Background:Diabetic kidney disease (DKD) is a multifactorial complication of diabetes involving mitochondrial dysfunction and immune cell infiltration. However, the causal relationships remain unclear. Methods:We applied Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to investigate the roles of mitochondrial gene expression and immune cells in DKD. Additionally, peripheral blood mononuclear cells (PBMCs) from DKD patients were analyzed for differential gene expression. Results:Higher expression of mitochondrial genes PCCB, ACADM, ADHFE1, OCIAD1, and FIS1 increased DKD risk, while genes like NT5DC2, ATP5MC3, and GLYCTK decreased risk. Immune traits, including human leukocyte antigen (HLA)-DR + plasmacytoid dendritic cells (pDCs), mediated the effects of mitochondrial dysfunction on DKD. scRNA-seq revealed significant downregulation of ATP5MC3, GLYCTK, and NT5DC2 in podocytes (PODOs) and tubular cells in DKD kidneys, alongside increased infiltration of helper T cells, B cells, dendritic cells (DCs), and plasma cells. PBMC analysis highlighted the upregulation of proinflammatory genes (CXCL2, CXCL3, and others) in DKD patients. Conclusion:This study highlights the complex interplay between mitochondrial dysfunction and immune cell infiltration in DKD pathogenesis. Key mitochondrial genes and immune traits identified here offer novel therapeutic targets such as ATP5MC3, GLYCTK, and DC pathways.

Conjugated linoleic acid (CLA) may prevent the development of obesity and metabolic disorders. However, the effects of CLA on inflammation and glucose metabolism are controversial. The underlying mechanisms governing the gut microbiota and sexual dimorphisms have also not been elucidated. The present study assessed the effect of CLA on glucose and lipid metabolism in established obesity and examined the mechanism of action based on gut microbiota. Four-week-old C57BL/6J mice were fed a high-fat diet (HFD) for 10 weeks to induce obesity. The diet-induced obese (DIO) mice were fed an HFD supplemented with mixed CLA (50% cis-9, trans-11 isomer and 50% trans-10, cis-12 isomers, 0.2% wt/wt) for 15 weeks. CLA supplementation remarkably reversed body weight in both sexes. CLA favored anti-inflammatory microbiota in male mice, mediating increased short-chain fatty acids and decreased lipopolysaccharide (LPS) production, which alleviated global inflammation and improved insulin sensitivity via inhibition of the TLR4-NF-kappa B pathway in adipose tissue. CLA promoted the growth of hydrogen sulfide-producing Desulfovibrio and the release of LPS in female mice, which aggravated adipose inflammation and insulin resistance. Although CLA impaired glucose metabolism in females, brown adipose tissue was significantly activated with browning of white adipose tissue in both sexes, which led to enhanced energy expenditure. Fecal transplantation from CLA-treated mice to DIO mice mimicked the sex-dependent phenotype. In conclusion, CLA decreased body weight and increased energy expenditure but sex-dependently modulated insulin resistance via the gut-adipose axis.

AbstractThe relationship between SFA consumption and the risk of overweight/obesity remains unclear. Epidemiological evidence is lacking among Chinese population. This study aimed to investigate the association between individual dietary SFA intake and the risk of overweight/obesity in Chinese adults. Data from 8465 adults with BMI < 24 kg/m2 at entry in the China Health and Nutrition Survey (1989–2011) were analysed. Three-day 24-h dietary records were used to collect dietary data. Cox proportional hazards regression models were constructed to estimate hazard ratios (HR) and 95 % CI for the risk of developing overweight or obesity. A total of 3171 incident cases of overweight/obesity were identified (1649 for women and 1522 for men) during a median of 11 years of follow-up. Compared with the lowest category, the intake of total SFA (TSFA) showed no significant association with the risk of overweight/obesity. However, an increased risk of overweight/obesity was observed with a higher intake of medium chain SFA (MCSFA) (Ptrend = 0·004), especially decanoic acid (10:0) (HR was 1·25 (95 % CI 1·10, 1·42) comparing the highest category with the reference group; Ptrend < 0·001), whereas an inverse relationship was observed for hexanoic acid (6:0) consumption; compared with non-consumers, 6:0 intake was associated with 32 % lower risk of overweight/obesity (HR: 0·68 (95 % CI 0·56, 0·84); Ptrend < 0·001). Overall, the intake of subtypes of MCSFA but not TSFA was associated with the risk of overweight/obesity. Increasing hexanoic acid (6:0) and limiting decanoic acid (10:0) consumption may be protective for overweight/obesity among Chinese population.

