Enhancing psychiatric rehabilitation outcomes through a multimodal multitask learning model based on BERT and TabNet: An approach for personalized treatment and improved decision-making.

Evaluating the rehabilitation status of individuals with serious mental illnesses (SMI) necessitates a comprehensive analysis of multimodal data, including unstructured text records and structured diagnostic data. However, progress in the effective assessment of rehabilitation status remains limited. Our study develops a deep learning model integrating Bidirectional Encoder Representations from Transformers (BERT) and TabNet through a late fusion strategy to enhance rehabilitation prediction, including referral risk, dangerous behaviors, self-awareness, and medication adherence, in patients with SMI. BERT processes unstructured textual data, such as doctor's notes, whereas TabNet manages structured diagnostic information. The model's interpretability function serves to assist healthcare professionals in understanding the model's predictive decisions, improving patient care. Our model exhibited excellent predictive performance for all four tasks, with an accuracy exceeding 0.78 and an area under the curve of 0.70. In addition, a series of tests proved the model's robustness, fairness, and interpretability. This study combines multimodal and multitask learning strategies into a model and applies it to rehabilitation assessment tasks, offering a promising new tool that can be seamlessly integrated with the clinical workflow to support the provision of optimized patient care.

Employing graph attention networks to decode psycho-metabolic interactions in Schizophrenia.

Schizophrenia is a severe mental disorder characterized by intricate and underexplored interactions between psychological symptoms and metabolic health, presenting challenges in understanding the disease mechanisms and designing effective treatment strategies. To delve deeply into the complex interactions between mental and metabolic health in patients with schizophrenia, this study constructed a psycho-metabolic interaction network and optimized the Graph Attention Network (GAT). This approach reveals complex data patterns that traditional statistical analyses fail to capture. The results show that weight management and medication management play a central role in the interplay between psychiatric disorders and metabolic health. Furthermore, additional analysis revealed significant correlations between the history of psychiatric symptoms and physical health indicators, as well as the key roles of biochemical markers(e.g., triglycerides and low-density lipoprotein cholesterol), which have not been sufficiently emphasized in previous studies. This highlights the importance of medication management approaches, weight management, psychological treatment, and biomarker monitoring in comprehensive treatment and underscores the significance of the biopsychosocial model. This study is the first to utilize a GNN to explore the interactions between schizophrenia symptoms and metabolic features, providing new insights into understanding psychiatric disorders and guiding the development of more comprehensive treatment strategies for schizophrenia.

A NiMOF integrated with conductive materials for efficient bifunctional electrocatalysis of urea oxidation and oxygen evolution reactions.

The development of urea oxidation reaction (UOR) and oxygen evolution reaction (OER) bifunctional electrocatalysts has dual significance in promoting hydrogen energy production and urea-rich wastewater treatment. Herein, a carboxylated multi-walled carbon nanotube (MWCNT-COOH)-ferrocene carboxylic acid (Fc-COOH) modulated NiMOF hybrid material (MWCNT-NiMOF(Fc)) has been synthesized for dual electrocatalysis of the UOR and OER. The material characterization results indicated that MWCNT-COOH and Fc-COOH were integrated into the framework structure of the NiMOF. The direct interaction between the NiMOF and MWCNT/Fc facilitated electron transfer in the hybrid material and led to lattice strain, which improved the charge transfer kinetics, promoted the exposure of more unsaturated Ni sites, and increased the electrochemically active surface area. These factors together enhanced the electrocatalytic activity of MWCNT-NiMOF(Fc) towards the UOR and OER. Using a glassy carbon electrode as the substrate, MWCNT-NiMOF(Fc) exhibited low potential requirements, low Tafel slopes, and high stability. In overall urea and water splitting electrolysis cells, the excellent UOR and OER dual functional catalytic ability and enormous practical application potential of the MWCNT-NiMOF(Fc) modified foam nickel electrode were further demonstrated. On the basis of the above research, the influence of a KOH environment on urea electrolysis was further studied, and the urea electrolysis products were analyzed, promoting a more comprehensive understanding of the catalytic performance of MWCNT-NiMOF(Fc) for urea oxidation. This study provides a new approach for developing high-performance NiMOF-based electrocatalysts for challenging bifunctional UOR/OER applications, and has potential application value in hydrogen production from urea-containing wastewater electrolysis.

