regarding kidney diseases. With the development of data preservation and processing, as well as the advancement of machine learning algorithms, machine learning is expected to make remarkable breakthroughs in nephrology. Machine learning models have yielded many preliminaries to moderate and several excellent achievements in the fields, including analysis of renal pathological images, diagnosis and prognosis of chronic kidney diseases and acute kidney injury, as well as management of dialysis treatments. However, it is just scratching the surface of the field; at the same time, machine learning and its applications in renal diseases are facing a number of challenges. In this review, we discuss the application status, challenges and future prospects of machine learning in nephrology to help people further understand and improve the capacity for prediction, detection, and care quality in kidney diseases.

Objective: To compare the therapeutic effect of thunder-fire moxibustion combined with vibration training and simple vibration training on low back pain of primary osteoporosis by Young 's modulus of ultrasonic wave, and seek an objective evaluating method., Methods: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. The patients in the two groups were treated with vibration training using whole body vibration treatment bed. In the observation group, thunder-fire moxibustion was applied at Yaoyangguan (GV 3), Mingmen (GV 4), Ganshu (BL 18), Shenshu (BL 23) and Dachangshu (BL 25). The treatment was given once every other day, 3 times a week for 4 weeks. The visual analogue score (VAS), real-time shear wave elastography (RTSWE) and medical outcomes study 36-item short-form hearth survey (SF-36) were used to evaluate pain intensity, multifidus muscle tone ( Young 's modulus) and quality of life before treatment, after 4-week treatment and 1 month after treatment., Results: Compared before treatment, the VAS scores, Young 's modulus of multifidus muscle and 5 dimensions of SF-36 (physical condition, body pain, general health, social function and mental health) after 4-week treatment and 1 month after treatment were significantly improved in the two groups (all P <0.05), the physiological role in the observation group after 4-week treatment and 1 month after treatment were improved (both P <0.05). In the observation group, the VAS scores, Young 's modulus of multifidus muscle and 3 dimensions of SF-36 (physiological role, body pain and general health) after 4-week treatment and 1 month after treatment were superior to the control group (all P <0.05)., Conclusion: The therapeutic effect of thunder-fire moxibustion combined with vibration training is superior to simple vibration training in relieving low back pain intensity and multifidus muscle tone, and improving quality of life for primary osteoporosis. RTSWE technique can be an objective examination method to evaluate pain.

Sodium and chloride are the key factors maintaining normal osmotic pressure (OSM) and volume of the extracellular fluid, and influencing the acid-base balance of body fluids. The experiment was conducted to investigate the effects of dietary Na+ and Cl- level on growth performance, excreta moisture, blood biochemical parameters, intestinal Na+-glucose transporter 1 (SGLT1) messenger RNA (mRNA), and Na+-H+ exchanger 2 (NHE2) mRNA, and to estimate the optimal dietary sodium and chlorine level for yellow-feathered chickens from 22 to 42days. A total of 900 22-day-old Lingnan yellow-feathered male chickens were randomly allotted to five treatments, each of which included six replicates of 30 chickens per floor pen. The basal control diet was based on corn and soybean meal (without added NaCl and NaHCO3). Treatments 2 to 5 consisted of the basal diet supplemented with equal weights of Na+ and Cl-, constituting 0.1%, 0.2%, 0.3% and 0.4% of the diets. Supplemental dietary Na+ and Cl- improved the growth performance (P<0.05). Average daily gain (ADG) showed a quadratic broken-line regression to increasing dietary Na+ and Cl- (R2=0.979, P<0.001), and reached a plateau at 0.1%. Supplemental Na+ and Cl- increased (P<0.05) serum Na+ and OSM in serum and showed a quadratic broken-line regression (R2=0.997, P=0.004) at 0.11%. However, supplemental Na+ and Cl- decreased (P<0.05) serum levels of K+, glucose (GLU) and triglyceride. Higher levels of Na+and Cl- decreased duodenal NHE2 transcripts (P<0.05), but had no effect on ileal SGLT1 transcripts. The activity of Na+ /K+-ATPase in the duodenum decreased (P<0.05) with higher levels of dietary Na+ and Cl-. In conclusion, the optimal dietary Na+ and Cl- requirements for yellow-feathered chickens in the grower phase, from 22 to 42 days of age, to optimize ADG, serum Na+, OSM, K+ and GLU were 0.10%, 0.11%, 0.11%,0.17% and 0.16%, respectively, by regression analysis.