BACKGROUNDEvidence suggests that the relations between intakes of individual fatty acids and risk of type 2 diabetes (T2D) vary. However, associations between intakes of different cooking oils as sources of fatty acids and incident T2D remain largely unknown.OBJECTIVESWe aimed to evaluate relations between intakes of individual cooking oils and incident T2D in a nationwide Chinese cohort.METHODSOverall 15,022 Chinese adults aged ≥20 y from the China Health and Nutrition Survey (CHNS) without self-reported T2D at entry in the 1997, 2000, 2004, 2006, or 2009 rounds were followed up until 2011. Consumption of various cooking oils/fats including lard, peanut oil, soybean oil, canola oil, sesame oil, and refined blended plant oil was assessed using 3-d 24-h records in each survey and the cumulative mean intake was calculated. Multivariable-adjusted Cox proportional hazards regression models were constructed to estimate the HRs of T2D.RESULTSA total of 1014 cases were recorded after a median follow-up of 14 y. The intakes of animal and plant cooking oils/fats were both associated with higher T2D risk. Compared with nonconsumers, multivariable-adjusted HRs and 95% CIs for the highest tertiles were 1.31 (1.03, 1.67) for lard, 1.36 (1.10, 1.66) for peanut oil, 1.14 (0.91, 1.43) for soybean oil, 1.11 (0.87, 1.43) for canola oil, 1.02 (0.79, 1.32) for sesame oil, and 1.42 (1.12, 1.82) for refined blended plant oil. Substituting 1 tablespoon/d (8 g · 2000 kcal-1 · d-1) of soybean oil for the sum of lard, peanut oil, refined blended plant oil, and other plant oils was associated with a 3% (HR: 0.97; 95% CI: 0.95, 0.99) lower risk of T2D.CONCLUSIONSIntakes of lard, peanut oil, and refined blended plant oil but not soybean oil, canola oil, and sesame oil are associated with higher T2D risk. Reducing the consumption of cooking oils in general may be protective against T2D among the Chinese population.This trial was registered at clinicaltrials.gov as NCT03259321.

Background:Dietary intakes of total and specific types of saturated fatty acids (SFAs) in relation to total mortality remain largely unknown in China. Objective:We assessed the associations of total and individual SFA intakes with total mortality in a Chinese nationwide population. Methods:This prospective analysis included 7888 women and 6495 men, aged >20 y, from the China Health and Nutrition Survey (1989-2011). Cumulative mean of SFA intake was calculated based on 3 d of 24-h records in each round of the survey. Multivariable Cox proportional hazard models were used to estimate HR and 95% CI. Results:There were 1011 deaths during a median of 14 y of follow-up. In isocaloric nutrient density models that replace total carbohydrates, intakes of total SFAs and even-chain SFAs were associated with higher total mortality in women but not in men. Compared with the lowest quartiles, the HRs (95% CIs) in the highest quartiles were 1.65 (1.03, 2.62) for total SFAs (P-trend = 0.042) and 1.83 (1.13, 2.94) for even-chain SFAs (P-trend = 0.016) in women. Intake of odd-chain SFAs was associated with lower total mortality both in men [HR (95% CI): 0.64 (0.47, 0.87); P-trend = 0.01] and in women [HR (95% CI): 0.59 (0.42, 0.84); P-trend = 0.0013]. Moreover, intake of medium-chain SFAs was linked with lower total mortality in men [HR (95% CI): 0.64 (0.44, 0.93); P-trend = 0.013]. However, isocalorically replacing 1% of energy from unsaturated fatty acids with even-chain SFAs was associated with higher total mortality in men [HRs (95% CIs): 1.08 (0.97, 1.20) and 1.39 (1.20, 1.60) for replacing PUFAs and MUFAs, respectively]. Conclusions:Total SFA and even-chain SFA intake was associated with higher total mortality in women, whereas intake of odd-chain SFAs was related to lower total mortality in both sexes. This analysis of cohort was registered at clinicaltrials.gov as NCT03281512.

Whether fish and marine omega-3 polyunsaturated fatty acid (PUFA) intakes are linked to type 2 diabetes (T2D) risk remains unclear in China. We aimed to assess the long-term associations in a nationwide cohort. Overall 15,100 Chinese adults, aged ≥20 years, were included from China Health and Nutrition Survey. The cumulative averages of fish and marine omega-3 PUFA intakes were evaluated based on 3-day 24-h records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of T2D risk. Overall 1017 T2D cases were documented over a median of 14 years of follow-up. Compared with non-fish consumers, low and moderate fish consumption were associated with higher T2D risk whereas high fish consumption was not associated. Multivariable-adjusted HRs (95% CIs) for low and moderate fish consumption were 1.43 (1.09, 1.86) and 1.42 (1.07, 1.85) respectively in men, and were 1.58 (1.22, 2.02) and 1.39 (1.08, 1.83) respectively in women. In meat substitution analyses, low and moderate fish consumption was related to 55% and 69% higher T2D risk for men, and was associated with 68% and 54% higher T2D risk for women, respectively. Fried but not non-fried fish intake was associated with higher T2D risk. Intake of marine omega-3 PUFAs was dose-dependently associated with higher T2D risk for both men and women (P-trend<0.001). Overall low and moderate intakes of fish, especially fried fish, and marine omega-3 PUFAs were associated with higher T2D risk. Current level of fish and marine omega-3 PUFA consumption is not protective against T2D incidence among Chinese people.

