USP7 promotes cardiometabolic disorders and mitochondrial homeostasis dysfunction in diabetic mice via stabilizing PGC1ß.

Diabetic cardiomyopathy (DCM) is a major complication of diabetes and is characterized by left ventricular dysfunction. Currently, there is a lack of effective treatments for DCM. Ubiquitin-specific protease 7 (USP7) plays a key role in various diseases. However, whether USP7 is involved in DCM has not been established. In this study, we demonstrated that USP7 was upregulated in diabetic mouse hearts and NMCMs co-treated with HG+PA or H9c2 cells treated with PA. Abnormalities in diabetic heart morphology and function were reversed by USP7 silencing through conditional gene knockout or chemical inhibition. Proteomic analysis coupled with biochemical validation confirmed that PCG1ß was one of the direct protein substrates of USP7 and aggravated myocardial damage through coactivation of the PPARα signaling pathway. USP7 silencing restored the expression of fatty acid metabolism-related proteins and restored mitochondrial homeostasis by inhibiting mitochondrial fission and promoting fusion events. Similar effects were also observed in vitro. Our data demonstrated that USP7 promoted cardiometabolic metabolism disorders and mitochondrial homeostasis dysfunction via stabilizing PCG1ß and suggested that silencing USP7 may be a therapeutic strategy for DCM.

Hyperhomocysteinemia in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.

INTRODUCTION/AIMS: Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is an autosomal recessive disease chiefly caused by variants of ETFDH affecting fatty acid metabolism. In our cohort, hyperhomocysteinemia (HHcy) was common. In this study we aimed to identify the association between RR-MADD and HHcy. METHODS: We performed a retrospective review of 13 patients with RR-MADD. Thirty-three healthy controls were recruited, and logistic regression was used to investigate the association between RR-MADD and HHcy. Muscle tissues from six patients and six controls without myopathies were collected to measure the levels of flavin adenine dinucleotide (FAD), an active form of riboflavin. Whole-exome sequencing was performed to identify the disease-associated variants. RESULTS: The RR-MADD patients had a higher prevalence of HHcy (9 of 12) than controls (6 of 33, P < .001). In the multivariate analysis, RR-MADD was positively related to HHcy (P = .014). Muscular FAD levels were decreased in RR-MADD patients (P = .006). Thirteen variants (8 reported and 5 novel) were identified in ETFDH. Of these, c.250G > A was the most common pathogenic variant with an allelic frequency of 4 of 20. DISCUSSION: HHcy was associated with RR-MADD and may aid in the diagnosis of the disease. Our findings expand the mutational spectrum of RR-MADD.

Effect of maternal curcumin supplementation on intestinal damage and the gut microbiota in male mice offspring with intra-uterine growth retardation.

