Balancing Redox Homeostasis to Improve l-Cysteine Production in Corynebacterium glutamicum.

l-Cysteine is a valuable sulfur-containing amino acid with applications across a wide range of fields. Recently, microbial fermentation has emerged as a method to produce l-cysteine. However, cellular redox stress from high levels of l-cysteine is a bottleneck for achieving efficient production. In this study, we aimed to facilitate l-cysteine biosynthesis by modulating cellular redox homeostasis through the introduction of the natural antioxidant astaxanthin in Corynebacterium glutamicum. To achieve this, we first introduced an exogenous astaxanthin synthesis module in C. glutamicum. Then, an l-cysteine-dependent autonomous bifunctional genetic switch was developed to dynamically regulate the l-cysteine and astaxanthin biosynthesis pathway to maintain cellular redox homeostasis. This regulation system achieved high biosynthesis of astaxanthin, which significantly facilitated l-cysteine production. Finally, engineered strain Cg-10 produced 8.45 g/L l-cysteine and 95 mg/L astaxanthin in a 5 L bioreactor, both of which are the highest reported levels in C. glutamicum.

Transcription factor OxyR regulates sulfane sulfur removal and L-cysteine biosynthesis in Corynebacterium glutamicum.

Sulfane sulfur, a collective term for hydrogen polysulfide and organic persulfide, often damages cells at high concentrations. Cells can regulate intracellular sulfane sulfur levels through specific mechanisms, but these mechanisms are unclear in Corynebacterium glutamicum. OxyR is a transcription factor capable of sensing oxidative stress and is also responsive to sulfane sulfur. In this study, we found that OxyR functioned directly in regulating sulfane sulfur in C. glutamicum. OxyR binds to the promoter of katA and nrdH and regulates its expression, as revealed via in vitro electrophoretic mobility shift assay analysis, real-time quantitative PCR, and reporting systems. Overexpression of katA and nrdH reduced intracellular sulfane sulfur levels by over 30% and 20% in C. glutamicum, respectively. RNA-sequencing analysis showed that the lack of OxyR downregulated the expression of sulfur assimilation pathway genes and/or sulfur transcription factors, which may reduce the rate of sulfur assimilation. In addition, OxyR also affected the biosynthesis of L-cysteine in C. glutamicum. OxyR overexpression strain Cg-2 accumulated 183 mg/L of L-cysteine, increased by approximately 30% compared with the control (142 mg/L). In summary, OxyR not only regulated sulfane sulfur levels by controlling the expression of katA and nrdH in C. glutamicum but also facilitated the sulfur assimilation and L-cysteine synthesis pathways, providing a potential target for constructing robust cell factories of sulfur-containing amino acids and their derivatives. IMPORTANCE C. glutamicum is an important industrial microorganism used to produce various amino acids. In the production of sulfur-containing amino acids, cells inevitably accumulate a large amount of sulfane sulfur. However, few studies have focused on sulfane sulfur removal in C. glutamicum. In this study, we not only revealed the regulatory mechanism of OxyR on intracellular sulfane sulfur removal but also explored the effects of OxyR on the sulfur assimilation and L-cysteine synthesis pathways in C. glutamicum. This is the first study on the removal of sulfane sulfur in C. glutamicum. These results contribute to the understanding of sulfur regulatory mechanisms and may aid in the future optimization of C. glutamicum for biosynthesis of sulfur-containing amino acids.

Sustainable production of astaxanthin in microorganisms: the past, present, and future.

Astaxanthin (3,3'-dihydroxy-4,4'-diketo-ß-carotene) is a type of C40 carotenoid with remarkable antioxidant characteristics, showing significant application prospects in many fields. Traditionally, the astaxanthin is mainly obtained from chemical synthesis and natural acquisition, with both approaches having many limitations and not capable of meeting the growing market demand. In order to cope with these challenges, novel techniques, e.g., the innovative cell engineering strategies, have been developed to increase the astaxanthin production. In this review, we first elaborated the biosynthetic pathway of astaxanthin, with the key enzymes and their functions discussed in the metabolic process. Then, we summarized the conventional, non-genetic strategies to promote the production of astaxanthin, including the methods of exogenous additives, mutagenesis, and adaptive evolution. Lastly, we reviewed comprehensively the latest studies on the synthesis of astaxanthin in various recombinant microorganisms based on the concept of microbial cell factory. Furthermore, we have proposed several novel technologies for improving the astaxanthin accumulation in several model species of microorganisms.