Effects of Different Forms and Proportions of Nitrogen on the Growth, Photosynthetic Characteristics, and Carbon and Nitrogen Metabolism in Tomato.

Optimal plant growth in many species is achieved when the two major forms of N are supplied at a particular ratio. This study investigated optimal nitrogen forms and ratios for tomato growth using the 'Jingfan 502' tomato variety. Thirteen treatments were applied with varying proportions of nitrate nitrogen (NN), ammonium nitrogen (AN), and urea nitrogen (UN). Results revealed that the combination of AN and UN inhibited tomato growth and photosynthetic capacity. Conversely, the joint application of NN and UN or NN and AN led to a significant enhancement in tomato plant growth. Notably, the T12 (75%UN:25%NN) and T4 (75%NN:25%AN) treatments significantly increased the gas exchange and chlorophyll fluorescence parameters, thereby promoting the accumulation of photosynthetic products. The contents of fructose, glucose, and sucrose were significantly increased by 121.07%, 206.26%, and 94.64% and by 104.39%, 156.42%, and 61.40%, respectively, compared with those in the control. Additionally, AN favored starch accumulation, while NN and UN favored fructose, sucrose, and glucose accumulation. Gene expression related to nitrogen and sugar metabolism increased significantly in T12 and T4, with T12 showing greater upregulation. Key enzyme activity in metabolism also increased notably. In summary, T12 enhanced tomato growth by upregulating gene expression, increasing enzyme activity, and boosting photosynthesis and sugar accumulation. Growers should consider using NN and UN to reduce AN application in tomato fertilization.

Physiological responses of coriander (Coriandrum sativum L.) to exogenous 2,4-epibrassinolide at different concentrations.

BACKGROUND: Brassinolide, known as the seventh plant hormone, can improve the photosynthetic capacity of plants, promote plant growth and development, promote the formation of horticultural crop yield, improve the quality of horticultural crops, and also improve the ability of plants to resist biological and abiotic stresses. RESULTS: The effects of different concentrations of exogenously sprayed 2,4-epibrassinolide (EBR) on growth, physiological and photosynthetic characteristics of 'All-round large leaf coriander' were studied in substrate culture. The results showed that 0.05, 0.1, and 0.5 mg.L- 1 EBR promoted the growth of coriander and increased the aboveground fresh and dry weights, with 0.5 mg.L- 1 EBR having the most significant effect. Spraying 0.1 mg.L- 1 EBR increased the content of soluble sugars and protein of coriander leaves. Spraying 0.1 and 0.5 mg.L- 1 EBR significantly increased the chlorophyll content and photosynthetic parameters of coriander leaves, and 0.5 mg.L- 1 EBR also significantly increased the chlorophyll fluorescence parameters of coriander leaves. Spraying 0.5 mg.L- 1 EBR upregulated the expression of CsRbcS, CsFBPase, and CsAld. Correlation analysis showed that aboveground fresh weight under exogenous EBR treatment was significantly positively correlated with aboveground dry weight, plant height, Pn, Gs, Ci, and CsAld (P < 0.05), and soluble sugar content was significantly positively correlated with the number of leaves, Y(II), qP, and CsRbcS. The results of the principal component analysis (PCA) showed that there was a significant separation between the treatment and the control groups. Spraying 0.5 mg.L- 1 EBR can promote the growth of coriander, improve the quality of coriander leaves, and strengthen coriander leaf photosynthetic capacity. This study provides new insights into the promotion of coriander growth and development following the application of exogenous EBR. CONCLUSION: Exogenous EBR treatment increased coriander plant height, leaf growth and aboveground dry weight, and enhanced photosynthesis. Exogenous spraying of 0.5 mg.L- 1 EBR had the most significant effect.

Controlling water deficiency as an abiotic stress factor to improve tomato nutritional and flavour quality.

Water deficit (WD) irrigation techniques to improve water use efficiency have been rapidly developed. However, the effect of WD irrigation on tomato quality has not been sufficiently studied. Here, we investigated the effects of varying water irrigation levels [T1-T4: 80%, 65%, 55%, and 45% of maximum field moisture capacity (FMC)] and full irrigation (CK: 90% of maximum FMC) on tomato fruits from the mature-green to red-ripening stages, to compare the nutritional and flavour qualities of the resulting tomatoes. The proline, aspartic, malic, citric, and ascorbic acid contents increased, phenylalanine and glutamic acid contents decreased, and the total amino and organic acid contents increased by 18.91% and 26.12%, respectively, in T2-treated fruits. Furthermore, the T2-treated fruits exhibited higher K and P contents alongside improved characteristic aromas. These findings provide novel insights for further improvements in tomato quality while also developing water-saving irrigation techniques.