PURPOSE: The present study investigated whether maternal curcumin supplementation might protect against intra-uterine growth retardation (IUGR) induced intestinal damage and modulate gut microbiota in male mice offspring. METHODS: In total, 36 C57BL/6 mice (24 females and 12 males, 6-8 weeks old) were randomly divided into three groups based on the diet before and throughout pregnancy and lactation: (1) normal protein (19%), (2) low protein (8%), and (3) low protein (8%) + 600 mg kg-1 curcumin. Offspring were administered a control diet until postnatal day 35. RESULTS: Maternal curcumin supplementation could normalize the maternal protein deficiency-induced decrease in jejunal SOD activity (NP = 200.40 ± 10.58 U/mg protein; LP = 153.30 ± 5.51 U/mg protein; LPC = 185.40 ± 9.52 U/mg protein; P < 0.05) and T-AOC content (NP = 138.90 ± 17.51 U/mg protein; LP = 84.53 ± 5.42 U/mg protein; LPC = 99.73 ± 12.88 U/mg protein; P < 0.05) in the mice offspring. Maternal curcumin supplementation increased the maternal low protein diet-induced decline in the ratio of villus height-to-crypt depth (NP = 2.23 ± 0.19; LP = 1.90 ± 0.06; LPC = 2.56 ± 0.20; P < 0.05), the number of goblet cells (NP = 12.72 ± 1.16; LP = 7.04 ± 0.53; LPC = 13.10 ± 1.17; P < 0.05), and the ratio of PCNA-positive cells (NP = 13.59 ± 1.13%; LP = 2.42 ± 0.74%; LPC = 6.90 ± 0.96%; P < 0.05). It also reversed the maternal protein deficiency-induced increase of the body weight (NP = 13.00 ± 0.48 g; LP = 16.49 ± 0.75 g; LPC = 10.65 ± 1.12 g; P < 0.05), the serum glucose levels (NP = 5.32 ± 0.28 mmol/L; LP = 6.82 ± 0.33 mmol/L; LPC = 4.69 ± 0.35 mmol/L; P < 0.05), and the jejunal apoptotic index (NP = 6.50 ± 1.58%; LP = 10.65 ± 0.75%; LPC = 5.24 ± 0.71%; P < 0.05). Additionally, maternal curcumin supplementation enhanced the gene expression level of Nrf2 (NP = 1.00 ± 0.12; LP = 0.73 ± 0.10; LPC = 1.34 ± 0.12; P < 0.05), Sod2 (NP = 1.00 ± 0.04; LP = 0.85 ± 0.04; LPC = 1.04 ± 0.04; P < 0.05) and Ocln (NP = 1.00 ± 0.09; LP = 0.94 ± 0.10; LPC = 1.47 ± 0.09; P < 0.05) in the jejunum. Furthermore, maternal curcumin supplementation normalized the relative abundance of Lactobacillus (NP = 31.56 ± 6.19%; LP = 7.60 ± 2.33%; LPC = 17.79 ± 2.41%; P < 0.05) and Desulfovibrio (NP = 3.63 ± 0.93%; LP = 20.73 ± 3.96%; LPC = 13.96 ± 4.23%; P < 0.05), and the ratio of Firmicutes/Bacteroidota (NP = 2.84 ± 0.64; LP = 1.21 ± 0.30; LPC = 1.79 ± 0.15; P < 0.05). Moreover, Lactobacillus was positively correlated with the SOD activity, and it was negatively correlated with Il - 1ß expression (P < 0.05). Desulfovibrio was negatively correlated with the SOD activity and the jejunal expression of Sod1, Bcl - 2, Card11, and Zo - 1 (P < 0.05). CONCLUSIONS: Maternal curcumin supplementation could improve intestinal integrity, oxidative status, and gut microbiota in male mice offspring with IUGR.

Neuroinflammatory inhibition of synaptic long-term potentiation requires immunometabolic reprogramming of microglia.

Immunometabolism refers to the rearrangement of metabolic pathways in response to immune stimulation, and the ability of these metabolic pathways themselves to control immune functions. Many aspects of immunometabolism have been revealed through studies of peripheral immune cells. However, immunometabolic reprogramming of microglia, the resident immune cell of the central nervous system, and the consequential outcome on neuronal activity have remained difficult to unravel. Microglia are highly sensitive to subtle changes in their environment, limiting the techniques available to study their metabolic and inflammatory profiles. Here, using fluorescence lifetime imaging of endogenous NAD(P)H, we measure the metabolic activity of individual microglia within acute hippocampal slices. We observed an LPS-induced increase in aerobic glycolysis, which was blocked by the addition of 5 mM 2-deoxyglucose (2DG). This LPS-induced glycolysis in microglia was necessary for the stabilization of hypoxia inducible factor-1α (HIF-1α) and production of the proinflammatory cytokine, interleukin-1ß (IL-1ß). Upon release, IL-1ß acted via the neuronal interleukin-1 receptor to inhibit the formation of synaptic long-term potentiation (LTP) following high frequency stimulation. Remarkably, the addition of 2DG to blunt the microglial glycolytic increase also inhibited HIF-1α accumulation and IL-1ß production, and therefore rescued LTP in LPS-stimulated slices. Overall, these data reveal the importance of metabolic reprogramming in regulating microglial immune functions, with appreciable outcomes on cytokine release and neuronal activity.

An enhanced fluorescent probe through the strategy of using MgWO4 nanosheets to enhance terbium ion luminescence for highly sensitive and point-of-care visual quantitative testing of ciprofloxacin integrated with a low-cost smartphone-based platform.

