Effects of Auricularia auricula-judae (Bull.) Quél. polysaccharide acid hydrolysate on glucose metabolism in diabetic mice under oxidative stress.

BACKGROUND: Oxidative stress can lead to uncontrolled glucose metabolism and, thus, diabetes. Auricularia auricula-judae (Bull.) Quél. polysaccharides possess biological activities, such as antioxidant and hypoglycemic effects, but their mechanism of their acid hydrolysates on oxidative stress-injured glucose metabolism disorders is unclear. PURPOSE: Using diabetic mice, we investigated the effect of the acid hydrolysate of polysaccharides from Auricularia auricula-judae (Bull.) Quél. on improving diabetes. STUDY DESIGN AND METHODS: The structural information of sample polysaccharides was measured by high performance gel permeation chromatography, nuclear magnetic resolution, and high performance liquid chromatography. The diabetic model was established by intraperitoneal injection of streptozotocin. For eight consecutive weeks, the mice were orally administered sample polysaccharides (100, 200, and 300 mg/kg b.w. per day) for intervention. The improvement effect of the samples on diabetes was explored by detecting the changes in biochemical indicators in mice, and the underlying mechanism was studied by transcriptomic and metabolomic analysis. RESULTS: The results showed that acid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides consisted mainly of mannose, xylose, glucuronic acid, and glucose; its weight-averaged molecular weight was 6.3842 × 104 Dalton, its number average molecular weight was 2.9594 × 104 Dalton; and the molecule contained α-Glc(1→4)-, ß-Glc(1→3)-, and ß-Man(1→4)-linked glycosidic bonds. A total of 100 mg/kg b.w. per day sample was the best intervention concentration. After eight weeks of intervention, the sample polysaccharides significantly reduced dynamic blood glucose and serum lipids, enhanced antioxidant enzyme activities, promoted glucagon like peptide-1 and insulin secretion, improved insulin sensitivity and alleviated insulin resistance in diabetic mice. Transcriptomic and metabolomic analyses showed that sample polysaccharides was able to ameliorate disorders of glucose metabolism by modulating gene expression such as glucokinase; and modulate the state of oxidative stress in mice in vivo by regulating the glutathione metabolism pathway. CONCLUSION: Acid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides improved glucose metabolism disorders by slowing down the oxidative stress injury in mice, thereby alleviating diabetes. This study provided a basis for determining the underlying mechanism of the antidiabetic effect of Auricularia auricula-judae (Bull.) Quél. polysaccharides, which would significantly improve the deep development and application of these materials in diabetes control.

Liquid chromatography with tandem mass spectrometric method for determination of 52 antibiotics in human whole blood and urine and application to forensic cases.

PURPOSE: A rapid and reliable method was developed and validated for the simultaneous analysis of 52 antibiotics (cephalosporins, penicillins, carbapenems, lincosamides, quinolones, nitroimidazoles, macrolides, sulfonamides, tetracyclines, glycopeptide) in urine and whole blood by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). METHOD: Analytes were extracted by dilution or protein precipitation and analyzed on an Agilent 1260 HPLC system coupled to an Agilent 6470 Triple Quadrupole Mass Spectrometer. RESULTS: The method attended method validation criteria. The limits of detection were equal or lower than 2.0 ng/mL, whereas the limits of quantification ranged from 0.1 to 10.0 ng/mL, from 0.1 to 5.0 ng/mL, in urine and whole blood, respectively. For all analytes, the bias and intra- and inter-day precision values were less than 14.7%. The ranges of recovery values of all antibiotics were 76.5-124.5% in whole blood and 76.3-121.8% in urine, values of the effects were lower than 25% in two matrices. No evidence of carryover was observed. The study of sample stability showed that almost all analytes were stable at 24 °C for 24 h, all analytes were stable at -20 °C for 14 days and at -80 °C for 30 days. Freeze-thaw cycles stability showed that antibiotics were stable except for imipenem. Autosampler stability study showed that all analytes were stable for 24 h, except for imipenem and amoxicillin. Applicability was proven by analyzing authentic whole blood (n = 86) and urine (n = 79) samples from patients under antibiotics treatment. Therefore, this method was applied to the analysis 3 forensic allergy cases, which were positive for at least one analyte. CONCLUSIONS: A simple, sensitive and high-throughput method for the simultaneous determination of different classes of antibiotics in urine and whole blood samples was developed and applied. This sensitive method was successfully applied to forensic cases.

