Surviving winter on the Qinghai-Xizang Plateau:Extensive reversible protein phosphorylation plays a dominant role in regulating hypometabolism in hibernating Nanorana parkeri

Changes in protein abundance and reversible protein phosphorylation(RPP)play important roles in regulating hypometabolism but have never been documented in overwintering frogs at high altitudes.To test the hypothesis that protein abundance and phosphorylation change in response to winter hibernation,we conducted a comprehensive and quantitative proteomic and phosphoproteomic analysis of the liver of the Xizang plateau frog,Nanorana parkeri,living on the Qinghai-Xizang Plateau.In total,5170 proteins and 5695 phosphorylation sites in 1938 proteins were quantified.Based on proteomic analysis,674 differentially expressed proteins(438 up-regulated,236 down-regulated)were screened in hibernating N.parkeri versus summer individuals.Functional enrichment analysis revealed that higher expressed proteins in winter were significantly enriched in immune-related signaling pathways,whereas lower expressed proteins were mainly involved in metabolic processes.A total of 4251 modified sites(4147 up-regulated,104 down-regulated)belonging to 1638 phosphoproteins(1555 up-regulated,83 down-regulated)were significantly changed in the liver.During hibernation,RPP regulated a diverse array of proteins involved in multiple functions,including metabolic enzymatic activity,ion transport,protein turnover,signal transduction,and alternative splicing.These changes contribute to enhancing protection,suppressing energy-consuming processes,and inducing metabolic depression.Moreover,the activities of phosphofructokinase,glutamate dehydrogenase,and ATPase were all significantly lower in winter compared to summer.In conclusion,our results support the hypothesis and demonstrate the importance of RPP as a regulatory mechanism when animals transition into a hypometabolic state.

Secreted Frizzled-Related Protein 5 Mediates Wnt5a Expression in Microcystin-Leucine-Arginine-Induced Liver Lipid Metabolism Disorder in Mice

Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway.Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

Effects of different energy levels in low-protein diet on liver lipid metabolism in the late-phase laying hens through the gut-liver axis

Background The energy/protein imbalance in a low-protein diet induces lipid metabolism disorders in late-phase laying hens.Reducing energy levels in the low-protein diet to adjust the energy-to-protein ratio may improve fat deposition,but this also decreases the laying performance of hens.This study investigated the mechanism by which different energy levels in the low-protein diet influences liver lipid metabolism in late-phase laying hens through the enterohepatic axis to guide feed optimization and nutrition strategies.A total of 288 laying hens were randomly allocated to the normal-energy and normal-protein diet group(positive control:CK)or 1 of 3 groups:lowenergy and low-protein diet(LL),normal-energy and low-protein diet(NL),and high-energy and low-protein diet(HL)groups.The energy-to-protein ratios of the CK,LL,NL,and HL diets were 0.67,0.74,0.77,and 0.80,respectively.Results Compared with the CK group,egg quality deteriorated with increasing energy intake in late-phase laying hens fed low-protein diet.Hens fed LL,NL,and HL diets had significantly higher triglyceride,total cholesterol,acetylCo A carboxylase,and fatty acid synthase levels,but significantly lower hepatic lipase levels compared with the CK group.Liver transcriptome sequencing revealed that genes involved in fatty acid beta-oxidation(ACOX1,HADHA,EHHADH,and ACAA1)were downregulated,whereas genes related to fatty acid synthesis(SCD,FASN,and ACACA)were upregulated in LL group compared with the CK group.Comparison of the cecal microbiome showed that in hens fed an LL diet,Lactobacillus and Desulfovibrio were enriched,whereas riboflavin metabolism was suppressed.Cecal metabolites that were most significantly affected by the LL diet included several vitamins,such as riboflavin(vitamin B2),pantethine(vitamin B5 derivative),pyridoxine(vitamin B6),and 4-pyridoxic acid.Conclusion A lipid metabolism disorder due to deficiencies of vitamin B2 and pantethine originating from the metabolism of the cecal microbiome may be the underlying reason for fat accumulation in the liver of late-phase laying hens fed an LL diet.Based on the present study,we propose that targeting vitamin B2 and pantethine(vitamin B5 derivative)might be an effective strategy for improving lipid metabolism in late-phase laying hens fed a low-protein diet.

