Deficit of PKHD1L1 in the dentate gyrus increases seizure susceptibility in mice.

Epilepsy is a chronic neurological disorder featuring recurrent, unprovoked seizures, which affect more than 65 million people worldwide. Here, we discover that the PKHD1L1, which is encoded by polycystic kidney and hepatic disease1-like 1 (Pkhd1l1), wildly distributes in neurons in the central nervous system (CNS) of mice. Disruption of PKHD1L1 in the dentate gyrus region of the hippocampus leads to increased susceptibility to pentylenetetrazol-induced seizures in mice. The disturbance of PKHD1L1 leads to the overactivation of the mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK)-Calpain pathway, which is accompanied by remarkable degradation of cytoplasmic potassium chloride co-transporter 2 (KCC2) level together with the impaired expression and function of membrane KCC2. However, the reduction of membrane KCC2 is associated with the damaged inhibitory ability of the vital GABA receptors, which ultimately leads to the significantly increased susceptibility to epileptic seizures. Our data, thus, indicate for the first time that Pkhd1l1, a newly discovered polycystic kidney disease (PKD) association gene, is required in neurons to maintain neuronal excitability by regulation of KCC2 expression in CNS. A new mechanism of the clinical association between genetic PKD and seizures has been built, which could be a potential therapeutic target for treating PKD-related seizures.

Extrusion puffing as a pretreatment method to change the surface structure, physicochemical properties and in vitro protein digestibility of distillers dried grains with solubles.

BACKGROUND: Distillers dried grains with solubles (DDGS) are rich in nutrition, and they are potential protein feed raw material. However, the existence of cellulose, hemicellulose and lignin hinders animals' digestion and absorption of DDGS. Making full use of unconventional feed resources such as DDGS can alleviate the shortage of feed resources to a certain extent. This research investigated the effects of twin-screw extrusion on the macromolecular composition, physical and chemical properties, surface structure and in vitro protein digestibility (IVPD) of DDGS. RESULTS: The findings showed that extrusion puffing significantly increased the protein solubility, bulk density, water holding capacity, and swelling capacity, while significantly decreased hemicellulose and crude protein content, particle size and zeta potential of DDGS. The structure damage of DDGS induced by the extrusion was characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FITR) spectroscopy and X-ray diffraction (XRD) analysis. Interestingly, no random coil was observed in the analysis of the secondary structure, and extrusion promoted the transformation of α-helix and ß-turn to ß-sheet, which led to significant increases in protein solubility and IVPD of DDGS (P < 0.05). Additionally, correlation analysis revealed that IVPD and PS had a positive relationship. CONCLUSION: Extrusion puffing was an ideal pretreatment method for DDGS modification to improve in vitro protein digestibility. © 2023 Society of Chemical Industry.

Enhancing pig growth and gut health with fermented Jatropha curcas cake: Impacts on microbiota, metabolites, and neurotransmitters.

Given the escalating global crisis in feed protein availability, Jatropha curcas L. cake has attracted significant interest as a viable alternative protein source in animal feed. This experiment was conducted to investigate the effects of fermented Jatropha curcas L. cake (FJCC) as a protein feed in the diet of pigs. A total of 96 growing pigs with an average weight of 27.60 ± 1.59 kg were divided into three dietary groups with varying FJCC inclusion levels (0, 2.5, and 5%) for a 28 d trial. Results showed that the diet with 5% FJCC (FJCC5) demonstrated significant improvements in average daily gain (p = 0.009), feed-to-gain ratio (p = 0.036), nutrient digestibility, and intestinal morphology. Furthermore, the FJCC5 diet resulted in a decrease in pH values in different gut sections (jejunum p = 0.045, cecum p = 0.001, colon p = 0.012), and favorably altered the profile of short-chain fatty acids (SCFAs) with increased butyric acid content (p = 0.005) and total SCFAs (p = 0.019). Additionally, this diet notably decreased IL-6 levels in the jejunum (p = 0.008) and colon (=0.047), significantly reduced IL-1 levels in the hypothalamus (p < 0.001), and lowered IL-1, IL-6, and IL-10 levels in plasma (p < 0.05). Microbiota and metabolite profile analysis revealed an elevated abundance of beneficial microbes (p < 0.05) and key metabolites such as 4-aminobutyric acid (GABA) (p = 0.003) and serotonin (5-HT) (p = 0.022), linked to neuroactive ligand-receptor interaction. Moreover, FJCC5 significantly boosted circulating neurotransmitter levels of 5-HT (p = 0.006) and GABA (p = 0.002) in plasma and hypothalamus, with corresponding increases in precursor amino acids (p < 0.05). These findings suggest that FJCC, particularly at a 5% inclusion rate, can be an effective substitute for traditional protein sources like soybean meal, offering benefits beyond growth enhancement to gut health and potentially impacting the gut-brain axis. This research underscores FJCC's potential as a valuable component in sustainable animal nutrition strategies.