This study evaluated the optimal concentrations of dietary ME and CP for the productivity, reproductive performance, and fat deposition in laying duck breeders aged from 29 to 45 wk. Using a 3 × 3 factorial arrangement of treatments, 648 Longyan laying duck breeders with similar BW were randomly assigned to experimental diets of 2,600 (HME = high ME), 2,500 (MME = medium ME), or 2,400 (LME = low ME) kcal of ME/kg, each containing 19% (HCP = high CP), 18% (MCP = medium CP), or 17% (LCP = low CP) CP. Each dietary treatment contained 6 replicates of 12 birds each. Compared with birds fed the LCP diet, the egg production and egg mass were higher in birds fed HCP and MCP (P < 0.01), with better feed conversion (P < 0.01). Interactions were detected between ME and CP levels in egg production, egg mass, and feed conversion ratio as the LMEMCP diet was the best (P < 0.05). The birds fed MME (P < 0.05) had the lowest abdominal fat. The percentage of healthy ducklings was affected by maternal dietary CP (P < 0.05) with the HCP being the highest. The weight of large yellow follicles/ovarian weight was higher in birds fed HCP and MCP (P < 0.05), whereas the weight of small yellow follicles/ovarian weight was higher in birds fed HCP and LCP (P < 0.05). The hepatic transcript abundances of genes for very low density apolipoprotein-II and carnitine palmitoyltransferase-1A (CPT-1A) were lowest in birds fed MCP, whereas the highest abundance of CPT-1A transcripts was found in birds fed MME. These results revealed that the diets containing ME of 12.9 kcal/g protein optimized both egg production and egg mass, while the feed conversion was optimized at 12.8 kcal ME/g protein. Using ME to CP ratio of 12.9 kcal/g protein, i.e., 2,451 kcal ME/kg at 19% CP, maximized the reproductive performance and hatchling outcome of Longyan laying duck breeders., (© 2019 Poultry Science Association Inc.)

The human body is inhabited by a diverse microbial community that is collectively coined as commensal microbiota. Recent research has greatly advanced our understanding of how the commensal microbiota affects host health. Among the various kinds of pathogenic infections of the host, viral infections constitute one of the most serious public health problems worldwide. During the infection process, viruses may have substantial and intimate interactions with the commensal microbiota. A plethora of evidence suggests that the commensal microbiota regulates and is in turn regulated by invading viruses through diverse mechanisms, thereby having stimulatory or suppressive roles in viral infections. Furthermore, the integrity of the commensal microbiota can be disturbed by invading viruses, causing dysbiosis in the host and further influencing virus infectivity. In the present article, we discuss current insights into the regulation of viral infection by the commensal microbiota. We also draw attention to the disruption of microbiota homeostasis by several viruses.

Self-assembled hyaluronic acid (HA) nanoparticles have been extensively investigated as anticancer therapeutic agents due to the biocompatibility, biodegradability, and active targeting characteristics of HA. However, many HA nanoparticles are restricted to the applications in drug delivery for chemotherapy or lack effective imaging agents. Hence, we developed the camptothecin (CPT)-loaded HA-SS-BFVPBT nanoparticles (HSBNPs) as a multifunctional platform for two-photon imaging and synergistic chemo-photodynamic therapy at the same time. A novel conjugated oligomer photosensitizer, BFVPBT, which was conjugated onto HA through the redox-responsive disulfide linkage (SS), could not only provide a hydrophobic domain for the formation of nanoparticles and drug entrapment but also act as a two-photon photosensitizer that can be directly excited and simultaneously used in two-photon imaging and photodynamic therapy (PDT). HeLa cells overexpressing the HA receptor (CD44) were used for in vitro studies, which proved the specific cellular uptake of CPT-loaded HSBNPs and excellent two-photon PDT/chemotherapy synergistic effect. The nanoparticles have also been shown to realize tumor-targeting in vivo imaging in HeLa-tumor-bearing mice. Moreover, the fluorescence of CPT-loaded HSBNPs could be activated due to the degradation by the reductive glutathione (GSH) and overexpressed hyaluronidases (Hyal-1) in cancer cells, and the intracellular drug release rate was quickened, thus improving the probability of precise cancer diagnosis and therapy. Accordingly, this HSBNPs system is also anticipated to be a precise nanocarrier for other imaging and therapeutic agents besides CPT, offering a promising new avenue for imaging-guided efficient cancer therapy.