Design of a genetically encoded biosensor to establish a high-throughput screening platform for L-cysteine overproduction.

Metabolic engineering seeks to rewire the metabolic network of cells for the efficient production of value-added compounds from renewable substrates. However, it remains challenging to evaluate and identify strains with the desired phenotype from the vast rational or random mutagenesis library. One effective approach to resolve this bottleneck is to design an efficient high-throughput screening (HTS) method to rapidly detect and analyze target candidates. L-cysteine is an important sulfur-containing amino acid and has been widely used in agriculture, pharmaceuticals, cosmetics, and food additive industries. However, HTS methods that enable monitoring of L-cysteine levels and screening of the enzyme variants and strains to confer superior L-cysteine biosynthesis remain unavailable, greatly limiting the development of efficient microbial cell factories for L-cysteine production at the industrial scale. Here, we took advantage of the L-cysteine-responsive transcriptional regulator CcdR to develop a genetically encoded biosensor for engineering and screening the L-cysteine overproducer. The in vivo L-cysteine-responsive assays and in vitro electrophoretic mobility shift assay (EMSA) and DNase I footprint analysis indicated that CcdR is a transcriptional activator that specifically interacts with L-cysteine and binds to its regulatory region to induce the expression of target genes. To improve the response performance of the L-cysteine biosensor, multilevel optimization strategies were performed, including regulator engineering by semi-rational design and systematic optimization of the genetic elements by modulating the promoter and RBS combination. As a result, the dynamic range and sensitivity of the biosensor were significantly improved. Using this the excellent L-cysteine biosensor, a HTS platform was established by coupling with fluorescence-activated cell sorting (FACS) and was successfully applied to achieve direct evolution of the key enzyme in the L-cysteine biosynthetic pathway to increase its catalytic performance and to screen the high L-cysteine-producing strains from the random mutagenesis library. These results presented a paradigm of design and optimization of biosensors to dynamically detect metabolite concentrations and provided a promising tool enabling HTS and metabolic regulation to construct L-cysteine hyperproducing strains to satisfy industrial demand.

Engineering of Corynebacterium glutamicum for high-level γ-aminobutyric acid production from glycerol by dynamic metabolic control.

Synthetic biology seeks to reprogram microbial cells for efficient production of value-added compounds from low-cost renewable substrates. A great challenge of chemicals biosynthesis is the competition between cell metabolism and target product synthesis for limited cellular resource. Dynamic regulation provides an effective strategy for fine-tuning metabolic flux to maximize chemicals production. In this work, we created a tunable growth phase-dependent autonomous bifunctional genetic switch (GABS) by coupling growth phase responsive promoters and degrons to dynamically redirect the carbon flux for metabolic state switching from cell growth mode to production mode, and achieved high-level GABA production from low-value glycerol in Corynebacterium glutamicum. A ribosome binding sites (RBS)-library-based pathway optimization strategy was firstly developed to reconstruct and optimize the glycerol utilization pathway in C. glutamicum, and the resulting strain CgGly2 displayed excellent glycerol utilization ability. Then, the initial GABA-producing strain was constructed by deleting the GABA degradation pathway and introducing an exogenous GABA synthetic pathway, which led to 5.26 g/L of GABA production from glycerol. In order to resolve the conflicts of carbon flux between cell growth and GABA production, we used the GABS to reconstruct the GABA synthetic metabolic network, in which the competitive modules of GABA biosynthesis, including the tricarboxylic acid (TCA) cycle module and the arginine biosynthesis module, were dynamically down-regulated while the synthetic modules were dynamically up-regulated after sufficient biomass accumulation. Finally, the resulting strain G7-1 accumulated 45.6 g/L of GABA with a yield of 0.4 g/g glycerol, which was the highest titer of GABA ever reported from low-value glycerol. Therefore, these results provide a promising technology to dynamically balance the metabolic flux for the efficient production of other high value-added chemicals from a low-value substrate in C. glutamicum.