Melatonin attenuates fentanyl - induced behavioral sensitization and circadian rhythm disorders in mice.

Melatonin is a neurohormone synthesized by the pineal gland to regulate the circadian rhythms and has proven to be effective in treating drug addiction and dependence. However, the effects of melatonin to modulate the drug-seeking behavior of fentanyl and its underlying molecular mechanism is elusive. This study was designed to investigate the effects of melatonin on fentanyl - induced behavioral sensitization and circadian rhythm disorders in mice. The accompanying changes in the expression of Brain and Muscle Arnt-Like (BMAL1), tyrosine hydroxylase (TH), and monoamine oxidase A (MAO-A) in relevant brain regions including the suprachiasmatic nucleus (SCN), nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus (Hip) were investigated by western blot assays to dissect the mechanism by which melatonin modulates fentanyl - induced behavioral sensitization and circadian rhythm disorders. The present study suggest that fentanyl (0.05, 0.1 and 0.2 mg/kg) could induce behavioral sensitization and melatonin (30.0 mg/kg) could attenuate the behavioral sensitization and circadian rhythm disorders in mice. Fentanyl treatment reduced the expression of BMAL1 and MAO-A and increased that of TH in relevant brain regions. Furthermore, melatonin treatment could reverse the expression levels of BMAL1, MAO-A, and TH. In conclusion, our study demonstrate for the first time that melatonin has therapeutic potential for fentanyl addiction.

Screening of microalgae strains for efficient biotransformation of small molecular organic acids from dark fermentation biohydrogen production wastewater.

Dark fermentation biohydrogen production is a rapidly advancing and well-established field. However, the accumulation of volatile organic acid (VFAs) byproducts hinder its practical applications. Microalgae have demonstrated the ability to efficiently utilize VFAs while also treating waste gases and other nutrient elements. Integrating microalgae cultivation with dark fermentation is a promising approach. However, low VFAs tolerance and slow VFAs consumption restrict their application. To find suitable wastewater treatment microalgae, this work screened eight microalgae strains from five family. The results demonstrated that Chlamydomonas reinhardtii exhibited significant advantages in VFAs utilization, achieving a maximum removal of 100% for acetate and 52.5% for butyrate. Among the tested microalgae strains, CW15 outperformed in terms of photobioreactor adaptability, VFAs utilization, biomass productivity, and nutrient removal, making it the most promising microalgae for practical applications. This research demonstrates the feasibility of integrating microalgae cultivation with dark fermentation and providing a viable technical solution for integrated-biorefining.

Preparation of Auricularia auricula polysaccharides and their protective effect on acute oxidative stress injury of Caenorhabditis elegans.

This research enhanced the extraction procedure for Auricularia auricula crude polysaccharides by utilizing a modified Fenton reagent as a solvent, and obtained A. auricula polysaccharides (AAPs-VH) via alcohol precipitation and deproteinization. The HPLC profile revealed that the purified AAPs-VH using Sepharose 6FF was mainly a heteropolysaccharide, consisting primarily of mannose, glucuronic acid, glucose, and xylose. The Mw and Mn of the purified AAPs-VH were 87.646 kDa and 48.854 kDa, respectively. The FT-IR and NMR spectra revealed that the purified AAPs-VH belonged to pyranose and were mainly formed by (1 â†’ 3)-linked-ß-D glucan formation. In vivo experiments conducted with Caenorhabditis elegans, AAPs-VH was found to notably influence the lifespan, improve the antioxidant system, and decrease the level of cell apoptosis. This might be achieved by up-regulating the expression of genes in the IIS and TOR pathways. The study concludes that the modified Fenton reagent can increase Auricularia auricula polysaccharide solubleness and active sites, which may be an essential prompt for future studies.

Isolation, Characterization, and Antioxidant Activity of Melanin from Auricularia auricula (Agaricomycetes).