Protein succinylation,hepatic metabolism,and liver diseases

Succinylation is a highly conserved post-translational modication that is processed via enzymatic and non-enzymatic mechanisms.Succinylation exhibits strong effects on protein stability,enzyme activity,and transcriptional regulation.Protein succinylation is extensively present in the liver,and increasing evidence has demonstrated that succinylation is closely related to hepatic metabolism.For instance,histone acetyltransferase 1 promotes liver glycolysis,and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid metabolism.Therefore,the effects of succinylation on hepatic glucose,amino acid,and lipid metabolism under the action of various enzymes will be discussed in this work.In addition,how succinylases regulate the progression of different liver diseases will be reviewed,including the desuccinylation activity of sirtuin 7,which is closely associated with fatty liver disease and hepatitis,and the actions of lysine acetyltransferase 2A and histone acetyltransferase 1 that act as succinyltransferases to regulate the succinylation of target genes that influence the development of hepatocellular carcinoma.In view of the diversity and significance of protein succinylation,targeting the succinylation pathway may serve as an attractive direction for the treatment of liver diseases.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

Lactate metabolism in neurodegenerative diseases

Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Gut microbiota remodeling drived by dietary millet protein prevents the metabolic syndrome

Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota homeostasis.Metabolites derived from gut microbes play essential roles in Met S prevention and therapy.Here,we focused on the inhibitory effect of the extract of millet bran protein(EMBP)on a high-fat diet(HFD)-induced Met S,aiming to identify gut microbiota and their metabolites that involve in the anti-Met S activity of EMBP.The obesity,chronic inflammation,insulin resistance in Met S mouse models were abolished after EMBP treatment.The protective mechanism of EMBP against HFD-induced Met S may depend on improved gut barrier function.Using microbiome analysis,we found that EMBP supplementation improved gut microbiome dysbiosis in Met S mice,specifically upregulating Bacteroides acidifaciens.The fecal microbiota transplantation(FMT)also demonstrated this phenomenon.In addition,metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in Met S mice.Notably,a microbiota-derived metabolite,gamma-aminobutyric acid(GABA),is enriched by EMBP.In addition,exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFDinduced Met S.The results suggest that EMBP suppress host Met S by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Predictive value of angiopoietin-like protein 8 in metabolic dysfunction-associated fatty liver disease and its progression:A case-control study

BACKGROUND The prevalence of metabolic dysfunction-associated fatty liver disease(MAFLD)is rapidly increasing,currently affecting approximately 25%of the global population.Liver fibrosis represents a crucial stage in the development of MAFLD,with advanced liver fibrosis elevating the risks of cirrhosis and hepatocellular carcinoma.Simple serum markers are less effective in diagnosing liver fibrosis compared to more complex markers.However,imaging techniques like transient elastography face limitations in clinical application due to equipment and technical constraints.Consequently,it is imperative to identify a straightforward yet effective method for assessing MAFLD-associated liver fibrosis.AIM To investigate the predictive value of angiopoietin-like protein 8(ANGPTL8)in MAFLD and its progression.METHODS We analyzed 160 patients who underwent abdominal ultrasonography in the Endocrinology Department,Xiaogan Central Hospital affiliated to Wuhan University of Science and Technology,during September 2021-July 2022.Using abdominal ultrasonography and MAFLD diagnostic criteria,among the 160 patients,80 patients(50%)were diagnosed with MAFLD.The MAFLD group was divided into the liver fibrosis group(n=23)and non-liver fibrosis group(n=57)by using a cut-off fibrosis-4 index≥1.45.Logistical regression was used to analyze the risk of MAFLD and the risk factors for its progression.Receiver operating characteristic curves were used to evaluate the predictive value of serum ANGPTL8 in MAFLD and its progression.RESULTS Compared with non-MAFLD patients,MAFLD patients had higher serum ANGPTL8 and triglyceride-glucose(TyG)index(both P<0.05).Serum ANGPTL8(r=0.576,P<0.001)and TyG index(r=0.473,P<0.001)were positively correlated with MAFLD.Serum ANGPTL8 was a risk factor for MAFLD[odds ratio(OR):1.123,95%confidence interval(CI):1.066-1.184,P<0.001).Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD[area under the curve(AUC):0.832 and 0.886,respectively;both P<0.05].Compared with MAFLD patients without fibrosis,those with fibrosis had higher serum ANGPTL8 and TyG index(both P<0.05),and both parameters were positively correlated with MAFLD-associated fibrosis.Elevated serum ANGPTL8(OR:1.093,95%CI:1.044-1.144,P<0.001)and TyG index(OR:2.383,95%CI:1.199-4.736,P<0.013)were risk factors for MAFLD-associated fibrosis.Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD-associated fibrosis(AUC:0.812 and 0.835,respectively;both P<0.05).CONCLUSION The serum levels of ANGPTL8 are elevated and positively correlated with MAFLD.They can serve as predictors for the risk of MAFLD and liver fibrosis,with the ANGPTL8+TyG index potentially exhibiting even higher predictive value.