Assessing the impact of occlusal plane rotation on facial aesthetics in orthodontic treatment: a machine learning approach.

BACKGROUND: Adequate occlusal plane (OP) rotation through orthodontic therapy enables satisfying profile improvements for patients who are disturbed by their maxillomandibular imbalance but reluctant to surgery. The study aims to quantify profile improvements that OP rotation could produce in orthodontic treatment and whether the efficacy differs among skeletal types via machine learning. MATERIALS AND METHODS: Cephalometric radiographs of 903 patients were marked and analyzed by trained orthodontists with assistance of Uceph, a commercial software which use artificial intelligence to perform the cephalometrics analysis. Back-propagation artificial neural network (BP-ANN) models were then trained based on collected samples to fit the relationship among maxillomandibular structural indicators, SN-OP and P-A Face Height ratio (FHR), Facial Angle (FA). After corroborating the precision and reliability of the models by T-test and Bland-Altman analysis, simulation strategy and matrix computation were combined to predict the consequent changes of FHR, FA to OP rotation. Linear regression and statistical approaches were then applied for coefficient calculation and differences comparison. RESULTS: The regression scores calculating the similarity between predicted and true values reached 0.916 and 0.908 in FHR, FA models respectively, and almost all pairs were in 95% CI of Bland-Altman analysis, confirming the effectiveness of our models. Matrix simulation was used to ascertain the efficacy of OP control in aesthetic improvements. Intriguingly, though FHR change rate appeared to be constant across groups, in FA models, hypodivergent group displayed more sensitive changes to SN-OP than normodivergent, hypodivergent group, and Class III group significantly showed larger changes than Class I and II. CONCLUSIONS: Rotation of OP could yield differently to facial aesthetic improvements as more efficient in hypodivergent groups vertically and Class III groups sagittally.

Tryptophan alleviates lipopolysaccharide-induced liver injury and inflammation by modulating necroptosis and pyroptosis signaling pathways in piglets.

The liver plays crucial roles in material metabolism and immune response. Bacterial endotoxin can cause various liver diseases, thereby causing significant economic losses to pig industry. Tryptophan is an essential amino acid in piglets. However, whether tryptophan can alleviate liver injury and inflammation by regulating necroptosis and pyroptosis has not been clarified. This study aimed to investigate whether dietary tryptophan can alleviate lipopolysaccharide (LPS)-induced liver injury in weaned piglets. 18 weaned piglets were randomly distributed to three treatments, each with 6 replicates: (1) control; (2) LPS-challenged control; (3) LPS + 0.2% tryptophan. After feeding with control or 0.2% tryptophan-supplemented diets for 35 d, pigs were intraperitoneally injected with saline or LPS (100 mg/kg body weight). At 4 h post-injection, blood samples and liver were collected. Results indicated that tryptophan reduced alanine aminotransferase, aspartate aminotransferase, decreased the mRNA expression and protein expression of 70-kDa heat shock proteins. Moreover, tryptophan increased the mRNA expression and protein expression of claudin-1, occludin and zonula occludens and decreased hydrogen peroxide and malondialdehyde contents, and increased catalase, glutathione peroxidase and total superoxide dismutase activities and proinflammatory cytokine levels in the liver. Meanwhile, tryptophan inhibited pyroptosis-related and necroptosis-related protein expression in liver. Collectively, tryptophan could relieve liver damage, increased the antioxidant capacity and reduced inflammation by inhibiting pyroptosis and necroptosis signaling pathways.