Assessing future heat stress across China: combined effects of heat and relative humidity on mortality.

This study utilizes China's records of non-accidental mortality along with twenty-five simulations from the NASA Earth Exchange Global Daily Downscaled Projections to evaluate forthcoming heat stress and heat-related mortality across China across four distinct scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The findings demonstrate a projected escalation in the heat stress index (HSI) throughout China from 2031 to 2100. The most substantial increments compared to the baseline (1995-2014) are observed under SSP5-8.5, indicating a rise of 7.96°C by the year 2100, while under SSP1-2.6, the increase is relatively modest at 1.54°C. Disparities in HSI growth are evident among different subregions, with South China encountering the most significant elevation, whereas Northwest China exhibits the lowest increment. Projected future temperatures align closely with HSI patterns, while relative humidity is anticipated to decrease across the majority of areas. The study's projections indicate that China's heat-related mortality is poised to surpass present levels over the forthcoming decades, spanning a range from 215% to 380% from 2031 to 2100. Notably, higher emission scenarios correspond to heightened heat-related mortality. Additionally, the investigation delves into the respective contributions of humidity and temperature to shifts in heat-related mortality. At present, humidity exerts a greater impact on fluctuations in heat-related mortality within China and its subregions. However, with the projected increase in emissions and global warming, temperature is expected to assume a dominant role in shaping these outcomes. In summary, this study underscores the anticipated escalation of heat stress and heat-related mortality across China in the future. It highlights the imperative of emission reduction as a means to mitigate these risks and underscores the variances in susceptibility to heat stress across different regions.

Integrated analysis of SKA1-related ceRNA network and SKA1 immunoassays in HCC: A study based on bioinformatic.

Hepatocellular carcinoma (HCC) poses a global health challenge. Effective biomarkers are required for early diagnosis to improve survival rates of patients with HCC. Spindle and kinetochore-associated complex subunits 1 (SKA1) is essential for proper chromosome segregation in the mitotic cell cycle. Previous studies have shown that overexpression of SKA1 is associated with a poor prognosis in various cancers. The expression, prognostic value, and clinical functions of SKA1 in HCC were evaluated with several bioinformatics web portals. Additionally, we identified target long non-coding RNAs (lncRNAs) and microRNAs by analyzing messenger RNA (mRNA)-miRNA and miRNA-lncRNA interaction data and elucidated the potential competing endogenous RNA (ceRNA) mechanism associated with SKA1. High SKA1 expression was associated with poor prognosis in patients with HCC. Furthermore, multivariate Cox regression analysis revealed that SKA1 expression was an independent prognostic factor for HCC. GO and KEGG analyses showed that SKA1 is related to the cell cycle checkpoints, DNA replication and repair, Rho GTPases signaling, mitotic prometaphase, and kinesins. Gene set enrichment analysis revealed that high levels of SKA1 are associated with cancer-promoting pathways. DNA methylation of SKA1 in HCC tissues was lower than that in normal tissues. Ultimately, the following 9 potential ceRNA-based pathways targeting SKA1 were identified: lncRNA: AC026401.3, Small Nucleolar RNA Host Gene 3 (SNHG3), and AC124798.1-miR-139-5p-SKA1; lncRNA: AC26356.1, Small Nucleolar RNA Host Gene 16 (SNHG16), and FGD5 Antisense RNA 1-miR-22-3p-SKA1; lncRNA: Cytoskeleton Regulator RNA (CYTOR), MIR4435-2 Host Gene, and differentiation antagonizing non-protein coding RNA-miR-125b-5p-SKA1. SKA1 expression levels significantly correlated with immune cell infiltration and immune checkpoint genes in the HCC tissues. SKA1 is a potential prognostic biomarker for HCC. This study provides a meaningful direction for research on SKA1-related mechanisms, which will be beneficial for future research on HCC-related molecular biological therapies and targeted immunotherapy.

Application of Exogenous Silicon for Alleviating Photosynthetic Inhibition in Tomato Seedlings under Low-Calcium Stress.