The cell wall of Auricularia auricula fruit bodies is extremely tough, making it difficult to dissolve the melanin using the traditional preparation method. To investigate the efficient preparation of melanin and its resistance to oxidative stress, this paper first used ultrasound-assisted alkaline cellulase to optimize the optimal wall-breaking parameters through a Box-Behnken design based on a single-factor experiment. After optimization, the yield of melanin from A. auricula reached 3.201 ± 0.018%. Then, different types and different proportions of deep eutectic solvents (DES) were used for further extraction. When choline chloride and urea were selected and the ratio was 1:2, the melanin yield was up to 25.99% ± 2.36%. Scanning electron microscope (SEM) images showed that the melanin was amorphous mass with no crystal structure. X-ray photoelectron spectroscopy (XPS) analysis revealed that the melanin was mainly composed of C (5.38%), O (15.69%) and N (30.29%), as was the typical composition of eumelanin. The melanin had a concentration-dependent relationship with both ABTS+ and hydroxyl radical scavenging ability; at the concentration of 0.5 mg/mL, it significantly prolonged Caenorhabditis elegans survival under hydrogen peroxide and methyl viologen stress and increased the glutathione level and enzyme (total superoxide dismutase and catalase) activities in vivo compared with the negative control (P < 0.05), indicating that the melanin enhances oxidative stress resistance in C. elegans.

Low-Grade Ductal Carcinoma in situ Within a Fibroadenoma of the Breast: A Rare Case Report and Review of the Literature.

Background: Ductal carcinoma in situ within a breast fibroadenoma is a rare malignancy with an incidence of only 0.02-0.125%. Imaging of low-grade ductal carcinoma in situ within a breast fibroadenoma shows no specific presentation. Therefore, pathology and immunohistochemistry are required for definitive diagnosis. Surgery is currently considered to be an effective treatment. There is no uniform clinical standard for postoperative adjuvant radiotherapy. Case Summary: A 60-year-old female patient underwent excisional biopsy on October 19, 2022. Pathology and immunohistochemistry confirmed the diagnosis of low-grade ductal carcinoma in situ within the fibroadenoma. Subsequently, breast-conserving surgery and sentinel lymph node biopsy were performed under general anesthesia with tracheal intubation, and no cancer metastasis was observed in the sentinel lymph nodes or incisional margins. Conclusion: Low-grade ductal carcinoma in situ within a breast fibroadenoma is an extremely rare malignancy, and clinicians should be familiar with its clinicopathological features and treatment methods. Multidisciplinary joint treatment is recommended to maximize the benefits to patients.

CCDC134 facilitates T cell activation through the regulation of early T cell receptor signaling.

Modulation of surface T cell antigen receptor (TCR) expression is crucial for proper T cell development and maintenance of mature T cell function at steady state and upon stimulation. We previously determined that CCDC134 (coiled-coil domain containing 134), a cytokine-like molecule that served as a potential member of the γc cytokine family, contributes to antitumor responses by augmenting CD8+ T cell-mediated immunity. Here we show that T cell-specific deletion of Ccdc134 decreased peripheral mature CD4+ and CD8+ T cells, which resulted in impaired T cell homeostasis. Moreover, Ccdc134-deficient T cells exhibited an attenuated response to TCR stimulation in vitro, showing lower activation and proliferative capacity. This was further reflected in vivo, rendering mice refractory to T cell-mediated inflammatory and antitumor responses. More importantly, CCDC134 is associated with TCR signaling components, including CD3ϵ, and attenuated TCR signaling in Ccdc134-deficient T cells via altered CD3ϵ ubiquitination and degradation. Taken together, these findings suggest a role for CCDC134 as a positive regulator of TCR-proximal signaling and provide insight into the cell-intrinsic functional consequences of Ccdc134 deficiency in the attenuation of T cell-mediated inflammatory and antitumor responses.

Biomimetic Mineralized Fiber Bundle-Inspired Scaffolding Surface on Polyetheretherketone Implants Promotes Osseointegration.

The stress shielding effect caused by traditional metal implants is circumvented by using polyetheretherketone (PEEK), due to its excellent mechanical properties; however, the biologically inert nature of PEEK limits its application. Endowing PEEK with biological activity to promote osseointegration would increase its applicability for bone replacement implants. A biomimetic study is performed, inspired by mineralized collagen fiber bundles that contact bone marrow mesenchymal stem cells (BMMSCs) on the native trabecular bone surface. The PEEK surface (P) is first sulfonated with sulfuric acid to form a porous network structure (sP). The surface is then encapsulated with amorphous hydroxyapatite (HA) by magnetron sputtering to form a biomimetic scaffold that resembles mineralized collagen fiber bundles (sPHA). Amorphous HA simulates the composition of osteogenic regions in vivo and exhibits strong biological activity. In vitro results show that more favorable cell adhesion and osteogenic differentiation can be attained with the novelsurface of sPHA than with SP. The results of in vivo experiments show that sPHA exhibits osteoinductive and osteoconductive activity and facilitates bone formation and osseointegration. Therefore, the surface modification strategy can significantly improve the biological activity of PEEK, facilitate effective osseointegration, and inspire further bionic modification of other inert polymers similar to PEEK.