Nutritional Metabolism of Antarctic Krill Product Protein in Rats

This work conducted a four-week metabolism test on rats to study the digestion and absorption characteristics of five protein-based krill products prepared from Antarctic krill as raw material.It aimed to provide theoretical support for the effective use of Antarctic krill protein and the development of novel protein resources.The results showed that the weight gain and true digestibility of the rats fed with krill meat,surimi and ordinary krill powder were significantly higher(P<0.05)than those of the rats fed with traditional casein.Compared to casein,proteins from the five Antarctic krill products were found to significantly improve the net protein utilization(P<0.05),and reduce the total cholesterol and triglycerides in the serum of rats(P<0.05).In summary,the Antarctic krill protein-based products with high nutritional values can be used as a potential novel protein resource in the food industry.

Effects of Astragalus membranaceus on Energy Metabolism and Expression of CNTF Protein in Skeletal Muscle of Exercise-induced Fatigue Rats

[Objectives]This study was conducted to investigate the effects of Astragalus membranaceus in different groups on energy metabolism and CNTF protein expression in skeletal muscle of exercise-induced fatigue rats.[Methods]Thirty-five clean male SD rats were randomly divided into a normal group,and low-,meddle-and high-dose groups of A.membranaceus aqueous solution,with 7 rats in each group.The low-dose,medium-dose and high-dose groups were given by gavage at 0.65,1.3 and 2.6 g/kg,respectively,while the normal group and the model group were given normal food and water.The weight of rats was observed.The contents of serum urea,lactate,muscle glycogen,liver glycogen and CNTF expression were detected.[Results]After modeling,compared with the normal group,the serum lactate and urea contents of rats in the model group significantly increased(P<0.01),while the muscle glycogen content(P<0.01)and liver glycogen content(P<0.05)of the skeletal muscle significantly decreased.Compared with the model group,the low-,meddle-and high-dose groups of A.membranaceus significantly reduced the levels of lactate and urea in serum(P<0.01),while the levels of muscle glycogen and liver glycogen in the skeletal muscle significantly increased(P<0.01,P<0.05).[Conclusions]This study provides a good research foundation for the treatment of exercise-induced fatigue using traditional Chinese herb A.membranaceus in modern clinical practice.

Effects of Chinese herbal medicine on plasma glucose,protein and energy metabolism in sheep