In this work, MgWO4 nanosheets have been successfully synthesized by a simple hydrothermal method, and the morphology and composition of the MgWO4 nanosheets are characterized by SEM, TEM, XPS, and UV-vis. The results show that the as-prepared MgWO4 nanosheets have a triclinic symmetry phase and an obvious two-dimensional layered structure. Studies have shown that the MgWO4 semiconductor nanosheets can adjust the energy level, which significantly enhances the visible light absorption and the separation and transfer of photogenerated electrons, which facilitates the generation of photogenerated electrons. We use this feature to boost a terbium ion (Tb3+)-ciprofloxacin (CIP) system to enhance the luminescence, so as to achieve highly sensitive detection of CIP. The mechanism of Tb3+-MgWO4 for CIP detection is the effective energy transfer from WO42- in MgWO4 nanosheets to Tb3+-CIP, thereby enhancing the characteristic emission of Tb3+ and enhancing the sensitivity of CIP detection. The linear response of the Tb3+-MgWO4 enhanced fluorescent probe is in the range from 10 nM to 20 µM, and the detection limit (LOD) is 2 nM. In addition, we tested the recovery in spiked river water and mouse serum. Experiments have shown that the recovery of spiked samples is 97-102.2%, while the relative standard deviation (RSD) is less than 5.53%. The possible interfering substances in environmental samples will not interfere with the detection of CIP with the Tb3+-MgWO4 enhanced fluorescent probe. At the same time, the development of a smartphone-based portable device provides the possibility of CIP on-site detection. Our work provides a simple, fast, highly sensitive and stable method for detecting CIP in living organisms and the environment. Importantly, the strategy of MgWO4 nanosheet boosted terbium ion luminescence expands the application range of semiconductor nanomaterials.

A novel Q93H missense mutation in DCTN1 caused distal hereditary motor neuropathy type 7B and Perry syndrome from a Chinese family.

The Dynactin 1 (DCTN1) encodes the p150 subunit of dynactin, which engages retrograde axonal transport. Missense mutations in DCTN1 have been linked to a series of neurodegenerative diseases, including distal hereditary motor neuropathies (dHMN) and Perry syndrome. A few pathogenic DCTN1 mutations related with Perry syndrome have been described within, or adjacent to, the highly conserved N-terminal cytoskeleton-associated protein, glycine-rich (CAP-Gly) domain. But to our best knowledge, only the pathogenic G59S mutation in DCTN1 has been reported in dHMN7B families. Herein, we provided a novel heterozygous mutation in DCTN1 which caused both dHMN7B and Perry syndrome from a Chinese family. Whole exome sequencing (WES) was performed to identify the disease-associated genes. Single nucleotide variants (SNVs) and small insertions/deletions (INDELs) were further predicted with Mutation Taster, Polymorphism Phenotyping v2 (PolyPhen-2), and Sorting Intolerant From Tolerant (SIFT) and compared to the Single Nucleotide Polymorphism Database(dbSNP), Exome Aggregation Consortium (ExAC), and the 1000 Genomes Project. Furthermore, a novel missense mutation c.279G>C (Q93H) in DCTN1 was identified as the candidate loci. The mutation was confirmed with Sanger sequencing in the family members and cosegregated with various phenotypes. In silico analysis and molecular structural modeling, the mutation not only caused the loss of a hydrogen bond within the p150 protein but also affected the formation of hydrogen bonds between p150 and EB. Therefore, the new Q93H mutation in DCTN1 caused both familial dHMN7B and Perry syndrome. Our findings could expand the clinical and pathogenic spectrum and strengthen the clinical diagnostic role of the DCTN1 gene.

Maternal curcumin supplementation ameliorates placental function and fetal growth in mice with intrauterine growth retardation†.

Intrauterine growth retardation (IUGR) is a serious reproductive problem in humans. The objective of this study was to investigate the effects of daily maternal curcumin supplementation during pregnancy on placental function and fetal growth in a mouse model of IUGR fed the low-protein (LP) diet. Pregnant mice were divided into four groups: (1) normal protein (19% protein) diet (NP); (2) LP (8% protein) diet; (3) LP diet + 100 mg/kg curcumin (LPL); (4) LP diet +400 mg/kg curcumin (LPH). The results showed that the LP group decreased fetal weight, placental weight, placental efficiency, serum progesterone level, placental glutathione peroxidase activity activity, blood sinusoids area, and antioxidant gene expression of placenta. In addition, in comparison with the NP group, LP diet increased serum corticosterone level, placental malondialdehyde content, and apoptotic index. Daily curcumin administration decreased the placental apoptosis, while it increased placental efficiency, placental redox balance, blood sinusoids area, and antioxidant-related protein expression in fetal liver. The antioxidant gene expression of placenta and fetal liver was normalized to the NP level after curcumin administration. In conclusion, daily curcumin supplementation could improve maternal placental function and fetal growth in mice with IUGR.