The evolution of organisms has provided a variety of mechanisms to maintain the integrity of its genome, but as damage occurs, DNA damage repair pathways are necessary to resolve errors. Among them, the DNA double-strand break repair pathway is highly conserved in eukaryotes, including mammals. Nonhomologous DNA end joining and homologous directed repair are two major DNA repair pathways that are synergistic or antagonistic. Clustered regularly interspaced short palindromic repeats genome editing techniques based on the nonhomologous DNA end joining repair pathway have been used to generate highly efficient insertions or deletions of variable-sized genes but are error-prone and inaccurate. By combining the homology-directed repair pathway with clustered regularly interspaced short palindromic repeats cleavage, more precise genome editing via insertion or deletion of the desired fragment can be performed. However, homologous directed repair is not efficient and needs further improvement. Here, we describe several ways to improve the efficiency of homologous directed repair by regulating the cell cycle, expressing key proteins involved in homologous recombination and selecting appropriate donor DNA.

A total of 200 one-day-old male broilers were assigned to five groups, and each group consisted of four replicates with 10 birds per replicate. Chicks were fed the basal diet with 0 (non-infected control), 0 (infected control), 10, 20, and 40 mg/kg soybean isoflavones (SI) for 42 days. At 21 days of age, chickens were inoculated with an infectious bursal dose (causing 50% morbidity) of the infectious bursal disease virus (IBDV) BC 6/85 strain by the eye-drop and nasal route (except for the non-infected group). Average daily gain (ADG) and average daily feed intake (ADFI) decreased ( p < 0.05) in broilers infected with infectious bursal disease virus (IBDV) from 22 to 42 days. However, infected broilers fed 10 and 20 mg SI/kg had the maximum ( p <0.05) ADG and ADFI from 1 to 42 days. Body weight (BW) increased ( p < 0.05) in infected broilers fed the 10 and 20 mg SI /kg diet. The bursa weight at 7 days post-infection (dpi) was increased ( p < 0.05) by the supplemental 10 mg SI/kg diet. Infected broilers showed the highest ( p < 0.05) bursa lesions, with an average score of 4.0 ± 0.0, while the severity of bursa lesions was decreased ( p < 0.05) at 3 dpi and 7 dpi by the supplemental 20 mg SI/kg diet. Supplemental SI at 20 mg/kg decreased ( p < 0.05) the viral protein 5 (VP5) mRNA expression at 3 dpi and 7 dpi. The level of interferon gamma (IFNγ) was elevated ( p < 0.05) in the infected group at 3 dpi and 7 dpi as compared with the control group, while its level was decreased (p < 0.05) by supplemental 10 mg/kg SI at 3 dpi. The level of nuclear factor κB in the bursal tissue showed the lowest value ( p < 0.05) with supplemental 10 and 20 mg SI/kg diet at 7 dpi. Supplemental 10, 20, 40 mg/kg SI improved ( p < 0.05) the serum total antioxidant activity (T-AOC) in infected broilers at 3 dpi. In addition, the serum level of malondialdehyde (MDA) decreased ( p < 0.05) in the group fed 20 mg/kg SI at 7 dpi. In conclusion, supplemental 10~20 mg/kg SI may have a positive effect on broiler chickens infected with IBDV, probably because SI decrease the severity of bursa lesions and viral protein 5 mRNA expression, and have strong antioxidant activity.

The study investigated whether different dietary energy and protein sources affect laying performance, antioxidant status, fresh yolk fatty acid profile and quality of salted yolks in laying ducks. In all, 360 19-week-old Longyan ducks were randomly assigned to four diets in a factorial arrangement (2×2). The four diets consisted of two energy sources, corn (CO) or sorghum (SO) and two protein sources, soybean meal (SM) and rapeseed meal with corn distillers dried grains with solubles (RMD), and each treatment contained six replicates of 15 birds each. The experimental diets were isocaloric (metabolizable energy, 10.84 MJ/kg) and isonitrogenous (CP, 17%). The results showed that egg production, average egg weight, egg mass and feed conversion ratio were not affected by diets (P>0.05). Plasma contents of reduced glutathione (GSH), GSH/oxidized glutathione and total antioxidant capacity were lower (P<0.05) in ducks fed the RMD diets compared with those fed SM diets with a substantial increase (P=0.006) in plasma content of malondialdehyde (MDA). Egg yolks from ducks fed SO diets had higher proportions of polyunsaturated fatty acids (PUFA) and lower saturated and monounsaturated fatty acids compared with CO diets (P<0.001). Similarly, ducks fed RMD diets had a higher content of PUFA and n-6/n-3 ratio in fresh yolks (P<0.001), and increased salted yolk MDA, carbonylated proteins content and incidence of hard salted yolks (P<0.05) compared with SM diets. Scanning electron microscopy showed that salted yolks contained rougher polyhedral granules and fewer fat droplets, and were surrounded with a layer of bunchy fibers in ducks fed SO+RMD than those fed CO+SM diet. In conclusion, the current study showed that feeding laying ducks with diets containing SO or RMD reduced antioxidant capacity and increased egg yolk concentrations of PUFA. It appeared that egg yolks from ducks fed these diets were more sensitive to lipid peroxidation and protein oxidation during salting, and reduced the quality of salted yolks.