The Biosafety Evaluation for Crustaceans: A Novel Molluscicide PBQ Using against Oncomelania hupensis, the Intermediate Host of Schistosoma japonica.

A new formulation (suspension concentrate, SC) of PBQ [1-(4-chlorophenyl)-3-(pyridin-3-yl) urea] was used in water network schistosomiasis-endemic areas to test its molluscicidal efficacy and the acute toxicity to crustaceans. PBQ (20% SC), 26% metaldehyde, and niclosamide suspension concentrate [MNSC (26% SC)] were used both in ditch and field experiments for the molluscicidal efficacy comparison. Acute toxicity tests of two molluscicides were conducted using Neocaridina denticulate and Eriocheir sinensis. Both in the field and ditch experiments, PBQ exhibited comparable molluscicidal efficacy with MNSC. At doses of 0.50 g/m3 and 0.50 g/m2, the snail mortalities were more than 90% three days after PBQ (20% SC) application. Compared with previous tests, PBQ (20% SC) exhibited higher molluscicidal activity than PBQ (25% wettable powder, 25% WP) used in Jiangling and showed similar mollucicidal activity to PBQ (25% WP) used in Dali and Poyang Lake. The 96 h LC50 value of MNSC against Eriocheir sinensis was 283.84 mg a.i./L. At the concentration of PBQ (20% SC) 1000 mg a.i./L, all Eriocheir sinensis were alive. The 96 h LC50 values of PBQ and MNSC against Neocaridina denticulate were 17.67 and 14.05 mg a.i./L, respectively. In conclusion, PBQ (20% SC) had a comparable molluscicidal efficacy with MNSC (26% SC) and PBQ (25% WP). Furthermore, it showed lower toxicity to the crustacean species, better solubility, no floating dust, and convenience for carriage. PBQ (20% SC) was suitable for controlling snails in the water network schistosomiasis-endemic areas.

Circadian rhythm promotes the biomass and amylose hyperaccumulation by mixotrophic cultivation of marine microalga Platymonas helgolandica.

BACKGROUND: Microalgal starch can be exploited for bioenergy, food, and bioplastics. Production of starch by green algae has been concerned for many years. Currently commonly used methods such as nutrient stress will affect cell growth, thereby inhibiting the production efficiency and quality of starch production. Simpler and more efficient control strategies need to be developed. RESULT: We proposed a novel regulation method to promote the growth and starch accumulation by a newly isolated Chlorophyta Platymonas helgolandica. By adding exogenous glucose and controlling the appropriate circadian light and dark time, the highest dry weight accumulation 6.53 g L-1 (Light:Dark = 12:12) can be achieved, and the highest starch concentration could reach 3.88 g L-1 (Light:Dark = 6:18). The highest production rate was 0.40 g L-1 d-1 after 9 days of production. And this method helps to improve the ability to produce amylose, with the highest accumulation of 39.79% DW amylose. We also discussed the possible mechanism of this phenomenon through revealing changes in the mRNA levels of key genes. CONCLUSION: This study provides a new idea to regulate the production of amylose by green algae. For the first time, it is proposed to combine organic carbon source addition and circadian rhythm regulation to increase the starch production from marine green alga. A new starch-producing microalga has been isolated that can efficiently utilize organic matter and grow with or without photosynthesis.

Comparison of the chemical composition and antioxidant stress ability of polysaccharides from Auricularia auricula under different drying methods.