Effects of Methanol on Carotenoids as Well as Biomass and Fatty Acid Biosynthesis in Schizochytrium limacinum B4D1.

Schizochytrium is a promising source for the production of docosahexaenoic acid and astaxanthin. The effects of different methanol concentrations on astaxanthin, biomass, and production of the lipids, squalene, and total sterol in Schizochytrium limacinum B4D1 were investigated. Astaxanthin began to accumulate when the methanol concentration reached 3.2% and peaked at 5.6% methanol, with a 2,000-fold increase over that in the control. However, under cultivation with 5.6% methanol, the biomass, lipids, squalene, and total sterol decreased to various degrees. Transcriptomic analysis was performed to explore the effects of different methanol concentrations (0%, 3.2%, and 5.6%) on the expression profile of B4D1. Three key signaling pathways were found to play important roles in regulating cell growth and metabolism under cultivation with methanol. Five central carbon metabolism-associated genes were significantly downregulated in response to 5.6% methanol and thus were expected to result in less ATP and NADPH being available for cell growth and synthesis. High methanol conditions significantly downregulated three genes involved in fatty acid and squalene/sterol precursor biosynthesis but significantly upregulated geranylgeranyl diphosphate synthase, lycopene ß-cyclase, and ß-carotene 3-hydroxylase, which are involved in astaxanthin synthesis, thus resulting in an increase in the levels of precursors and the final production of astaxanthin. Additionally, the transcriptional levels of three stress response genes were upregulated. This study investigates gene expression profiles in the astaxanthin producer Schizochytrium when grown under various methanol concentrations. These results broaden current knowledge regarding genetic expression and provide important information for promoting astaxanthin biosynthesis in SchizochytriumIMPORTANCESchizochytrium strains are usually studied as oil-producing strains, but they can also synthesize other secondary metabolites, such as astaxanthin. In this study, methanol was used as an inducer, and we explored its effects on the production of astaxanthin, a highly valuable substance in Schizochytrium Methanol induced Schizochytrium to synthesize large amounts of astaxanthin. Transcriptomic analysis was used to investigate the regulation of signaling and metabolic pathways (mainly relative gene expression) in Schizochytrium grown in the presence of various concentrations of methanol. These results contribute to the understanding of the underlying molecular mechanisms and may aid in the future optimization of Schizochytrium for astaxanthin biosynthesis.

The effects of abscisic acid, salicylic acid and jasmonic acid on lipid accumulation in two freshwater Chlorella strains.

Sustainable renewable energy is being hotly debated globally because the continued use of finite fossil fuels is now widely recognized as being unsustainable. Microalgae potentially offer great opportunities for resolving this challenge. Abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) are involved in regulating many physiological properties and have been widely used in higher plants. To test if phytohormones have an impact on accumulating lipid for microalgae, ABA, JA and SA were used to induce two Chlorella strains in the present study. The results showed 1.0 mg/L ABA, 10 mg/L SA, and 0.5 mg/L JA, led strain C. vulgaris ZF strain to produce a 45%, 42% and 49% lipid content that was 1.8-, 1.7- and 2.0-fold that of controls, respectively. For FACHB 31 (number 31 of the Freshwater Algae Culture Collection at the Institute of Hydrobiology, Chinese Academy of Sciences), the addition of 1.0 mg/L ABA, 10 mg/L SA, and 0.5 mg/L, JA produced 33%, 30% and 38% lipid content, which was 1.8-, 1.6- and 2.1-fold that of controls, respectively. As for lipid productivity, 1.0 mg/L ABA increased the lipid productivity of C. vulgaris ZF strain and FACHB-31 by 123% and 44%; 10 mg/L SA enhanced lipid productivity by 100% and 33%; the best elicitor, 0.5 mg/L JA, augmented lipid productivity by 127% and 75% compared to that of controls, respectively. The results above suggest that the three phytohormones at physiological concentrations play crucial roles in inducing lipid accumulation in Chlorella.