Tryptophan alleviates intestinal damage through regulating necroptosis and TLR4/NOD signaling pathways in pigs after lipopolysaccharide challenge.

This study aimed to test the hypothesis that necroptosis, toll-like receptor 4 (TLR4)/nucleotide-binding oligomerization domain (NOD) signaling pathway in the jejunum of lipopolysaccharide (LPS)-challenged piglets are involved in the alleviation of intestinal injury and inflammation by tryptophan supplementation. Tryptophan supplementation has improved intestinal morphology. Also, tryptophan has been found to increase the mRNA and protein expression of tight junction proteins and decrease the expression of pro-inflammatory cytokines. Dietary tryptophan decreased the mRNA expression of heat shock protein 70, TLR4, NOD1, NOD2, myeloid differentiation primary response gene 88, interleukin 1 receptor-associated kinase 1, TNF receptor-associated factor 6, receptor-interacting serine/threonine-protein kinase 2-like, nuclear factor-kappaB transcription factor P65 in the jejunum of piglets. Tryptophan alleviated LPS-induced necroptosis and decreased the mRNA expression of mixed lineage kinase domain-like, receptor-interacting serine/threonine kinase 1, receptor-interacting serine/threonine-protein kinase 3-like, Fas (TNFRSF6)-associated via death domain, PGAM family member 5. Collectively, our results suggest that tryptophan supplementation helps in the attenuation of intestinal injury and inflammation by alleviating necroptosis and TLR4/NOD in lipopolysaccharide-challenged pigs.

Hydroxy-Selenomethionine Mitigated Chronic Heat Stress-Induced Porcine Splenic Damage via Activation of Nrf2/Keap1 Signal and Suppression of NFκb and STAT Signal.

Chronic heat stress (CHS) compromised the immunity and spleen immunological function of pigs, which may associate with antioxidant suppression and splenocyte apoptosis and splenic inflammation. Selenium (Se) exhibited antioxidant function and immunomodulatory through selenoprotein. Thus, this study aimed to investigate the protective effect of dietary hydroxy-selenomethionine (Selisso®, SeO) on chronic heat stress (CHS)-induced porcine splenic oxidative stress, apoptosis and inflammation. Growing pigs were raised in the thermoneutral environment (22 ± 2 °C) with the basal diet (BD), or raised in hyperthermal conditions (33 ± 2 °C) with BD supplied with 0.0, 0.2, 0.4 and 0.6 mg Se/kg SeO for 28 d, respectively. The results showed that dietary SeO supplementation recovered the spleen mass and enhanced the splenic antioxidant capacity of CHS growing pigs. Meanwhile, SeO activated the Nrf2/Keap1 signal, downregulated p38, caspase 3 and Bax, inhibited the activation of NFκb and STAT3, and enhanced the protein expression level of GPX1, GPX3, GPX4, SELENOS and SELENOF. In summary, SeO supplementation mitigates the CHS-induced splenic oxidative damages, apoptosis and inflammation in pigs, and the processes are associated with the activation of Nrf2/Keap1 signal and the suppression of NFκb, p38(MAPK) and STAT signal. It seems that the antioxidant-related selenoproteins (GPXs) and functional selenoproteins (SELENOS and SELENOF) play important roles in the alleviation processes.

Different Dietary Sources of Selenium Alleviate Hepatic Lipid Metabolism Disorder of Heat-Stressed Broilers by Relieving Endoplasmic Reticulum Stress.