The objective of this trial was to test the effects of oxidative stress induced by a high dosage of dietary iron on intestinal lesion and the microbiological compositions in caecum in Chinese Yellow broilers. A total of 450 1-day-old male chicks were randomly allotted into three groups. Supplemental iron (0, 700 and 1,400 mg/kg) was added to the basal diet resulting in three treatments containing 245, 908 and 1,651 mg/kg Fe (measured value) in diet respectively. Each treatment consisted of six replicate pens with 25 birds per pen. Jejunal enterocyte ultrastructure was observed by transmission electron microscopy. The results showed that a high dosage of dietary iron induced oxidative stress in broilers. Dilated endoplasmic reticulum (ER), autophagosome formation of jejunal enterocytes and decreased villi were caused by this oxidative stress. Compared to the control, concentration of the malondialdehyde (MDA) in jejunal mucosa in the 908 and 1,651 mg/kg Fe groups increased by 180% (p < .01) and 155% respectively (p < .01); activity of copper-zinc superoxide dismutase (Cu/ZnSOD) increased in jejunum (p < .01); and the concentration of plasma reduced glutathione (GSH) decreased by 34.9% (p < .01) in birds fed 1,651 mg/kg Fe. Gene expression of nuclear factor, erythroid-derived 2-like 2 (Nrf2) and zonula occludens-1 (ZO-1), in the higher dietary Fe groups was enhanced (p < .05). Species of microbial flora in caecum increased caused by oxidative stress. The PCR-DGGE (denaturing gradient gel electrophoresis) dendrograms revealed different microbiota (65% similarity coefficient) between the control and iron-supplemented groups (p < .05). These data suggest high dosage of iron supplement in feed diet can induce oxidative stress in Chinese Yellow broilers, and composition of microbiota in the caecum changed. It implied there should be no addition of excess iron when formulating diets in Chinese Yellow broilers., (© 2018 Blackwell Verlag GmbH.)

Contagious pustular dermatitis is an exanthematous zoonotic disease caused by the orf virus. Pandemic outbreaks of this disease cause great economic losses, while the pathogenesis of this disease still remains obscure. In this study, blood samples were collected from 628 asymptomatic goats across China for PCR-based virus detection. We detected the orf virus in the blood of asymptomatic goats. Moreover, the orf virus obtained from the blood of infected goats was infectious and induced typical symptoms of contagious pustular dermatitis after inoculation of uninfected dairy goats. In summary, our data provide evidence that asymptomatic animals may be carriers of orf virus. Our findings should contribute to elucidating the details underlying the pathogenesis of contagious pustular dermatitis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

BACKGROUND To investigate the protective effect of ursolic acid (UA) on high glucose (HG)-induced human glomerular mesangial cell injury and to determine whether UA inhibits cell proliferation and reactive oxygen species (ROS) production by suppressing PI3K/Akt/mTOR pathway activation. MATERIAL AND METHODS Human mesangial cells were cultured with normal glucose (NG group), high glucose (HG group), mannitol (mannitol hypertonic control group), or high glucose with different concentrations (0.5, 1.0, and 2.0 mmol/L) of UA (HG+UA groups). Cell proliferation and intracellular ROS levels were assessed by methyl thiazolyl tetrazolium (MTT) and dichloro-dihydro-fluorescein diacetate (DCFH-DA) flow cytometry assays, respectively. Western blotting was used to detect mesangial cell expression of PI3K/Akt/mTOR pathway components, including Akt, p-Akt, mTOR, and p-mTOR, and proteins related to cell injury, including TGF-β1 and fibronectin (FN). mRNA expression of TGF-β1 and FN were evaluated using real-time quantitative polymerase chain reaction (PCR). RESULTS Abnormal proliferation was observed in human glomerular mesangial cells at 48 h after treatment with HG, and UA suppressed the HG-induced proliferation of mesangial cells in a dose-dependent manner. UA inhibited ROS generation and oxidative stress in mesangial cells and mitigated mesangial cell injury. Treatment with UA reduced Akt and mTOR phosphorylation levels in mesangial cells exposed to HG (p<0.05 vs. HG) and downregulated protein and mRNA expression of TGF-β1 and FN in these cells (p<0.05 vs. HG). CONCLUSIONS UA attenuated mesangial cell proliferation and ROS generation by inhibiting HG-mediated PI3K/Akt/mTOR pathway activation, thereby ameliorating mesangial cell damage.