Effects of protease-treated royal jelly on muscle strength in elderly nursing home residents: A randomized, double-blind, placebo-controlled, dose-response study.

Although we have found that protease-treated royal jelly (pRJ) benefit for the skeletal muscle mass and strength in the aged animals, the potential beneficial effects have not been evaluated in humans. The aim of this study was to determine whether pRJ intake had beneficial effects on muscle strength in elderly nursing home residents. One hundred and ninety-four subjects enrolled into this multicenter, randomized, double-blind, placebo-controlled study. Subjects received either placebo(Group 1), pRJ 1.2 g/d(Group 2), or 4.8 g/d(Group 3). Data through 1 year are reported for 163 subjects. The primary outcome measure is handgrip strength. Secondary outcomes include several physical performance tests (six-minute walk test, timed up and go test, and standing on one leg with eyes closed). The dropout rate was 16.0%. The means (95% confidence interval) of change in handgrip strength for placebo, low-dose, and high-dose groups are -0.98(-2.04,0.08), 0.50(-0.65,1.65) and 1.03(-0.37,2.44) kg (P = 0.06, P for trend = 0.02), respectively. No significant effects of the interventions were observed for physical performances. These findings suggest that pRJ treatment might not improve, but rather attenuate the progression of decrease in muscle strength in elderly people. In addition, we have not found that pRJ intervention can achieve improvement or attenuating the decrease in physical performance.

Elevated serum complement C3 levels are associated with prehypertension in an adult population.

Prehypertension is a public health epidemic associated with various adverse outcomes, but can be reversed by timely intervention. However, little attention has been paid to prehypertension. Complement C3 is a central hub of complement-related immune system. We examined the association between C3 and prehypertension in an adult population for the first time, aiming to investigate whether pro-inflammatory immune response is involved in the prehypertensive state. About 7820 Tianjin residents without hypertension were categorized into sex-specific quintiles based on their serum concentration of complement C3. Adjusted logistic regression models were used separately by gender to assess the association between C3 quintiles and the prevalence of prehypertension. After multiple adjustment, the odds ratios (95% confidence interval) for prehypertension across increasing quintiles of C3 were 1.00 (reference), 1.02 (0.84, 1.25), 1.15 (0.94, 1.42), 1.25 (1.01, 1.54), and 1.71 (1.35, 2.17) (p for trend < 0.0001) among men and were 1.00 (reference), 1.17 (0.92, 1.49), 1.13 (0.88, 1.44), 1.15 (0.89, 1.48), and 1.40 (1.07, 1.84) (p for trend = 0.03) among women. The findings suggested that elevated serum C3 levels are associated with prehypertension. Reducing inflammation may be a potential therapeutic strategy for prehypertension and hypertension that is worthy of further studies and discussion.

Dietary patterns are associated with depressive symptoms among Chinese adults: a case-control study with propensity score matching.

PURPOSE: Previous studies have indicated that consumption of particular foods or nutrients is associated with depressive symptoms, but little is known about the role of overall dietary patterns in depressive symptoms. We design this case-control study to evaluate the associations between dietary patterns and high depression symptoms in Chinese adults. METHODS: A total of 1351 participants with high depressive symptoms were matched with 1351 controls using the 1:1 ratio propensity score matching method. Dietary intake was assessed using a valid self-administered food frequency questionnaire, and high depressive symptoms were assessed with the Zung Self-Rating Depression Scale, wherein cutoff point of 45 was used as a definition of high depressive symptoms. RESULTS: Exploratory factor analysis revealed three dietary patterns (vegetables and fruits pattern; sweets pattern; and animal foods pattern) explaining 25.1 % of the total variance. Compared with the participants in the lowest quartile, the participants in the highest quartile of vegetables and fruits pattern, which was defined as a healthy pattern, were associated with reduced odds of high depressive symptoms (OR 0.65, 95 % CI 0.52-0.83, P for trend <0.001) while the sweets pattern (OR 1.33, 95 % CI 1.06-1.66) and the animal foods pattern (OR 1.79, 95 % CI 1.43-2.24, P for trend <0.0001) were associated with increased prevalence of high depressive symptoms, respectively. CONCLUSION: The present study adds to the evidence that the sweets pattern and animal foods pattern are positively associated with the prevalence of high depressive symptoms. In contrast, the dietary pattern rich in vegetables, fruits, and soya bean products, but low in animal foods, candied fruits, cakes, ice cream, sugared beverages, and alcoholic drinks is negatively associated with the prevalence of high depressive symptoms.