As global warming continues, the phenomenon of heat stress (HS) in broilers occurs frequently. The alleviating effect of different selenium (Se) sources on HS-induced hepatic lipid metabolism disorders in broilers remains unclear. This study compared the protective effects of four Se sources (sodium selenite; selenium yeast; selenomethionine; nano-Se) on HS-induced hepatic lipid metabolism disorder and the corresponding response of selenotranscriptome in the liver of broilers. The results showed that HS-induced liver injury and hepatic lipid metabolism disorder, which were reflected in the increased activity of serum alanine aminotransferase (ALT), the increased concentration of triacylglycerol (TG) and total cholesterol (TC), the increased activity of acetyl-CoA carboxylase (ACC), diacylglycerol O-acyltransferase (DGAT) and fatty acid synthase (FAS), and the decreased activity of hepatic lipase (HL) in the liver. The hepatic lipid metabolism disorder was accompanied by the increased mRNA expression of lipid synthesis related-genes, the decreased expression of lipidolysis-related genes, and the increased expression of endoplasmic reticulum (ER) stress biomarkers (PERK, IRE1, ATF6, GRP78). The dietary supplementation of four Se sources exhibited similar protective effects. Four Se sources increased liver Se concentration and promoted the expression of selenotranscriptome and several key selenoproteins, enhanced liver antioxidant capacity and alleviated HS-induced ER stress, and thus resisted the hepatic lipid metabolism disorders of broilers exposed to HS. In conclusion, dietary supplementation of four Se sources (0.3 mg/kg) exhibited similar protective effects on HS-induced hepatic lipid metabolism disorders of broilers, and the protective effect is connected to the relieving of ER stress.

Effect of dietary licorice flavonoids powder on performance, intestinal immunity and health of weaned piglets.

Licorice flavonoids, a bioactive substance derived from glycyrrhiza, have been reported for many pharmacological properties and are beneficial to animal health. This study aimed to explore the effects of licorice flavonoids powder (LFP) on growth performance and intestinal health of piglets. A total of 96 weaned piglets were randomly assigned into four treatments and supplemented with 0, 50, 150 and 250 mg/kg LFP for 5 weeks. Dietary LFP supplementation tended to increase (p = 0.068) average daily gain (ADG) and reduce (p = 0.089) the feed intake/body gain (F/G) of piglets than that of the control group during 15-35 days; and concentrations of LFP supplementation reduced (p < 0.01) diarrhoea index during 14-35 days and 0-35 days. Piglets fed on diets supplied with LFP had a lower (p < 0.05) pH in caecum and colon. Dietary LFP supplementation increased (p < 0.01) the villi height and the ratio of villi height/crypt depth in duodenum, and reduced (p < 0.05) crypt depth in duodenum. Compared with the control group, 250 mg/kg LFP supplementation up-regulated (p < 0.05) the mRNA level of occludin (OCLN) in ileum. Meanwhile, dietary LFP supplementation down-regulated (p < 0.05) mRNA abundance of Interleukin (IL)-1ß, IL-8 and induced nitrogen monoxide synthase (INOS) in duodenum. Dietary 150 mg/kg LFP supplementation down-regulated (p < 0.05) mRNA abundance of IL-1ß and 250 mg/kg LFP up-regulated (p < 0.05) the expression of IL-10 in ileum. In summary, dietary LFP supplementation has a trend to improve the performance of weaning piglets, those improvements are accompanied by reduction in diarrhoea, enhancement of intestinal morphological structure, barrier function, immune function, and development. In general, 150 mg/kg LFP supplementation is more effective.

Predicting Nash equilibria for microbial metabolic interactions.

MOTIVATION: Microbial metabolic interactions impact ecosystems, human health and biotechnology profoundly. However, their determination remains elusive, invoking an urgent need for predictive models seamlessly integrating metabolism with evolutionary principles that shape community interactions. RESULTS: Inspired by the evolutionary game theory, we formulated a bi-level optimization framework termed NECom for which any feasible solutions are Nash equilibria of microbial community metabolic models with/without an outer-level (community) objective function. Distinct from discrete matrix games, NECom models the continuous interdependent strategy space of metabolic fluxes. We showed that NECom successfully predicted several classical games in the context of metabolic interactions that were falsely or incompletely predicted by existing methods, including prisoner's dilemma, snowdrift and cooperation. The improved capability originates from the novel formulation to prevent 'forced altruism' hidden in previous static algorithms while allowing for sensing all potential metabolite exchanges to determine evolutionarily favorable interactions between members, a feature missing in dynamic methods. The results provided insights into why mutualism is favorable despite seemingly costly cross-feeding metabolites and demonstrated similarities and differences between games in the continuous metabolic flux space and matrix games. NECom was then applied to a reported algae-yeast co-culture system that shares typical cross-feeding features of lichen, a model system of mutualism. 488 growth conditions corresponding to 3221 experimental data points were simulated. Without training any parameters using the data, NECom is more predictive of species' growth rates given uptake rates compared with flux balance analysis with an overall 63.5% and 81.7% reduction in root-mean-square error for the two species respectively. AVAILABILITY AND IMPLEMENTATION: Simulation code and data are available at https://github.com/Jingyi-Cai/NECom.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Spectrophotometric Detection of the BRCA1 Gene via Exponential Isothermal Amplification and Hybridization Chain Reaction of Surface-Bound Probes.