SIRT2 modulates VEGFD-associated lymphangiogenesis by deacetylating EPAS1 in human head and neck cancer.

Sirtuin 2 (SIRT2) is one of seven mammalian homologs of silent information regulator 2 (Sir2) and an NAD+ -dependent deacetylase; however, its critical role in lymphangiogenesis remains to be explored. We investigate SIRT2 mediated regulation of vascular endothelial growth factor D (VEGFD) expression and lymphangiogenesis by deacetylating endothelial PAS domain protein 1 (EPAS1) in head and neck cancer (HNC) in vitro and in vivo. In this study, we report that SIRT2, rather than other members of the Sir2 family, reduces the expression of VEGFD and lymphangiogenesis in hypoxia-induced HNC cells and transplanted HNC mice models by reducing EPAS1 acetylation at Lys674 and decreasing the transcriptional activity of EPAS1 target genes. The expression of SIRT2 was closely related to the expression of VEGFD, lymphangiogenesis in subcutaneously transplanted mice models, and lymphangiogenesis in patients with HNC. Our results suggest that SIRT2 plays a central role in tumor lymphangiogenesis via deacetylating EPAS1 protein. Reagents targeting the NAD+ -dependent deacetylase activity of SIRT2 would be beneficial for inhibiting tumor lymphangiogenesis and treating other hypoxia-related diseases.

Development of a double monoclonal antibody-based sandwich enzyme-linked immunosorbent assay for detecting canine distemper virus.

Canine distemper virus (CDV) infection causes mass mortality in diverse carnivore species. For effective virus surveillance, rapid and sensitive assays are needed to detect CDV in field samples. In this study, after BABL/c mice were immunized with recombinant CDV-fusion (F) protein, monoclonal antibodies (mAbs) against recombinant CDV-F protein (designated 1A5, 1A6, and 7D5) were produced using traditional hybridoma cell technology. Next, capture antibody (1A6, 800 ng/well) and horseradish peroxidase (HRP)-conjugated detection antibody (HRP-7D5, 1:100, 500 ng/well) were used in a double monoclonal antibody-based sandwich enzyme-linked immunosorbent assay (ELISA) for CDV detection after optimization of both mAb amounts per well using a checkerboard titration test. Based on sandwich ELISA test results for 120 known CDV-negative samples, the cutoff value for a positive result was set to an OD450 nm value ≥ 0.196. As compared with test results obtained from commercial immune colloidal gold test strips, the low limits of detection for the two assays were revealed to be 100 TCID50 per 100 µL. In addition, the sandwich ELISA agreed 100% and 96.4% with commercial immune colloidal gold test strips when testing serum and stool samples. The sandwich ELISA assay provided statistically similar CDV detection. Thus, the sandwich ELISA developed here to detect CDV in fecal and serum samples provided good sensitivity, high specificity, and good reproducibility and should serve as an ideal method for large-scale surveillance of CDV infections in carnivores. KEY POINTS: • Three CDV mAbs that recognized different epitopes and bound to virion were generated. • The sandwich ELISA based mAbs to detect CDV in fecal and serum samples was developed. • The sandwich ELISA is an ideal method for detecting CDV infections in the field.

Curcumin attenuates insulin resistance and hepatic lipid accumulation in a rat model of intra-uterine growth restriction through insulin signalling pathway and sterol regulatory element binding proteins.