Background： The use of antibiotics in animal diets is facing negative feedback due to the hidden danger of drug residues to human health. Traditional Chinese herbal medicine has been used to replace antibiotics in the past two decades and played an increasingly important role in livestock production. The present study was carried out to assess the feeding effects of a traditional nourishing Chinese herbal medicine mixture on kinetics of plasma glucose, protein and energy metabolism in sheep. Ruminal fermentation characteristics were also determined. Methods： Four sheep were fed on either mixed hay （MH-diet） or MH-diet supplemented with 2% of Chinese herbal medicine （mixture of Astragalus root, Angelica root and Atractylodes rhizome; CHM-diet） over two 3S-day periods using a crossover design. The turnover rate of plasma glucose was measured with an isotope dilution method using [U-^13C]glucose. The rates of plasma leucine turnover and leucine oxidation, whole body protein synthesis （WBPS） and metabolic heat production were measured using the [1-^13C]leucine dilution and open circuit calorimetry. Results： Body weight gain of sheep was higher （P = 0.03） for CHM-diet than for MH-diet. Rumen pH was lower （P = 0.02）, concentration of rumen total volatile fatty acid tended to be higher （P = 0.05） and acetate was higher （P = 0.04） for CHM-diet than for MH-diet. Turnover rates of plasma glucose and leucine did not differ between diets. Oxidation rate of leucine tended to be higher （P = 0.06） for CHM-diet than for MH-diet, but the WBPS did not differ between diets. Metabolic heat production tended to be greater （P = 0.05） for CHM-diet than for MH-diet. Conclusions： The sheep fed on CHM-diet had a higher body weight gain and showed positive impacts on rumen fermentation and energy metabolism without resulting in any adverse response. Therefore, these results suggested that the Chinese herbal medicine mixture should be considered as a potential feed additive for sheep.

Effects of Uniconazole on Nitrogen Metabolism and Grain Protein Content of Rice

The effects of uniconazole by soaking seeds and spraying leaves at booting stage with different concentrations （0, 20 and 40 mg/kg） on the nitrogen metabolism of flag leaf and grains after flowering, and rice grain protein content and yield were studied with hybrid rice combination Shanyou 63. Under uniconazole treatment, the soluble protein content in flag leaf was increased in early and middle period of grain filling, but this content was nearly the same as or even lower than that of control at maturity; Glutamine synthetase activity in superior and inferior grains and non-protein nitrogen content in superior grains at early stage of grain development were promoted, and moreover, the transforming speed from non-protein nitrogen to protein nitrogen was accelerated; Non-protein nitrogen content was lower than that of control at maturity, but protein nitrogen content at each stage was higher than those of control; Protein nitrogen content in superior and inferior grains and protein nitrogen absolutely accumulative content in a grain both were enhanced and protein content and yield in rice grain were raised. The application of uniconazole by soaking seeds and spraying leaves raised crude protein content by an average of 7.2% and 8.3%, and protein yield by an average of 13.1% and 13.4%, respectively.

Effects of Dietary Corn Gluten Meal on Growth Performance and Protein Metabolism in Relation to IGF-I and TOR Gene Expression of Juvenile Cobia (Rachycentron canadum)

A growth experiment was conducted on cobia(Rachycentron canadum,initial weight 108.2 g ± 3.0 g) to investigate the effects of dietary corn gluten meal(CGM) levels on the fish growth,whole body composition and protein metabolism in relation to specific gene expression.Five isonitrogenous(crude protein 45%) and isoenergetic(gross energy 20 kJ g 1) practical diets were formulated by replacing 0%(the control),17.5%,35.0%,52.5%,and 70.0% of fish meal(FM) protein with CGM protein.No significant differences were observed in the survival,feed intake(FI),specific growth rate(SGR),feed efficiency(FE) and protein productive value(PPV) among fish fed diets with 0%,17.5%,35.0%,and 52.5% of CGM protein.However,these indices were significantly lower in fish fed the diet with 70.0% of CGM protein than those in fish fed the control diet(P < 0.05).The whole-body crude protein and lipid contents were significantly lower while the whole-body moisture content was significantly higher in fish fed the diet with 70.0% of CGM protein compared with the control group(P < 0.05).When 70.0% of FM protein was replaced by CGM,plasma total protein and cholesterol contents were significantly lower than those in the control group(P < 0.05).Fish fed the diet with 70.0% of CGM protein had significantly lower hepatic insulin-like growth factor I(IGF-I) expression levels than those in the control group(P < 0.05).However,no significant differences were observed in hepatic target of rapamycin(TOR),dorsal muscle IGF-I and TOR expression levels among dietary treatments.Results of the present study indicated that 52.5% of FM protein could be replaced by CGM in the diets without significant influences on the growth,feed utilization and protein metabolism of juvenile cobia.The present results might be useful for developing cost effective and sustainable cobia dietary formulations.