In this work, we demonstrated an ultrasensitive approach with a dual-amplification strategy for DNA assay based on isothermal exponential amplification (EXPAR) and the hybridization chain reaction (HCR). In the presence of target DNA, the hairpin probe DNA (HP1) recognized and partially hybridized with the target DNA to form double-stranded structures containing the full recognition sequences for nicking endonuclease and then initiated EXPAR. Under the reaction of EXPAR, a large number of single-stranded DNA (ssDNA) was produced in the circle of nicking, polymerization, and strand displacement. The resulting ssDNA can bind to the surface-bound probe on the well of the microplate and trigger the hybridization chain reaction, resulting in the production of numerous double-stranded DNA concatamers with biotin labeling. In the presence of streptavidin-conjugated horseradish peroxidase (HRP), the amplified signal can be detected by a spectrophotometer via HRP-catalyzed substrate 3,3'5,5'-tetramethylbenzidine (TMB). This proposed dual-amplification method provides a detection limit of 74.48 aM, which also exhibits good linearity ranging from 0.1 fM to 100 pM.

Rapid detoxification of Jatropha curcas cake by fermentation with a combination of three microbial strains and characterization of their metabolic profiles.

AIM: Our previous study reported a strain that can detoxify Jatropha curcas L. cake (JCC), but the detoxification duration is long. This study intends to explore the efficient detoxification of JCC through multi-strain collaborative fermentation to accelerate the detoxification process. METHODS AND RESULTS: Mucor circinelloides SCYA25 strain that we previously reported can effectively degrade the toxicity of JCC, and the newly screened Bacillus megaterium SCYA10 and Geotrichum candidum SCYA23 strains were used to detoxify JCC. Different solid-state-fermentation (SSF) parameters were optimized by single-factor tests and response surface methodology. A detoxification rate established by zebrafish toxicity of JCC at 96% was achieved under the following optimized conditions: the combination ratio of B. megaterium SCYA10, G. candidum SCYA23 and M. circinelloides SCYA25 at 2:3:1, a total injection amount of 15.25%, a feed to water ratio of 1:0.68, a fermentation temperature of 30.3°C and fermentation duration of 21.5 days. The protein content of fermented JCC (FJCC) increased, while the concentrations of ether extract, crude fibre and toxins were all degraded considerably. Metabolomics analysis revealed that the fermentation increased the contents of neurotransmitter receptor modulator, emulsifier, aromatic substances and insecticidal compounds, as well as decreasing the contents of oxidative stress and neurotoxic substances. A rat feeding trial showed that the growth performance of the rats provided with the FJCC diet was similar to that of the corn-soybean meal group, and no lesions in the liver and kidney were observed. CONCLUSION: The co-bio-fermentation process can effectively detoxify JCC and improve its nutritional value, which means it could be served as a protein feed in animal husbandry. SIGNIFICANCE: The combination of three microbial strains can detoxify JCC in a safe and effective manner to provide a great potential alternative to soybean meal. The research also suggests that metabonomics and bioinformatics are useful tools for revealing the bio-detoxification mechanism.

Selenium exerts protective effects against heat stress-induced barrier disruption and inflammation response in jejunum of growing pigs.