The objective of the present study was to investigate the effect of curcumin on insulin resistance (IR) and hepatic lipid accumulation in intra-uterine growth restriction (IUGR). Rats with a normal birth weight (NBW) or IUGR were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NBW-C and IUGR-C groups) from 6 to 12 weeks. Rats in the IUGR group showed higher levels of glucose and homeostasis model assessment for insulin resistance index (HOMA-IR) (P < 0·05) than in the NBW group. The livers of IUGR rats exhibited higher (P < 0·05) concentration of TAG and lower (P < 0·05) activities of lipolysis enzymes compared with the normal rats. In response to dietary curcumin supplementation, concentrations of serum insulin, glucose and HOMA-IR, pyruvate, TAG, total cholesterol and NEFA in the liver were decreased (P < 0·05). The concentrations of glycogen and activities of lipolysis enzymes in the liver were increased (P < 0·05) in the IUGR-C group compared with the IUGR group. These results were associated with lower (P < 0·05) phosphorylated insulin receptor substrate 1, protein kinase B or Akt, glycogen synthase kinase 3ß and expressions of sterol regulatory element binding protein 1 and fatty acid synthase (FASN); decreased expressions for Cd36, sterol regulatory element binding protein 1c (Srebf1) and Fasn; increased (P < 0·05) expression of PPARα; and expressions for Ppara and hormone-sensitive lipase in the liver of IUGR-C rats than the IUGR rats. Maternal malnutrition caused IR and lipid accumulation in the liver. Curcumin supplementation prevented IR by regulating insulin signalling pathways and attenuated hepatic lipid accumulation.

Nanobody-horseradish peroxidase fusion protein as an ultrasensitive probe to detect antibodies against Newcastle disease virus in the immunoassay.

BACKGROUND: Sensitive and specific antibodies can be used as essential probes to develop competitive enzyme-linked immunosorbent assay (cELISA). However, traditional antibodies are difficult to produce, only available in limited quantities, and ineffective as enzymatic labels. Nanobodies, which are single-domain antibodies (sdAbs), offer an alternative, more promising tool to circumvent these limitations. In the present work, a cELISA using nanobody-horseradish peroxidase (HRP) fusion protein firstly designed as a probe was developed for detecting anti-Newcastle disease virus (NDV) antibodies in chicken sera. RESULTS: In the study, a platform for the rapid and simple production of nanobody-HRP fusion protein was constructed. First, a total of 9 anti-NDV-NP protein nanobodies were screened from a immunised Bactrian camel. Then, the Nb5-HRP fusions were produced with the platform and used for the first time as sensitive reagents for developing cELISA to detect anti-NDV antibodies. The cut-off value of the cELISA was 18%, and the sensitivity and specificity were respectively 100% and 98.6%. The HI test and commercial ELISA kit (IDEXX) separately agreed 97.83% and 98.1% with cELISA when testing clinical chicken sera and both agreed 100% when testing egg yolks. However, for detecting anti-NDV antibodies in the sequential sera from the challenged chickens, cELISA demonstrated to be more sensitive than the HI test and commercial ELISA kit. Moreover, a close correlation (R2 = 0.914) was found between the percent competitive inhibition values of cELISA and HI titers. CONCLUSIONS: A platform was successfully designed to easily and rapidly produce the nanobody-HRP fusion protein, which was the first time to be used as reagents for establishing cELISA. Results suggest that the platform supports the development of a cELISA with high sensitivity, simplicity, and rapid detection of anti-NDV antibodies. Overall, we believe that the platform based on nanobody-HRP fusions can be widely used for future investigations and treatment other diseases and viruses.

Dietary curcumin supplementation attenuates inflammation, hepatic injury and oxidative damage in a rat model of intra-uterine growth retardation.

Rats with a normal birth weight (NBW) or intra-uterine growth retardation (IUGR) were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NC and IC groups) from 6 to 12 weeks. The body weight of IUGR rats was lower (P<0·05) than that of the controls. Rats with IUGR showed higher (P<0·05) concentrations of TNF-α, IL-1ß and IL-6; higher (P<0·05) activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in their serum; and increased (P<0·05) concentrations of malondialdehyde (MDA), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHDG) in the liver compared with the NBW rats. The livers of IUGR rats exhibited a lower (P<0·05) superoxide dismutase activity and decreased (P<0·05) metabolic efficiency of the hepatic glutathione redox cycle compared with those of the NBW rats. In response to dietary curcumin supplementation, concentrations of inflammatory cytokines and activities of AST and ALT in the serum and MDA, PC and 8-OHDG in the liver were lower (P<0·05), and the hepatic glutathione redox cycle in the liver was improved (P<0·05) in the IC group than in the IUGR group. These results were associated with lower (P<0·05) phosphorylated levels of the NF-κB pathway and Janus kinase 2 (JAK2) and higher (P<0·05) mRNA expression of genes involved in the nuclear factor, erythroid 2-like 2 (Nfe2l2)/antioxidant response element (ARE) pathway in the liver of the IC rats than that of the IUGR rats. Maternal undernutrition decreased birth weight and led to inflammation, oxidative damage and injury in rats. Curcumin appeared to be beneficial in preventing IUGR-induced inflammation, oxidative damage and injury by activating the expression of the NF-κB, JAK/STAT and Nfe2l2/ARE pathways in the liver.