Both muscle mass and muscle strength are inversely associated with depressive symptoms in an elderly Chinese population.

OBJECTIVE: Few population studies have examined the association between skeletal muscle and depressive symptoms. The aim of this study was to examine whether low muscle mass and muscle strength were associated with the depressive symptoms in elderly Chinese. METHODS: A cross-sectional study was conducted with 1046 elderly in Tianjin, China. Depressive symptoms were examined using the 30-item Geriatric Depression Scale. A Geriatric Depression Scale score of ≥11 was used to indicate depressive symptoms. Skeletal muscle mass was indicated using a skeletal muscle mass index (SMI) that was measured by bioimpedance analysis and muscle strength was measured by dynamometer. RESULTS: In a multiple logistic regression analysis, subjects in the lowest quartile of SMI or muscle strength had a significantly higher risk for depressive symptoms compared with those in the fourth quartile. The odds ratios and 95% confidence interval for depressive symptoms risk in the lowest quartile of SMI compared with the highest after adjusting for potential confounding factors were 10.1 (2.25, 58.3) in men and 3.17 (1.07, 9.95) in women. The odds ratios (95% confidence interval) for depressive symptoms risk in the lowest quartile of muscle strength compared with the highest after adjusting for potential confounding factors were 2.55 (1.02, 6.67) in men and 4.18 (1.83, 10.2) in women. CONCLUSIONS: Both muscle mass and muscle strength are inversely associated with depressive symptoms in elderly Chinese. These findings may provide novel insights linking skeletal muscle and depressive symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

The Relationship Between Thyroid Function and the Prevalence of Type 2 Diabetes Mellitus in Euthyroid Subjects.

Purpose: Thyroid hormones (THs) are primarily responsible for the regulation of energy balance and metabolism, suggesting that TH levels may contribute to the development of type 2 diabetes mellitus (T2DM). However, few studies have investigated the relationship between TH and T2DM in a general population. The aim of this study was to evaluate whether serum TH levels within the reference range are related to T2DM. Methods: A cross-sectional study (n = 15,296) was performed in Tianjin, China. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay, and T2DM was defined according to the American Diabetes Association criteria. Multiple logistic regression models were used to assess the sex-specific relationships between FT3, FT4, FT3/FT4 ratios, and TSH quintiles and T2DM. Results: The prevalence of T2DM was 16.2% in males and 7.7% in females. In males, the multivariable-adjusted odds ratios (95% confidence interval) of T2DM for increasing quintiles of FT3, FT4, and FT3/FT4 ratios were 1.00, 0.75(0.63 to 0.89), 0.70(0.58 to 0.84), 0.63(0.52 to 0.76), 0.56(0.46 to 0.68; P for trend < 0.0001); 1.00, 1.05(0.87 to 1.27), 1.16(0.96 to 1.40), 1.09(0.90 to 1.31), 1.29(1.07 to 1.56; P for trend = 0.01); and 1.00, 0.69(0.58 to 0.83), 0.72(0.60 to 0.86), 0.59(0.48 to 0.71), and 0.55(0.46 to 0.66; P for trend < 0.0001), respectively. Similar results also were observed in females. In contrast, a strong negative correlation between TSH and T2DM was observed in males, but not in females. Conclusions: This study demonstrated that decreased FT3, FT3/FT4 ratios, and increased FT4 levels are independently related to a higher prevalence of T2DM in both males and females, and TSH is inversely related to T2DM in males only.

Association between dietary patterns and metabolic syndrome in Chinese adults: a propensity score-matched case-control study.