BACKGROUND: Heat stress (HS) has a negative impact on the intestinal barrier and immune function of pigs. Selenium (Se) may improve intestinal health through affecting selenoproteins. Thus we investigate the protective effect of new organic Se (2-hydroxy-4-methylselenobutanoic acid, HMSeBA) on jejunal damage in growing pigs upon HS and integrate potential roles of corresponding selenoproteins. RESULTS: HS decreased the villus height and increased (P < 0.05) the protein abundance of HSP70, and downregulated (P < 0.05) protein levels of tight junction-related proteins (CLDN-1 and OCLD). HS-induced jejunal damage was associated with the upregulation of four inflammation-related genes and ten selenoprotein-encoding genes, downregulation (P < 0.05) of four selenoprotein-encoding genes and decreased (P < 0.05) the protein abundance of GPX4 and SELENOS. Compared with the HS group, HMSeBA supplementation not only elevated the villus height and the ratio of V/C (P < 0:05), but also reduced (P < 0.05) the protein abundance of HSP70 and MDA content, and increased (P < 0.05) the protein abundance of OCLD. HMSeBA supplementation downregulated the expression of seven inflammation-related genes, changed the expression of 12 selenoprotein-encoding genes in jejunum mucosa affected by HS, and increased the protein abundance of GPX4, TXNRD1 and SELENOS. CONCLUSION: Organic Se supplementation beyond nutritional requirement alleviates the negative effect of HS on the jejunum of growing pigs, and its protective effect is related to the response of corresponding selenoproteins. © 2021 Society of Chemical Industry.

Glucagon-like peptide 2 attenuates intestinal mucosal barrier injury through the MLCK/pMLC signaling pathway in a piglet model.

Glucagon-like peptide-2 (GLP-2), an intestinotrophic hormone, has drawn considerable attention worldwide due to its potential to promote intestinal development. We investigated the effects and mechanisms of GLP-2 against lipopolysaccharide (LPS)-induced intestinal inflammation and injury both in vitro and in vivo. Forty healthy piglets weaned at the age of 28 days with similar body weight (BW) were assigned to four in vivo treatments with ten piglets each: (i) nonchallenged control; (ii) LPS-challenged control; (iii) LPS + low dose GLP-2; and (iv) LPS + high dose GLP-2. Piglets were subcutaneously injected with phosphate-buffered saline supplemented with GLP-2 at doses of 0, 0, 2, and 10 nmol/kg BW per day for seven consecutive days. The piglets were challenged with an intraperitoneal injection with 100 µg/kg LPS on day 14 to induce intestinal damage. After that, the gene and protein expression levels of representative tight junction proteins and myosin light-chain kinase (MLCK)/phosphorylated myosin light chain (pMLC), as well as proinflammatory cytokine levels were determined using quantitative reverse transcription polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay methods. A high dose of GLP-2 pretreatment increased intestinal permeability by downregulating and redistributing tight junction proteins (p < .05), for example, zona occluden-1 (ZO-1) and occludin. GLP-2 decreased the transcription of proinflammatory cytokines genes including interleukin-1ß (IL-1ß), IL-6, IL-8, and tumor necrosis factor-α in small intestines (p < .05). GLP-2 prevented the LPS-induced increase in the expression of MLCK dose-dependently and the increase in pMLC levels in the duodenum, jejunum, and ileum. To assess further the protective effect of GLP-2 on LPS-induced intestinal barrier injury after weaning and its possible mechanism, an in vitro intestinal epithelial barrier model was established with IPEC-J2 monolayers and treated with 100 µg/ml LPS with or without 1 × 10-8 mol/L GLP-2 pretreatment. The in vitro analysis included control, LPS, and GLP-2 + LPS treatments. GLP-2 treatment alleviated the destructive effect of LPS on barrier permeability by restoring the expression and ultrastructure of ZO-1 and occludin (p < .05). In addition, GLP-2 reversed the LPS-induced MLCK hyperexpression and pMLC hyperphosphorylation (p < .05). Taken together, our findings revealed a mechanism by which GLP-2 alleviated LPS-challenged intestinal barrier injury and inflammation in weaned piglets and IPEC-J2 cells via the MLCK/pMLC signaling pathway.

Integrating thermodynamic and enzymatic constraints into genome-scale metabolic models.