SCOPE To assess the associations of plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with body fat in a population-based sample and explore the mechanism of action based on browning of white adipose tissue (WAT) in high-fat-diet-induced obese (DIO) mice and 3T3-L1 adipocytes. METHODS AND RESULTS Plasma EPA and DHA of 1719 adults in the National Health and Nutrition Examination Survey (2003-2004) are determined by gas chromatography mass spectrometry, while total body fat is measured by dual-energy X-ray absorptiometry. DIO mice are fed a high-fat diet supplemented with EPA or DHA (1% wt/wt) for 15 weeks and 3T3-L1 preadipocytes are treated with EPA or DHA during differentiation. Plasma DHA but not EPA is associated with lower body fat mass (ptrend < 0.0001), which persists in overweight/obese subjects (ptrend = 0.02). DHA supplementation reduces inguinal WAT and exhibits a more pronounced thermogenic effect than EPA in DIO mice. In vitro, the browning process is induced after 2-day and 6-day treatment with DHA and EPA, respectively. CONCLUSION Plasma DHA but not EPA is inversely associated with body fat mass. The more potent anti-adipogenic effect of DHA than EPA may involve a better capability of inducing browning of WAT for DHA.

In China, polyacrylamide used for municipal water supply and oil exploitation can be degraded to acrylamide which is harmful to human body under natural conditions. Swedish National Food Administration also found high content of acrylamide in fried and baked starchy foods in 2002. At present, most studies focus on the neurotoxicity and carcinogenicity of acrylamide. There is limited research on its developmental toxicity. This article introduces the basic properties and metabolism of acrylamide, and summarizes the food rich in acrylamide. This review focuses on the embryonic, nervous system, cardiac and reproductive organ developmental toxicity of acrylamide.

Sea cucumber chondroitin sulfate (CHS) is one of the important bioactive substancesins in sea cucumber body wall. Since its multiple bioactive functions have been validated, CHS is considered as a potential ingredient of novel functional foods. Similar to most carbohydrates, CHS lacks specific chromophores and fluorescence groups. Based on this background, the aim of this study was to construct fluorescence labelling of CHS. The polysaccharide was derivatized by hydrogen bromide activation method with 6-amino-fluorescein as the fluorescent dye. As a result, each molecule of the labelled product approximately contained 4.4 molecules of 6-amino-fluorescein. The optimal fluorescence excitation and emission wavelengths of the labelled CHS were 495 and 520 nm, respectively. Additionally, its molecular weight and sulfate content were determined. Infrared spectroscopy showed that the structural characteristics of the polysaccharide did not significantly change after labeling. The labelled CHS exhibited strong fluorescence intensity and stability in neutral and alkaline environments. The influence of NaCl in the solution environment on the labelled CHS was limited. The establishment of this fluorescence labeling method will facilitate further research on the absorption and metabolism, functions and underlying mechanisms of CHS and its interactions with other biomolecules.

Unraveling the role of dietary lipids is beneficial to treat obesity and metabolic dysfunction. Nonetheless, how dietary lipids affect existing obesity remains unknown. Arachidonic acid (AA), a derivative of linoleic acid, is one of the crucial n-6 fatty acids. The aim of this study was to investigate whether AA affects obesity through associating microbiota-driven inflammation with hypothalamus-adipose-liver axis. Four-week old C57BL/6 J mice were fed with a high-fat diet (HFD, 45% fat) for 10 weeks to induce obesity, and then fed a HFD enriched with 10 g/kg of AA or a continuous HFD in the following 15 weeks. Systemic adiposity and inflammation, metabolic profiles, gut microbiota composition, short-chain fatty acids production, hypothalamic feeding regulators, browning process of adipocytes, hepatosteatosis, and insulin resistance in adipose were investigated. The results indicated that AA aggravates obesity for both genders whereas sex-dependently affects gut microbiota composition. Also, AA favors pro-inflammatory microbiota and reduces butyrate production and circulating serotonin, which augments global inflammation and triggers hypothalamic leptin resistance via microglia accumulation in male. AA exacerbates non-alcoholic steatohepatitis along with amplified inflammation through TLR4-NF-κB pathway and induces insulin resistance. Reversely, AA alleviates obesity-related disorders via rescuing anti-inflammatory and butyrate-producing microbiota, up-regulating GPR41 and GPR109A and controlling hypothalamic inflammation in female. Nevertheless, AA modifies adipocyte browning and promotes lipid mobilization for both genders. We show that AA affects obesity likely through a gut-hypothalamus-adipose-liver axis. Our findings formulate recommendations of n-6 fatty acids like AA from dietary intake for obese subjects preferably in a sexually dimorphic way.