N-acetylcysteine attenuates intrauterine growth retardation-induced hepatic damage in suckling piglets by improving glutathione synthesis and cellular homeostasis.

PURPOSE: The objective of the present study was to test the hypothesis that N-acetylcysteine (NAC) may play beneficial roles against intrauterine growth retardation (IUGR)-induced hepatic damage in suckling piglets. METHODS: Fourteen IUGR and seven normal birth weight (NBW) neonatal male piglets were selected. Piglets were weaned at 7 days of postnatal age and fed the control formula milk (NBW-CON and IUGR-CON groups) or the control formula milk supplemented with 1.2 g/kg NAC (IUGR-NAC group) for 14 days (n = 7). The plasma and liver samples were analyzed for the parameters related to hepatic damage, redox status, apoptosis, and autophagy. RESULTS: Compared with the NBW-CON group, IUGR-CON group exhibited increased activities of plasma aminotransferases, increased numbers of apoptotic hepatocytes, as well as higher concentrations of protein carbonyl, malondialdehyde (MDA), microtubule-associated protein 1 light chain 3 beta, and phospholipid-conjugated form (MAP1LC3B-II), along with a decrease in the content of reduced glutathione (GSH). NAC treatment increased GSH content and GSH-to-oxidized GSH ratio in the liver of IUGR-NAC group, most likely owing to the improved activities of γ-glutamine-cysteine ligase, γ-glutamine-cysteine synthetase, and glutathione reductase. The hepatic protein carbonyl and MDA contents were decreased in the IUGR-NAC group compared with the IUGR-CON group. In addition, NAC-treated piglets had an increased content of B cell lymphoma/leukemia 2 protein, whereas a decreased expression level of MAP1LC3B-II in the liver. CONCLUSIONS: NAC may have beneficial effects in improving GSH synthesis and cellular homeostasis in the liver of IUGR suckling piglets.

Second-order quasi-likelihood for spatial point processes.

Applications of spatial point processes for large and complex data sets with inhomogeneities as encountered, example, in tropical rain forest ecology call for estimation methods that are both statistically and computationally efficient. We propose a novel second-order quasi-likelihood procedure to estimate the parameters for a second-order intensity reweighted stationary spatial point process. Our approach is to derive first- and second-order estimating functions and then combine them linearly using appropriate weight functions. In the stationary case, we argue that the asymptotically optimal weight functions are respectively a constant and a function of lags between distinct locations in the observation window. This leads to a considerable gain in computational efficiency. We further exploit this simplification in the nonstationary case. Simulations show that, when compared with several existing approaches, our method can achieve significant gains in statistical efficiency. An application to a tropical rain forest data set further illustrates the advantages of our procedure.

Dietary enzymatically treated Artemisia annua L. supplementation alleviates liver oxidative injury of broilers reared under high ambient temperature.

Heat stress induced by high ambient temperature is a major concern in commercial broiler production. To evaluate the effects of dietary enzymatically treated Artemisia annua L. (EA) supplementation on growth performance and liver oxidative injury of broilers reared under heat stress, a total of 320 22-day-old male broilers were randomly allotted into five groups with eight replicates of eight birds each. Broilers in the control group were housed at 22 ± 1 °C and fed the basal diet. Broilers in the HS, HS-EA1, HS-EA2, and HS-EA3 groups were fed basal diet supplemented with 0, 0.75, 1.00, and 1.25 g/kg EA, respectively, and reared under cyclic high temperature (34 ± 1 °C for 8 h/day and 22 ± 1 °C for 16 h/day). Broilers fed EA diets had higher final body weight, average daily body weight gain, and average daily feed intake, as well as liver concentration of reduced glutathione, activities of antioxidant enzymes, abilities to inhibit hydroxyl radical and superoxide radical (HS-EA2 and HS-EA3), and lower liver concentrations of reactive oxygen metabolites, malondialdehyde, and protein carbonyl (HS-EA1, HS-EA2, and HS-EA3) than HS group (P < 0.05). EA treatment downregulated the mRNA levels of heat shock proteins 70 and 90, upregulated the mRNA levels of nuclear factor erythroid 2-related factor 2 (HS-EA1, HS-EA2, and HS-EA3) and heme oxygenase 1 (HS-EA2 and HS-EA3) in liver of heat-treated broilers (P < 0.05). In conclusion, EA alleviated heat stress-induced growth depression and liver oxidative injury in broilers, possibly through improving the antioxidant capacity and regulating the pertinent mRNA expression. The appropriate inclusion level of EA in broiler diet is 1.00-1.25 g/kg.