Stoichiometric genome-scale metabolic network models (GEMs) have been widely used to predict metabolic phenotypes. In addition to stoichiometric ratios, other constraints such as enzyme availability and thermodynamic feasibility can also limit the phenotype solution space. Extended GEM models considering either enzymatic or thermodynamic constraints have been shown to improve prediction accuracy. In this paper, we propose a novel method that integrates both enzymatic and thermodynamic constraints in a single Pyomo modeling framework (ETGEMs). We applied this method to construct the EcoETM (E. coli metabolic model with enzymatic and thermodynamic constraints). Using this model, we calculated the optimal pathways for cellular growth and the production of 22 metabolites. When comparing the results with those of iML1515 and models with one of the two constraints, we observed that many thermodynamically unfavorable and/or high enzyme cost pathways were excluded from EcoETM. For example, the synthesis pathway of carbamoyl-phosphate (Cbp) from iML1515 is both thermodynamically unfavorable and enzymatically costly. After introducing the new constraints, the production pathways and yields of several Cbp-derived products (e.g. L-arginine, orotate) calculated using EcoETM were more realistic. The results of this study demonstrate the great application potential of metabolic models with multiple constraints for pathway analysis and phenotype prediction.

Long non-coding RNA expression profiles in neutrophils revealed potential biomarker for prediction of renal involvement in SLE patients.

OBJECTIVE: The long non-coding RNA plays an important role in inflammation and autoimmune diseases. The aim of this study is to screen and identify abnormally expressed lncRNAs in peripheral blood neutrophils of SLE patients as novel biomarkers and to explore the relationship between lncRNAs levels and clinical features, disease activity and organ damage. METHODS: RNA-seq technology was used to screen differentially expressed lncRNAs in neutrophils from SLE patients and healthy donors. Based on the results of screening, candidate lncRNA levels in neutrophils of 88 SLE patients, 35 other connective disease controls, and 78 healthy controls were qualified by real-time quantitative polymerase chain reaction. RESULTS: LncRNA expression profiling revealed 360 up-regulated lncRNAs and 224 down-regulated lncRNAs in neutrophils of SLE patients when compared with healthy controls. qPCR assay validated that the expression of Lnc-FOSB-1:1 was significantly decreased in neutrophils of SLE patients when compared with other CTD patients or healthy controls. It correlated negatively with SLE Disease Activity Index 2000 (SLEDAI-2K) score (r = -0.541, P < 0.001) and IFN scores (r = -0.337, P = 0.001). More importantly, decreased Lnc-FOSB-1:1 expression was associated with lupus nephritis. Lower baseline Lnc-FOSB-1:1 level was associated with higher risk of future renal involvement (within an average of 2.6 years) in patients without renal disease at baseline (P = 0.019). CONCLUSION: LncRNA expression profile in neutrophils of SLE patients revealed differentially expressed lncRNAs. Validation study on Lnc-FOSB-1:1 suggest that it is a potential biomarker for prediction of near future renal involvement.

Designed Construction of SrTiO3 /SrSO4 /Pt Heterojunctions with Boosted Photocatalytic H2 Evolution Activity.

Efficient separation of photogenerated electron-hole pairs is a crucial factor for high-performance photocatalysts. Effective electron-hole separation and migration could be achieved by heterojunctions with suitable band structures. Herein, a porous SrTiO3 /SrSO4 heterojunction is prepared by a sol-gel method at room temperature followed by an annealing process. XRD characterization suggests high crystallinity of the heterostructure. A well-defined interface between the two phases is confirmed by high-resolution (HR)TEM. The photocatalytic H2 evolution productivity of the SrTiO3 /SrSO4 heterojunction with Pt as co-catalyst reaches 396.82 µmol g-1 h-1 , which is 16 times higher than that of SrTiO3 /Pt. The boosted photocatalytic activity of SrTiO3 /SrSO4 /Pt can be ascribed to the presence of SrSO4 , which promotes the transfer and migration of photogenerated carriers by forming the heterojunction and porous structure, which provides a large amount of active sites. This novel porous heterostructure brings new ideas for the development of high-efficiency photocatalysts for H2 release.

Selenium alleviates the negative effect of heat stress on myogenic differentiation of C2C12 cells with the response of selenogenome.