The study investigated the effects of increasing content of corn distillers' dried grains with solubles (DDGS) in the diets of laying ducks on oxidative status, laying performance, egg quality, and egg yolk fatty acid composition. Longyan females (1080) with similar BW at 17 wk of age were randomly assigned to 6 treatment groups, each consisting of 6 replicates of 30 birds. The basal diet (I) was a typical corn-soybean ration while the experimental diets (II to VI) substituted corn DDGS for soybean meal and wheat bran and a small reduction of corn. The level of substitution in diets (II to VI) was 6%, 12%, 18%, 24% and 30%. The experiment lasted for 18 wk. Average egg weight decreased linearly as the level of corn DDGS inclusion increased (P < 0.001). Haugh unit, albumen weight, and proportion declined as linear responses to corn DDGS substitution (P < 0.05), but yolk color linearly increased (P < 0.001); the proportions of oleic (C18:1) and total monounsaturated fatty acids in egg yolk linearly decreased with increasing corn DDGS and many of the key polyunsaturated fatty acids (PUFAs) like linoleic (C18:2n-6), arachidonic (C20:4n-6) and α-linolenic (C18:3n-3) acids linearly increased (P < 0.001), but not those of eicosapentaenoic (C20:5n-3) and docoshexaenoic (C22:6n-3) acids. The PUFAs n-6/n-3 ratio linearly increased with increasing corn DDGS level (P < 0.001). Increasing corn DDGS linearly increased hepatic expression of GPX1, HO-1, and Nrf2 and hepatic activity of GSH-Px and the liver content of MDA (P < 0.001). There were no treatment effects on egg production, egg mass, feed conversion ratio, eggshell thickness, strength, and yolk cholesterol content (P > 0.05). In conclusion, the current study indicates that the use of corn DDGS is possible as a replacement, primarily for soybean meal at levels up to 18% in the diets of laying ducks without affecting laying performance, egg quality, and antioxidant status. Increasing amounts of corn DDGS linearly increased egg yolk concentrations of key fatty acids like like C18:2n-6 and C18:3n-3 and the antioxidant enzyme activity of GSH-Px through the Nrf2 pathway to avoid oxidative stress., (© 2017 Poultry Science Association Inc.)

The study assessed the effects of different dietary levels of corn distillers dried grains with solubles (DDGS) on performance, oxidation status, intestinal immunity and meat quality in Chinese Yellow broilers aged from 1 to 63 days. Lingnan male hatchings (1440) were randomly assigned to six treatments, each consisting of six replicates of 40 birds. The basal diet (I) was a typical corn-soya bean ration while the experimental diets (II to VI) partially substituted corn DDGS for soya bean meal. The level of substitution in starter, grower and finisher diets was as follows: II, 2%, 4% then 6%; III, 4%, 8% then 12%; IV, 6%, 12% then 18%; V, 8%, 16% then 24%; VI, 10%, 20% then 30%. Average daily feed intake and feed-to-gain ratio increased as linear responses to corn DDGS substitution from 1 to 21 days (p < 0.001). The plasma content of triglycerides and liver content of malondialdehyde increased as linear responses to corn DDGS substitution (p < 0.05). There was a linear decrease (p < 0.001) in jejunal abundance of IL-6 transcripts, with a substantial reduction to approximately 25% those of broilers fed the control diet, and a quadratic effect existed for secretory immunoglobulin A (sIgA) (p < 0.001). In addition, increased dietary corn DDGS caused favourable changes in selected functional properties of the meat: drip loss at 24 and 96 h increased as linear response to corn DDGS substitution (p < 0.001). Further, meat colour L* values decreased and a* values increased linearly in response to increasing corn DDGS (p < 0.05). In conclusion, diet IV (6%, 12% then 18% corn DDGS) in Chinese Yellow broiler diets had no negative effects on performance, antioxidant capacity and meat quality. This level of inclusion also appeared to promote sIgA secretion and enhance anti-inflammatory status., (Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.)