High mobility group box1 (HMGB1), as a damage-associated inflammatory factor, contributes to the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, we explored the role of HMGB1 in CDI (Clostridium difficile infection) by in vivo and in vitro experiments. Our results showed that HMGB1 might play an important role in the acute inflammatory responses to C. difficile toxin A (TcdA), affect early inflammatory factors, and induce inflammation via the HMGB1-TLR4 pathway. Our study provides the essential information for better understanding the molecular mechanisms of CDI and the potential new therapeutic strategies for the treatment of this infection.

探讨牛角瓜纤维混纺纱的开发要点.采用不同的混纺比,纺制了几种牛角瓜棉混纺纱和牛角瓜棉涤混纺纱,并对所纺混纺纱性能进行了测试分析.结果表明:随着牛角瓜纤维含量的增加,混纺纱强力和条干均变差;涤纶对条干均匀度改善较大;当牛角瓜纤维含量不超过40％时,纱线性能可以满足织造要求.认为:开发牛角瓜纤维混纺纱,除了要控制其混纺比外,还要选择性能及可纺性均较优的纤维品种与其混纺.

Disclosed are a method and a system for constructing a diploid monomer, relating to the bio-informatic field. The method comprises: a sequence fragment matrix M of m×n composed of a ternary character {A,B,C} is constructed by gathering all the sequence fragments containing at least one common site together; two fragment sets, S and T, are initialized according to the sequence fragment matrix M, S∪T=M and S∩T=Phi, wherein Phi represents a null set; an objective function zeta(S,T)=∑∑epsilon(M,i,j) and an initial reference temperature T0 are determined, wherein epsilon(M,i,j) represents the difference value between the total number of the same base types between the fragments i and j and the total number of the different base types between the fragments i and j; an annealing procedure is simulated based on the objective function and initial reference temperature T0, and the final sets S and T are output when convergence is achieved; and the haplotype h is deduced by a minimum error correction model according to the final sets S and T. The method and system for constructing a diploid monomer of the present invention can obtain a haplotype for a global optimal solution, and are high in accuracy and speed.

Abstract Background: The concept External Qi of Qigong refers to the technology and ability of “Qi deployment” therapy and health preservation of traditional Chinese medicine (TCM). External Qi therapy of TCM has long been one of the medical practices in China. Long-term clinical observations and ongoing studies have shown positive effects of external Qi of Yan Xin Qigong (YXQ-EQ) on cancer patients. Recently, the molecular and cellular mechanisms underlying YXQ-EQ's antitumor effects have begun to be addressed. In the present study we investigated YXQ-EQ's effects on growth, migration, invasion and apoptosis of estrogen-independent breast cancer MDA-MB-231 cells and the underlying molecular mechanisms. Methods: Cytotoxic effects were evaluated by trypan blue exclusion assay, MTS assay and/or clonogenic assay. Apoptosis was assessed by DNA fragmentation and cleavage of caspases and poly(ADP-ribose) polymerase. Quantitative analysis of apoptosis and cell cycle distribution was carried out by flow cytometry. Migration and invasion assay was performed in Transwell Boyden chambers and Matrigel-coated Boyden chambers, respectively. NF-κB activity was determined by electrophoresis mobility shift assay. Akt phosphorylation and NF-κB target gene expression was evaluated by Western blot analysis. Results: YXQ-EQ treatment of MDA-MB-231 cells induced a time-dependent reduction in viability, clonogenic growth inhibition, and apoptosis. Furthermore, YXQ-EQ blocked migration and invasion of MDA-MB-231 cells. Biochemically, YXQ-EQ markedly inhibited constitutive and EGF-induced Akt phosphorylation. YXQ-EQ also substantially repressed NF-κB activity, resulting in decreased expression of antiapoptotic Bcl-2, Bcl-XL, XIAP and survivin proteins. Conclusion: Our findings suggest that YXQ-EQ may induce apoptosis and inhibit migration and invasion of MDA-MB-231 cells through the repression of Akt/NF-κB signaling. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C155.