With the globe warming, heat stress (HS) has frequently affected animal production. Selenium (Se) is an essential trace element for animals and exerts most of its biological functions through selenoproteins. We previously demonstrated that the damage to C2C12 cells by HS accompanied with the response of selenoprotein encoding genes and proteins. The objective of this study was to investigate whether selenium supplementation (sodium selenite, SS and selenomethionine, SeMet) could alleviate the negative effect of heat stress on the differentiation of C2C12 cells, and interpret the potential corresponding selenoproteins response. The differentiated cells were cultured for 4 and 8 days under different condition: at 37 °C, 41.5 °C and 41.5 °C with 0.5 µmol Se/L SS or SeMet, and the HSP70, cell apoptosis, selenoproteins and cell differentiation-related gene or protein were detected. The result showed that HS up-regulated (P < 0.05) mRNA and protein levels of HSP70 and gene expression of AMPKα1 and AMPKα2, and down-regulated (P < 0.05) mRNA or protein levels of MYOGENIN and MYOD. Meanwhile, up to 15 and 17 selenoprotein genes expression were significantly changed response to 4-and 8-days HS challenge, respectively. Relative to the HS group, SS and SeMet supplementation down-regulated the mRNA and protein abundance of HSP70 to different degrees, and partly recovered (P < 0.05) the mRNA or protein abundance of MYOGENIN and MYOD at 4th and 8th day. Especially, 16 and 10 selenoprotein genes expression in cells affected by HS were altered by SS and SeMet supplementation, respectively. Both SS and SeMet supplementation modestly increased (P < 0.05) protein levels of GPX1 and SELENON in cells under HS. In summary, Se supplementation partly alleviated the negative impact of HS on myogenic differentiation of C2C12 cells and the process may associate with the alternation of selenoprotein expression pattern, and SeMet exhibits better effect than SS.

Zirconia Hybrid Nanoshells for Nutrient and Toxin Detection.

Monitoring milk quality is of fundamental importance in food industry, because of the nutritional value and resulting position of milk in daily diet. The detection of small nutrients and toxins in milk is challenging, considering high sample complexity and low analyte abundance. In addition, the slow analysis and tedious sample preparation hinder the large-scale application of conventional detection techniques. Herein, zirconia hybrid nanoshells are constructed to enhance the performance of laser desorption/ionization mass spectrometry (LDI MS). Zirconia nanoshells with the optimized structures and compositions are used as matrices in LDI MS and achieve direct analysis of small molecules from 5 nL of native milk in ≈1 min, without any purification or separation. Accurate quantitation of small nutrient is achieved by introducing isotope into the zirconia nanoshell-assisted LDI MS as the internal standard, offering good consistency to biochemical analysis (BCA) with R2  = 0.94. Further, trace toxin is enriched and identified with limit-of-detection (LOD) down to 4 pm, outperforming the current analytical methods. This work sheds light on the personalized design of material-based tool for real-case bioanalysis and opens up new opportunities for the simple, fast, and cost-effective detection of various small molecules in a broad field.

Symptom continuum reported by affective disorder patients through a structure-validated questionnaire.

BACKGROUND: Affective disorders, such as major depressive (MDD), bipolar I (BD I) and II (BD II) disorders, are overlapped at a continuum, but their exact loci are not clear. The self-reports from patients with affective disorders might help to clarify this issue. METHODS: We invited 738 healthy volunteers, 207 individuals with BD I, 265 BD II, and 192 MDD to answer a 79 item-MATRIX about on-going affective states. RESULTS: In study 1, all 1402 participants were divided random-evenly and gender-balanced into two subsamples; one subsample was used for exploratory factor analysis, and another for confirmatory factor analysis. A structure-validated inventory with six domains of Overactivation, Psychomotor Acceleration, Distraction/ Impulsivity, Hopelessness, Retardation, and Suicide Tendency, was developed. In study 2, among the four groups, MDD scored the highest on Retardation, Hopelessness and Suicide Tendency, whereas BD I on Distraction/ Impulsivity and Overactivation. CONCLUSION: Our patients confirmed the affective continuum from Suicide Tendency to Overactivation, and described the different loci of MDD, BD I and BD II on this continuum.