Previous studies indicated that dietary patterns were associated with metabolic syndrome (MS), but little is known in Chinese. We design this case-control study to evaluate the associations between dietary patterns and MS in Chinese adults. In this study, 1492 participants with MS were matched with 1492 controls using the 1:1 ratio propensity score matching methods. Dietary intake was assessed using a valid self-administered food frequency questionnaire, and MS was defined in accordance with the criteria of the American Heart Association scientific statement of 2009. Higher scores for the high-protein/cholesterol pattern were associated with higher prevalence of MS. Compared with the participants in the lowest quartile, the odds ratio (OR) for the extreme quartile was 1.36 (95% confidence interval (CI), 1.10-1.68) and the P for trend <0.01 after adjusted for the other two dietary pattern scores. We also found a moderate consumption of the balanced pattern was associated with the lowest prevalence of MS. The ORs across quartiles of the balanced pattern were 1 (reference), 0.83 (95% CI, 0.68-1.02), 0.69 (95% CI, 0.56-0.85), and 0.84 (95% CI, 0.68-1.04) after adjustment. Our study demonstrates that there is a strong association between a diet rich in animal offal, animal blood, meat, and sausage and a higher prevalence of MS.

The overall computer/mobile devices usage time is related to newly diagnosed non-alcoholic fatty liver disease: a population-based study.

BACKGROUND: The computer/mobile devices usage time (CMD-UT) is closely related to a sedentary lifestyle, which is an important risk factor for non-alcoholic fatty liver disease (NAFLD). But their direct relationship remains unclear. AIMS: We aimed to examine the relationship between CMD-UT and newly diagnosed non-alcoholic fatty liver disease (NAFLD) in Chinese adults. METHODS: This cross-sectional study was conducted on 7516 adults in Tianjin, China. The CMD-UT was collected via a questionnaire included five categories. NAFLD [with normal or elevated alanine transaminase (ALT) levels] was diagnosed by at least twice liver ultrasonography examinations and serum ALT concentrations (>41 U/L in males and >33 U/L in females). RESULTS: The prevalence of overall NAFLD, NAFLD with normal or elevated ALT levels was 18.2, 14.2, and 4.0%, respectively. After adjustments for potential confounding factors, the odds ratios (95% confidence interval) of having overall NAFLD by increasing CMD-UT levels were 1.00 for <1 h/d, 1.58 (1.22-2.05) for 1-3 h/d, 1.58 (1.18-2.11) for 3-5 h/d, 1.65 (1.21-2.27) for 5-10 h/d, and 1.99 (1.29-3.05) for ≥10h/d (P-trend for CMD-UT levels = 0.02), respectively. Similar relations were observed with the use of NAFLD with normal or elevated ALT levels. CONCLUSIONS: The present study is the first to find that CMD-UT levels are independently associated with NAFLD. Key Messages The computer/mobile devices usage time levels are independently associated with the prevalence of non-alcoholic fatty liver disease.

Relationship between grip strength and newly diagnosed nonalcoholic fatty liver disease in a large-scale adult population.

Enhanced muscle strength is often related to improved insulin sensitivity and secretion, control of lipid metabolism, and increased secretion of myokines. These factors have emerged as important mechanisms involved in the development and progression of nonalcoholic fatty liver disease (NAFLD), implying that muscle strength may be a useful predictor for NAFLD. We aimed to assess the relationship between grip strength (GS) and NAFLD in a large-scale adult population. GS was assessed using an electronic hand-grip dynamometer, and NAFLD was diagnosed by the liver ultrasonography. Multiple logistic regression analysis was used to assess the relationship between the quartiles of GS per body weight and the prevalence of NAFLD. After adjusting for potentially confounding factors, the odds ratios (95% confidence interval) for overall NAFLD, NAFLD with normal alanine aminotransferase levels, and NAFLD with elevated alanine aminotransferase levels across the quartiles of GS were 1.00 (reference), 0.89 (0.78, 1.01), 0.77 (0.67, 0.89), and 0.67 (0.57, 0.79); 1.00 (reference), 0.91 (0.80, 1.04), 0.79 (0.68, 0.92), and 0.72 (0.61, 0.85); 1.00 (reference), 0.77 (0.61, 0.98), 0.67 (0.51, 0.86), and 0.53 (0.40, 0.71) (all P for trend < 0.01), respectively. This is the first study shows that increased GS is independently associated with lower prevalence of NAFLD.