Inhibition of protein degradation increases the Bt protein concentration in Bt cotton

Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s organs.Therefore,increasing the Bt protein concentration at the boll stage,especially in bolls,has become the main goal for increasing insect resistance in cotton.In this study,two protein degradation inhibitors(ethylene diamine tetra acetic acid(EDTA)and leupeptin)were sprayed on the bolls,subtending leaves,and whole cotton plants at the peak flowering stage of two Bt cultivars(medium maturation Sikang 1(SK1))and early maturation Zhongmian 425(ZM425)in 2019 and 2020.The Bt protein content and protein degradation metabolism were assessed.The results showed that the Bt protein concentrations were enhanced by 21.3 to 38.8%and 25.0 to 38.6%in the treated bolls of SK1 and ZM425 respectively,while they were decreased in the subtending leaves of these treated bolls.In the treated leaves,the Bt protein concentrations increased by 7.6 to 23.5%and 11.2 to 14.9%in SK1 and ZM425,respectively.The combined application of EDTA and leupeptin to the whole cotton plant increased the Bt protein concentrations in both bolls and subtending leaves.The Bt protein concentrations in bolls were higher,increasing by 22.5 to 31.0%and 19.6 to 32.5%for SK1 and ZM425,respectively.The organs treated with EDTA or/and leupeptin showed reduced free amino acid contents,protease and peptidase activities and significant enhancements in soluble protein contents.These results indicated that inhibiting protein degradation could improve the protein content,thus increasing the Bt protein concentrations in the bolls or/and leaves of cotton plants.Therefore,the increase in the Bt protein concentration without yield reduction suggested that these two protein degradation inhibitors may be applicable for improving insect resistance in cotton production.

The unfolded protein response signaling and retinal Müller cell metabolism

The retina is one of the most energy demanding tissues in the body. Like most neurons in the central nervous system, retinal neurons consume high amounts of adenosine-5′-triphosphate（ATP） to generate visual signal and transmit the information to the brain. Disruptions in retinal metabolism can cause neuronal dysfunction and degeneration resulting in severe visual impairment and even blindness. The homeostasis of retinal metabolism is tightly controlled by multiple signaling pathways, such as the unfolded protein response（UPR）, and the close interactions between retinal neurons and other retinal cell types including vascular cells and Müller glia. The UPR is a highly conserved adaptive cellular response and can be triggered by many physiological stressors and pathophysiological conditions. Activation of the UPR leads to changes in glycolytic rate, ATP production, de novo serine synthesis, and the hexosamine biosynthetic pathway, which are considered critical components of Müller glia metabolism and provide metabolic support to surrounding neurons. When these pathways are disrupted, neurodegeneration occurs rapidly. In this review, we summarize recent advance in studies of the UPR in Müller glia and highlight the potential role of the UPR in retinal degeneration through regulation of Müller glia metabolism.

Dynamics of Bt cotton Cry1Ac protein content under an alternating high temperature regime and effects on nitrogen metabolism

This study was conducted to investigate the effects of alternating high temperature on CrylAc protein content on Bt cotton cultivars Sikang 1 （SK-1, a conventional cultivar） and Sikang 3 （SK-3, a hybrid cultivar）. In 2011 and 2012, cotton plants were subjected to high temperature treatments ranging from 32 to 40℃ in climate chambers to investigate the effects of high temperature on boll shell insecticidal protein expression. The experiments showed that significant decline of the boll shell insecticidal protein was detected at temperatures higher than 38℃ after 24 h. Based on the results, the cotton plants were treated with the threshold temperature of 38℃ from 6：00 a.m. to 6：00 p.m. followed by a normal temperature of 27℃ during the remaining night hours （DH/NN） in 2012 and 2013. These treatments were conducted at peak boll growth stage for both cultivars in study periods of 0, 4, 7, and 10 d. Temperature treatment of 32℃ from 6：00 a.m. to 6：00 p.m. and 27℃ in the remaining hours was set as control. The results showed that, compared with the control, after the DH/NN stress treatment applied for 7 d, the boll shell CrylAc protein content level was significantly decreased by 19.1 and 17.5% for SK-1 and by 15.3 and 13.7% for SK-3 in 2012 and 2013, respectively. Further analysis of nitrogen metabolic physiology under DH/NN showed that the soluble protein content and the glutamic pyruvic transaminase （GPT） activities decreased slightly after 4 d, and then decreased sharply after 7 d. The free amino acid content and the protease content increased sharply after 7 d. The changes in SK-1 were greater than those in SK-3. These results suggest that under DH/NN stress, boll shell CrylAc protein content decline was delayed. Reduced protein synthesis and increased protein degradation in the boll shell decreased protein content, including Bt protein, which may reduce resistance to the cotton bollworm.