Hermetically Coated and Well-Separated Co3 O4 Nanophase within Porous Graphitic Carbon Nanosheets: Synthesis, Confinement Effect, and Improved Lithium-Storage Capacity and Durability.

Considerable lithium-driven volume changes and loss of crystallinity on cycling have impeded the sustainable use of transition metal oxides (MOs) as attractive anode materials for advanced lithium-ion batteries that have almost six times the capacity of carbon per unit volume. Herein, Co3 O4 was used as a model MO in a facile process involving two pyrolysis steps for in situ encapsulation of nanosized MO in porous two-dimensional graphitic carbon nanosheets (2D-GCNs) with high surface areas and abundant active sites to overcome the above-mentioned problems. The proposed method is inexpensive, industrially scalable, and easy to operate with a high yield. TEM revealed that the encaged Co3 O4 is well separated and uniformly dispersed with surrounding onionlike graphitic layers. By taking advantage of the high electronic conductivity and confinement effect of the surrounding 2D-GCNs, a hierarchical GCNs-coated Co3 O4 (Co3 O4 @GCNs) anode with 43.5 wt % entrapped active nanoparticles delivered a remarkable initial specific capacity of 1816 mAh g(-1) at a current density of 100 mA g(-1) . After 50 cycles, the retained capacity is as high as 987 mAh g(-1) . When the current density was increased to 1000 mA g(-1) , the anode showed a capacity retention of 416 mAh g(-1) . Enhanced reversible rate capability and prolonged cycling stability were found for Co3 O4 @GCN compared to pure GCNs and Co3 O4 . The Co3 O4 @GCNs hybrid holds promise as an efficient candidate material for anodes due to its low cost, environmentally friendly nature, high capacity, and stability.

Efficient fabrication of high-capacity immobilized metal ion affinity chromatographic media: The role of the dextran-grafting process and its manipulation.

Novel high-capacity Ni(2+) immobilized metal ion affinity chromatographic media were prepared through the dextran-grafting process. Dextran was grafted to an allyl-activated agarose-based matrix followed by functionalization for the immobilized metal ion affinity chromatographic media. With elaborate regulation of the allylation degree, dextran was completely or partly grafted to agarose microspheres, namely, completely dextran-grafted agarose microspheres and partly dextran-grafted ones, respectively. Confocal laser scanning microscope results demonstrated that a good adjustment of dextran-grafting degree was achieved, and dextran was distributed uniformly in whole completely dextran-grafted microspheres, while just distributed around the outside of the partly dextran-grafted ones. Flow hydrodynamic properties were improved greatly after the dextran-grafting process, and the flow velocity increased by about 30% compared with that of a commercial chromatographic medium (Ni Sepharose FF). A significant improvement of protein binding performance was also achieved by the dextran-grafting process, and partly dextran-grafted Ni(2+) chelating medium had a maximum binding capacity for His-tagged lactate dehydrogenase about 2.5 times higher than that of Ni Sepharose FF. The results indicated that this novel chromatographic medium is promising for applications in high-efficiency and large-scale protein purification.

Curcumin attenuates D-galactosamine/lipopolysaccharide-induced liver injury and mitochondrial dysfunction in mice.