Association between Serum Ferritin Concentrations and Depressive Symptoms among Chinese Adults: A Population Study from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIHealth) Cohort Study.

Depressive symptoms have become the most important global public health issue. Iron plays an important role in brain function, cognition, and behavior, and its impacts on depressive symptoms may be multifactorial with both positive and negative effects. Previous observational studies focusing on the association between iron status and depressive symptoms showed inconsistent results. Ferritin is a ubiquitous intracellular protein that can store and release iron and is widely used as a clinical biomarker to evaluate iron status. We performed a cross-sectional study to examine the relationship between serum ferritin and depressive symptoms among 3,839 subjects who were from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort. Depressive symptoms were assessed using the Chinese version of 20-item self-rating Depression Scale (SDS) with 4 cutoffs (40, 45, 48 and 50) to indicate elevated depressive symptoms (40 was the primary cut-off). The prevalence of depressive symptoms was 36.5%, 17.6%, 11.0% and 7.0% for SDS ≥40, ≥45, ≥48 and ≥50, respectively. With the primary cut-off point of 40, multiple potential confounding factors were adjusted and the odds ratios (95% confidence interval) of having elevated depressive symptoms by quartiles of serum ferritin concentrations were 1.00 (reference), 1.10 (0.91, 1.34), 0.81 (0.66, 1.01) and 1.02 (0.81, 1.28) for the first, second, third and fourth quartile, respectively (P for trend = 0.76). Similar relations were observed with the use of other cut-offs as a definition of depressive symptoms. In conclusion, there is no significant relationship between serum ferritin concentrations and depressive symptoms among Chinese adults.

Serum levels of immunoglobulins in an adult population and their relationship with type 2 diabetes.

OBJECTIVE: Some studies have found patients with diabetes had an impaired humoral immune response. Immunoglobulins provide key information on the humoral immune status. But few population-based studies comprehensively estimated the serum immunoglobulins concentration in type 2 diabetes (T2D). So we design a cross-sectional study to investigate the relationships between immunoglobulin levels and prevalence of T2D in a large-scale adult population. METHODS: A cross-sectional assessment was performed in 10,691 participants living in Tianjin, China. Type 2 diabetes was defined in accordance with the criteria of the world health organization, and serum levels of immunoglobulins were determined by the immunonephelometric technique. Adjusted logistic models were used to assess relationships between the quintiles of immunoglobulins concentration and the prevalence of T2D. RESULTS: In this study, the prevalence of T2D was 11.7%, and the means (standard deviation) of immunoglobulins (IgG, IgE, IgM, IgA) were 1192.3 (241.1)mg/dL, 92.3 (234.6)IU/mL, 104.8 (55.8)mg/dL, 234.1 (96.2)mg/dL, respectively. The adjusted odds ratio (95% confidence interval) of T2D for the highest immunoglobulins (IgG, IgE, IgM, IgA) quintile, when compared to the lowest quintile were 0.64 (0.52, 0.78), 1.00 (0.81, 1.22), 0.77 (0.62, 0.95) and 1.57 (1.29, 1.92), respectively. CONCLUSIONS: Decreased IgG and IgM, and increased IgA levels were independently related to the prevalence of T2D among the adult population. Our findings indicate that the immunoglobulins might useful predictive factors for T2D in the general adult population. Further studies are needed to explore the causality and exact mechanisms of immunoglobulins in T2D.

The predictive value of mean serum uric acid levels for developing prediabetes.