To address the low Ca-induced growth inhibition of tomato plants, the mitigation effect of exogenous Si on tomato seedlings under low-Ca stress was investigated using different application methods. We specifically analyzed the effects of root application or foliar spraying of 1 mM Si on growth conditions, leaf photosynthetic properties, stomatal status, chlorophyll content, chlorophyll fluorescence, ATP activity and content, Calvin cycle-related enzymatic activity, and gene expression in tomato seedlings under low vs. adequate calcium conditions. We found that the low-Ca environment significantly affected (reduced) these parameters, resulting in growth limitation. Surprisingly, the application of 1 mM Si significantly increased plant height, stem diameter, and biomass accumulation, protected photosynthetic pigments, improved gas exchange, promoted ATP production, enhanced the activity of Calvin cycle key enzymes and expression of related genes, and ensured efficient photosynthesis to occur in plants under low-Ca conditions. Interestingly, when the same amount of Si was applied, the beneficial effects of Si were more pronounced under low-Ca conditions that under adequate Ca. We speculate that Si might promote the absorption and transport of calcium in plants. The effects of Si also differed depending on the application method; foliar spraying was better in alleviating photosynthetic inhibition in plants under low-Ca stress, whereas root application of Si significantly promoted root growth and development. Enhancing the photosynthetic capacity by foliar Si application is an effective strategy for ameliorating the growth inhibition of plants under low-Ca stress.

Ligand-independent integrin ß1 signaling supports lung adenocarcinoma development.

Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that the highly expressed integrin ß1 subunit is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin ß1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin ß1-mediated adhesion to ECM but are dependent on integrin ß1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). These studies support a critical role for integrin ß1 in lung tumorigenesis that is mediated through constitutive, ECM binding-independent signaling involving the cytoplasmic tail.

Hyperlipidemic hypersensitivity to lethal microbial inflammation and its reversal by selective targeting of nuclear transport shuttles.

Hyperlipidemia, the hallmark of Metabolic Syndrome that afflicts millions of people worldwide, exacerbates life-threatening infections. We present a new evidence for the mechanism of hyperlipidemic hypersensitivity to microbial inflammation caused by pathogen-derived inducer, LPS. We demonstrate that hyperlipidemic animals succumbed to a non-lethal dose of LPS whereas normolipidemic controls survived. Strikingly, survival of hyperlipidemic animals was restored when the nuclear import of stress-responsive transcription factors (SRTFs), Sterol Regulatory Element-Binding Proteins (SREBPs), and Carbohydrate-Responsive Element-Binding Proteins (ChREBPs) was impeded by targeting the nuclear transport checkpoint with cell-penetrating, biselective nuclear transport modifier (NTM) peptide. Furthermore, the burst of proinflammatory cytokines and chemokines, microvascular endothelial injury in the liver, lungs, heart, and kidneys, and trafficking of inflammatory cells were also suppressed. To dissect the role of nuclear transport signaling pathways we designed and developed importin-selective NTM peptides. Selective targeting of the importin α5, ferrying SRTFs and ChREBPs, protected 70-100% hyperlipidemic animals. Targeting importin ß1, that transports SREBPs, was only effective after 3-week treatment that lowered blood triglycerides, cholesterol, glucose, and averted fatty liver. Thus, the mechanism of hyperlipidemic hypersensitivity to lethal microbial inflammation depends on metabolic and proinflammatory transcription factors mobilization, which can be counteracted by targeting the nuclear transport checkpoint.

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In order to realize precise fertilization and high yield management of Pinus massoniana clonal seed orchard, clones with different fruiting abilities were used as the materials. Four P fertilization levels were at 0, 400, 800 and 1600 g per plant (P0, P4, P8 and P16 respectively). Fertilization was applied before floral primordia formation and after cone picked, respectively. The effects of P fertilizer on the female strobilus of P. massoniana clones and the changes of N, P contents in needles of different positions during floral primordia formation stage and early stage of flower bud differentiation were investigated. The results showed that compared with P0, the female strobilus of P8 and P16 were significantly increased by 67.4% and 61.2% in 2018 and 28.9% and 14.1% in 2019, respectively. There was a significant negative correlation between the female strobilus with the N content and N/P, a significant positive correlation between the female strobilus and the P content in needles. The responses of N and P contents in needles to P fertilization differed in clones with different fruiting abilities. In floral primordia formation stage, the N content of clones with weak fruiting ability was high, and the N/P was 11.5-12.5, while the P content of clones with strong fruiting abilities was high, and the N/P was 9.5-10.5. During this period, the P content of most clones under P8 treatment was the highest, while the N/P was lowest. In the early stage of flower bud differentiation, the N/P of two fruiting clones was 15.3-17.0 and 13.2-15.1, respectively. The P content in upside layer was significantly higher while N/P was significantly lower than that in middle and lower layers. In conclusion, the 800 g P fertilization per plant could increase the P content and reduce the N/P of needles during the floral primordia formation stage of clones with diffe-rent fruiting abilities, which was beneficial to the formation of female strobilus and promote the yield of clone seed orchards.