Curcumin, a naturally occurring antioxidant, has various beneficial effects in the treatment of human diseases. However, little information regarding the protection it provides against acute liver injury is available. The present study investigated the protective effects of curcumin against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in mice. A total of 40 male Kunming mice were randomly assigned to 5 groups: 1) mice administered saline vehicle injection (control), 2) mice administered 200 mg/kg body weight (BW) curcumin by i.p. injection (CUR), 3) mice administered D-GalN/LPS (700 mg and 5 µg/kg BW) via i.p. injection (GL), 4) mice administered 200 mg/kg BW curcumin i.p. 1 h before D-GalN/LPS injection (CUR-GL), and 5) mice administered 200 mg/kg BW curcumin i.p. 1 h after D-GalN/LPS injection (GL-CUR). Twenty h after D-GalN/LPS injection, serum alanine aminotransferase activities were 18.5% and 13.5% lower (P < 0.05) and aspartate aminotransferase (AST) activities were 26.6% and 9.6% lower (P < 0.05) in the CUR-GL and GL-CUR groups, respectively, than in the GL group. The CUR-GL and GL-CUR groups had 64.4% and 15.0% higher (P < 0.05) mitochondrial membrane potentials, respectively, and the CUR-GL group had a 44.7% lower reactive oxygen species concentration than the GL group (P < 0.05). Mitochondrial manganese superoxide dismutase activities were 111% and 77.9% higher (P < 0.05) and the percentages of necrotic cells were 47.0% and 32.4% lower (P < 0.05) in the CUR-GL and GL-CUR groups, respectively, than in the GL group. Liver mRNA levels of sirtuin 1 (Sirt1) were 56.4% lower (P < 0.05) in the CUR-GL group than in the GL group. Moreover, compared with the GL-CUR group, the CUR-GL group had an 18.7% lower serum AST activity, a 31.7% lower mitochondrial malondialdehyde concentration, a 36.0% lower hepatic reactive oxygen species concentration, and a 43.0% higher mitochondrial membrane potential. These results suggested that curcumin protects against D-GalN/LPS-induced liver damage by the enhancing antioxidant defense system, attenuating mitochondrial dysfunction and inhibiting apoptosis. This was especially true for curcumin pretreatment, which highlighted its promise as a preventive treatment for acute liver injury in clinical settings.

Estimating cell-type-specific gene co-expression networks from bulk gene expression data with an application to Alzheimer's disease.

Inferring and characterizing gene co-expression networks has led to important insights on the molecular mechanisms of complex diseases. Most co-expression analyses to date have been performed on gene expression data collected from bulk tissues with different cell type compositions across samples. As a result, the co-expression estimates only offer an aggregated view of the underlying gene regulations and can be confounded by heterogeneity in cell type compositions, failing to reveal gene coordination that may be distinct across different cell types. In this paper, we introduce a flexible framework for estimating cell-type-specific gene co-expression networks from bulk sample data, without making specific assumptions on the distributions of gene expression profiles in different cell types. We develop a novel sparse least squares estimator, referred to as CSNet, that is efficient to implement and has good theoretical properties. Using CSNet, we analyzed the bulk gene expression data from a cohort study on Alzheimer's disease and identified previously unknown cell-type-specific co-expressions among Alzheimer's disease risk genes, suggesting cell-type-specific disease mechanisms.

Effects of different seat inclination angles on lumbar dynamic response and injury during lunar-earth reentry.

The inclination angle of the spacecraft seat is related to the astronaut's reentry angle, which in turn affects the safety of the astronauts. This study quantitatively analyzed the effects of different seat inclination angles on astronauts' lumbar spine injuries using the finite element method during the Lunar-Earth reentry. Firstly, a finite element model of the astronaut's lumbar spine was constructed based on reverse engineering technology, and the effectiveness of the model was verified through mesh sensitivity, vertebral range of motion, and spinal impact experiments. Then, simulation calculations were carried out for different seat inclination angles (0°, 10°, 20°, and 30°) under the typical reentry return loads of Chang'e 5T1 (CE-5T1) and Apollo 10, and the prediction and evaluation of lumbar spine injuries were conducted in conjunction with the biological tissue injury criteria. The results indicated that the stress on the vertebrae and annulus fibrosus increased under both reentry loads with the rise of the seat inclination angle, but the increasing rates decreased. When the acceleration peak of CE-5T1 approached 9G, the risk of tissue injury was higher under the seat angle exceeded 20°. According to the Multi-Axis Dynamic Response Criteria for spinal injury, neither of the two load conditions would directly cause injury to the astronauts' lumbar spine when the seat inclination angle was below 30°. The study findings provide a numerical basis for designing and improving the spacecraft's inclination angle in crewed lunar missions, ensuring the safety of astronauts.