AIMS: We aimed to assess the predictive value of mean serum uric acid (SUA) levels for incident prediabetes. METHODS: Normoglycemic adults (n=39,353) were followed for a median of 3.0years. Prediabetes is defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired HbA1c (IA1c), based on the American Diabetes Association criteria. Serum SUA levels were measured annually. Four diagnostic strategies were used to detect prediabetes in four separate analyses (Analysis 1: IFG. Analysis 2: IFG+IGT. Analysis 3: IFG+IA1c. Analysis 4: IFG+IGT+IA1c). Cox proportional hazards regression models were used to assess the relationship between SUA quintiles and prediabetes. C-statistic was additionally used in the final analysis to assess the accuracy of predictions based upon baseline SUA and mean SUA, respectively. RESULTS: After adjustment for potential confounders, the hazard ratios (95% confidence interval) of prediabetes for the highest versus lowest quintile of mean SUA were 1.22 (1.10, 1.36) in analysis 1; 1.59 (1.23, 2.05) in analysis 2; 1.62 (1.34, 1.95) in analysis 3 and 1.67 (1.31, 2.13) in analysis 4. In contrast, for baseline SUA, significance was only reached in analyses 3 and 4. Moreover, compared with baseline SUA, mean SUA value was associated with a significant increase in the C-statistic (P<0.001). CONCLUSIONS: Mean SUA value was strongly and positively related to prediabetes risk, and showed better predictive ability for prediabetes than baseline SUA.

NUT CONSUMPTION IS ASSOCIATED WITH DEPRESSIVE SYMPTOMS AMONG CHINESE ADULTS.

BACKGROUND: Affective disorders, especially depressive symptoms, bring such a burden to mortality and morbidity that they are associated with physical and psychological health and quality of life. Nuts, a foodstuff rich in multiple micronutrients, macronutrients, and other useful components, were considered to be a protector against depressive symptoms. Here, we conducted an analysis to examine the relationship between nut consumption and depressive symptoms. METHODS: The study performed a cross-sectional study to examine whether nut consumption is related to depressive symptoms among 13,626 inhabitants in Tianjin. Nut consumption was assessed using a validated food frequency questionnaire and depressive symptoms was assessed using the Chinese version of 20-item Self-rating Depression Scale (SDS) with four cutoffs (40, 45, 48, and 50) to indicate elevated depressive symptoms. RESULTS: The prevalence of depressive symptoms was 38.7, 19.1, 11.4, and 7.3% for SDS ≥40, 45, 48, and 50, respectively. After adjustments for potential confounding factors, the odds ratios (95% confidence interval) of having elevated depressive symptoms with SDS ≥40 by increasing frequency of nut consumption were 1.00 for

Relationship of anabolic and catabolic biomarkers with muscle strength and physical performance in older adults: a population-based cross-sectional study.

BACKGROUND: Previous studies have found inflammation, growth factors, and androgen signaling pathways all contribute to sarcopenia. However, few studies simultaneously have investigated the association between these potential risk factors and sarcopenia among older people. The aim of the study was to investigate whether elevated levels of inflammatory cytokines combined with low levels of anabolic hormone have a synergy effect on muscle strength and functional decline in older people. METHODS: We designed a cross-sectional study of 1,131 subjects aged 60 years and older. Concentrations of serum C-reactive protein, insulin-like growth factor 1 and dehydroepiandrosteronesulphate were assessed using chemiluminescent immunoassays. Handgrip strength was measured using a dynamometer, and physical performance was assessed using a four-meter gait speed and Timed Up and Go test. We defined poor physical performance as a 4-m gait speed <0.8 m/s or Timed Up and Go test ≥13.5 s. RESULTS: After adjustment for potential confounding factors, in multiple linear regression analysis, C-reactive protein levels are inversely related to handgrip strength (P <0.01), and in multiple logistic regression analysis, C-reactive protein levels are inversely related to poor physical performance (P for trend <0.05) in males, but not in females. After combining three biomarkers, no significant results were observed between biomarker scores and muscle strength or physical performance. CONCLUSIONS: In older males, higher serum C-reactive protein levels, but not insulin-like growth factor 1 and dehydroepiandrosteronesulphate levels, are independently related to lower muscle strength and poor physical performance. In this study we did not observe that a combination of higher catabolic biomarkers and lower anabolic biomarkers were better predictors for muscle strength and physical performance.