Protection from Endotoxin Shock by Selective Targeting of Proinflammatory Signaling to the Nucleus Mediated by Importin Alpha 5.

Endotoxin shock is induced by LPS, one of the most potent virulence factors of the Gram-negative bacteria that cause sepsis. It remains unknown if either proinflammatory stress-responsive transcription factors (SRTFs), ferried to nucleus by importin α5, or lipid-regulating sterol regulatory element binding proteins (SREBPs), transported to the nucleus by importin ß1, mediate endotoxin shock. A novel cell-penetrating peptide targeting importin α5 while sparing importin ß1 protected 80% of animals from death in response to a high dose of LPS. This peptide suppresses inflammatory mediators, liver glycogen depletion, endothelial injury, neutrophil trafficking, and apoptosis caused by LPS. In d-galactosamine-pretreated mice challenged by 700-times lower dose of LPS, rapid death through massive apoptosis and hemorrhagic necrosis of the liver was also averted by the importin α5-selective peptide. Thus, using a new tool for selective suppression of nuclear transport, we demonstrate that SRTFs, rather than SREBPs, mediate endotoxin shock.

Dual inhibition of endothelial miR-92a-3p and miR-489-3p reduces renal injury-associated atherosclerosis.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD) patients, however, the underlying mechanisms that link CKD and CVD are not fully understood and limited treatment options exist in this high-risk population. microRNAs (miRNA) are critical regulators of gene expression for many biological processes in atherosclerosis, including endothelial dysfunction and inflammation. We hypothesized that renal injury-induced endothelial miRNAs promote atherosclerosis. Here, we demonstrate that dual inhibition of endothelial miRNAs inhibits atherosclerosis in the setting of renal injury. METHODS: Aortic endothelial miRNAs were analyzed in apolipoprotein E-deficient (Apoe-/-) mice with renal damage (5/6 nephrectomy, 5/6Nx) by real-time PCR. Endothelial miR-92a-3p and miR-489-3p were inhibited by locked-nucleic acid (LNA) miRNA inhibitors complexed to HDL. RESULTS: Renal injury significantly increased endothelial miR-92a-3p levels in Apoe-/-;5/6Nx mice. Dual inhibition of miR-92a-3p and miR-489-3p in Apoe-/-;5/6Nx with a single injection of HDL + LNA inhibitors significantly reduced atherosclerotic lesion area by 28.6% compared to HDL + LNA scramble (LNA-Scr) controls. To examine the impact of dual LNA treatment on aortic endothelial gene expression, total RNA sequencing was completed, and multiple putative target genes and pathways were identified to be significantly altered, including the STAT3 immune response pathway. Among the differentially expressed genes, Tgfb2 and Fam220a were identified as putative targets of miR-489-3p and miR-92a-3p, respectively. Both Tgfb2 and Fam220a were significantly increased in aortic endothelium after miRNA inhibition in vivo compared to HDL + LNA-Scr controls. Furthermore, Tgfb2 and Fam220a were validated with gene reporter assays as direct targets of miR-489-3p and miR-92a-3p, respectively. In human coronary artery endothelial cells, over-expression and inhibition of miR-92a-3p decreased and increased FAM220A expression, respectively. Moreover, miR-92a-3p overexpression increased STAT3 phosphorylation, likely through direct regulation of FAM220A, a negative regulator of STAT3 phosphorylation. CONCLUSIONS: These results support endothelial miRNAs as therapeutic targets and dual miRNA inhibition as viable strategy to reduce CKD-associated atherosclerosis.