Optimizing the Bacillus thuringiensis(Bt)protein concentration in cotton:Coordinated application of exogenous amino acids and EDTA to reduce spatiotemporal variability in boll and leaf toxins

During the boll formation stage,cotton bolls exhibit the lowest expression of Bacillus thuringiensis(Bt)insecticidal proteins.Resistance to insects varies notably among different organs,which poses challenges for controlling cotton bollworms.Consequently,an experimental strategy was designed in the 2020-2021 cotton growing season to coordinate the enhancement of protein synthesis and the attenuation of degradation.Two Bt cultivars of Gossypium hirsutum,namely the hybrid Sikang 3 and the conventional Sikang 1,were used as test materials.Three treatments were applied at the peak flowering period:CK(the control),T1(amino acids),and T2(amino acids and EDTA).The results show that,in comparison to the CK group,the Bt protein contents were significantly increased in both cotton bolls and their subtending leaves under the T1 and T2 treatments.The maximum levels of increase observed were 67.5%in cotton bolls and 21.7%in leaves.Moreover,the disparity in Bt protein content between cotton bolls and their subtending leaves notably decreased by 31.2%.Correlation analysis suggested that the primary physiological mechanisms for augmenting Bt protein content involve increased protein synthesis and reduced protein catabolism,which are independent of Bt gene expression levels.Stepwise regression and path analysis revealed that elevating the soluble protein content and transaminase activity,while reducing the catabolic enzyme activities,are instrumental in enhancing the Bt protein content.Consequently,the coordinated application of amino acids and EDTA emerges as a strategy that can improve the overall resistance of Bt cotton and mitigate the spatiotemporal variations in Bt toxin concentrations in both cotton bolls and leaves.

Effect of Dietary Folic Acid Supplementation on Growth Performance and Hepatic Protein Metabolism in Early-Weaned Intrauterine Growth Retardation Piglets

To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation （IUGR） piglets, 24 male （Durocx （LandracexYorkshire）） weaned （14-d-old） IUGR piglets were randomly divided into 3 treatments with 8 replicates of 1 piglet per replicate. The piglets in each treatment were fed basal diet supplementation with either 0 （control）, 5 and 10 mg kg^-1 folic acid. The trial lasted for 21 d. Dietary folic acid supplementation reduced average daily feed intake （ADFI） （P〈0.05）. In addition, the average daily gain （ADG） in 10 mg kg^-1 folic acid group was significantly decreased （P〈0.01） and the ratio of feed：gain （F/G） increased slightly （P〉0.05）. Serum folic acid concentration increased （P〈0.01） with increasing folic acid inclusion, however, serum homocysteine concentration decreased significantly （P〈0.01）. Enhanced serum urine nitrogen （SUN） and diminished serum total protein （TP） as well as liver TP content were observed in 10 mg kg^-1 folic acid group （/＇〈0.05）. Furthermore, the relative mRNA expressions of insulin-like growth factor 1 （IGF-1） and mammalian target of rapamycin （m-TOR） in liver were respectively tended to reduce （P=0.06） and significantly downregulated （P〈0.05） in 10 mg kg1 group, in compared with 5 mg kg1 group. However, when compared with control group, folic acid supplementation had no significant effect on the mRNA abundance of IGF- 1 and m-TOR. The results indicated that supplementation with 10 mg kg-I folic acid impaired growth performance and hepatic protein metabolism of early-weaned IUGR piglets while 5 mg kg-~ folic acid enriched diet exerted limited positive effects.