Lignocellulose degradation patterns, structural changes, and enzyme secretion by Inonotus obliquus on straw biomass under submerged fermentation.

This study examined the white rot fungus I. obliquus on the degradation of three types of straw biomass and the production of extracellular lignocellulolytic enzymes under submerged fermentation. The fungus process resulted in a highest lignin loss of 72%, 39%, and 47% in wheat straw, rice straw, and corn stover within 12days, respectively. In merely two days, the fungus selectively degraded wheat straw lignin by 37%, with only limited cellulose degradation (13%). Fourier transform infrared spectroscopy revealed that the fungus most effectively degraded the wheat straw lignin and rice straw crystalline cellulose. Scanning electronic microscopy showed the most pronounced structural changes in wheat straw. High activities of manganese peroxidase (159.0U/mL) and lignin peroxidase (123.4U/mL) were observed in wheat straw culture on Day 2 and 4, respectively. Rice straw was the best substrate to induce the production of cellulase and xylanase.

Low-protein diets affect ileal amino acid digestibility and gene expression of digestive enzymes in growing and finishing pigs.

The objective of this study was to evaluate effects of dietary crude protein (CP) intake on ileal amino acid digestibilities and expression of genes for digestive enzymes in growing and finishing pigs. In Experiment 1, 18 growing pigs (average initial BW = 36.5 kg) were assigned randomly into one of three treatments (n = 6/treatment group) representing normal (18 % CP), low (15 % CP), and very low (12 % CP) protein intake. In Experiment 2, 18 finishing pigs (average initial BW = 62.3 kg) were allotted randomly into one of three treatments (n = 6/treatment group), representing normal (16 % CP), low (13 % CP) and very low (10 % CP) protein intake. In both experiments, diets with low and very low CP were supplemented with crystalline amino acids to achieve equal content of standardized ileal digestible Lys, Met, Thr, and Trp, and were provided to pigs ad libitum. Daily feed intake, BW, and feed/gain ratios were determined. At the end of each experiment, all pigs were slaughtered to collect pancreas, small-intestine samples, and terminal ileal chymes. Samples were used for determining expression of genes for digestive enzymes and ileal amino acid digestibilities. Growing pigs fed the 12 % CP and 15 % CP diets had lower final body weight (P < 0.01) and ADG (P < 0.0001) when compared with pigs fed the 18 % dietary CP diet. Growing pigs fed with the 12 % CP diet showed higher digestibilities for CP (P < 0.05), DM (P < 0.05), Lys (P < 0.0001), Met (P < 0.01), Cys (P < 0.01), Thr (P < 0.01), Trp (P < 0.05), Val (P < 0.05), Phe (P < 0.05), Ala (P < 0.05), Cys (P < 0.01), and Gly (P < 0.05) than those fed the 18 % CP diet. Finishing pigs fed the 16 % CP diet had a higher (P < 0.01) final body weight than those fed the 10 % CP diet. mRNA levels for digestive enzymes (trypsinogen, chymotrypsin B, and dipeptidases-II and III) differed among the three groups of pigs (P < 0.05), and no difference was noted in the genes expression between control group and lower CP group. These results indicated that a reduction of dietary CP by a six-percentage value limited the growth performance of growing-finishing pigs and that a low-protein diet supplemented with deficient amino acids could reduce the excretion of nitrogen into the environment without affecting weight gain.

The Physiological Basis and Nutritional Function of Alpha-ketoglutarate.

Alpha-Ketoglutarate (AKG) is a biological substance that plays important roles in cell metabolism and physiology. AKG is synthesized from glucose or oxaloacetate plus pyruvate. As an intermediate of the tricarboxylic acid cycle, AKG is essential for the oxidation of fatty acids, amino acids, and glucose. Extracellular AKG is a significant source of energy for cells of the gastrointestinal tract. As a precursor for the synthesis of glutamate and glutamine in multiple tissues (including liver, skeletal muscle, heart, brain, and white adipose tissue), AKG bridges carbohydrate and nitrogen metabolism for both conservation of amino acids and ammonia detoxification. Additionally, emerging evidence shows that AKG is a regulator of gene expression and cell signaling pathways (including the mammalian target of rapamycin and AMPactivated protein kinase). Thus, AKG is an attractive dietary supplement in animal and human nutrition to improve cellular energy status, immunity, and health.