Auricularia auricula fruiting body-derived polysaccharides (AAPs) were dried using different drying procedures, including hot air-, far infrared-, freeze-, and microwave-drying. The influences of different drying procedures on the chemical compositions and antioxidant activity in vitro and in vivo of AAPs were investigated. The results indicated that freeze-dried AAPs (AAPs-F) possessed the highest uronic acid content (33.53%) and the lowest molecular weight (406.77 kDa). Moreover, AAPs-F exhibited the most potent antioxidant abilities in vitro, including ABTS+ and DPPH˙ scavenging abilities, ferric reducing power, and metal ion chelating capacity. Besides, AAPs-F could significantly prolong the lifespan of wild-type C. elegans under oxidative stress induced by H2O2 and methyl viologen (p < 0.05) and upregulate the mRNA expression levels of daf-16 (>2.7 fold), sod-3 (>9.2 fold), skn-1 (>4.5 fold) and sir-2.1 (>1.9 fold), and play a significant role in protecting C. elegans against apoptosis (p < 0.05). Hence, freeze-drying was determined as the preferred procedure for obtaining high-quality AAPs.

Ccdc134 deficiency impairs cerebellar development and motor coordination.

Coiled-coil domain containing 134 (CCDC134) has been shown to serve as an immune cytokine to exert antitumor effects and to act as a novel regulator of hADA2a to affect PCAF acetyltransferase activity. While Ccdc134 loss causes abnormal brain development in mice, the significance of CCDC134 in neuronal development in vivo is controversial. Here, we report that CCDC134 is highly expressed in Purkinje cells (PCs) at all developmental stages and regulates mammalian cerebellar development in a cell type-specific manner. Selective deletion of Ccdc134 in mouse neural stem cells (NSCs) caused defects in cerebellar morphogenesis, including a decrease in the number of PCs and impairment of PC dendritic growth, as well as abnormal granule cell development. Moreover, loss of Ccdc134 caused progressive motor dysfunction with deficits in motor coordination and motor learning. Finally, Ccdc134 deficiency inhibited Wnt signaling but increased Ataxin1 levels. Our findings provide evidence that CCDC134 plays an important role in cerebellar development, possibly through regulating Wnt signaling and Ataxin1 expression levels, and in controlling cerebellar function for motor coordination and motor learning, ultimately making it a potential contributor to cerebellar pathogenesis.

Snoring frequency and risk of type 2 diabetes mellitus: a prospective cohort study.

OBJECTIVE: To evaluate the association between snoring frequency and type 2 diabetes mellitus (T2DM) according to age and gender in Chinese population. DESIGN: A cohort study was performed in Suzhou site of the China Kadoorie Biobank. Residents who didn't suffer from T2DM at baseline survey (2004-2008) and in half a year after baseline were enrolled in this study and followed cause-specific morbidity until 31 December 2013. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. Cox regression models were used to estimate HRs and 95% CIs for the snoring and T2DM association. SETTING: Wuzhong district, Suzhou, China. PARTICIPANTS: A total of 49 453 participants (men: 41.8%; mean age: 51.14±10.28 years) were enrolled in this study. OUTCOME MEASURES: T2DM cases were defined as International Classification of Diseases 10th Revision code of E11 and were identified through disease registries and health insurance databases. RESULTS: During a media of 7.18 years follow-up, 1120 T2DM cases were identified. Higher T2DM incidence was observed in participants with frequent and occasional snoring compared with those without (4.80 and 2.87 vs 2.39 per 1000 person-years). The multivariable-adjusted model found snoring was independently associated with T2DM (HR 1.28, 95% CI 1.20 to 1.38), both in men (HR 1.25, 95% CI 1.10 to 1.41) and women (HR 1.28, 95% CI 1.17 to 1.39). Moreover, a significant multiplicative interaction effect between snoring and age was detected on T2DM risk (p=0.015). CONCLUSIONS: Snoring was independently associated with an increased risk of T2DM in Chinese population, both in men and women. Meanwhile, there was an interaction effect between snoring and age on T2DM risk.

Laboratory Investigation of Renoxification from the Photolysis of Inorganic Particulate Nitrate.

Nitrogen oxides (NOx) play a key role in regulating the oxidizing capacity of the atmosphere through controlling the abundance of O3, OH, and other important gas and particle species. Some recent studies have suggested that particulate nitrate, which is conventionally considered as the ultimate oxidation product of NOx, can undergo "renoxification" via photolysis, recycling NOx and HONO back to the gas phase. However, there are large discrepancies in estimates of the importance of this channel, with reported renoxification rate constants spanning three orders of magnitude. In addition, previous laboratory studies derived the rate constant using bulk particle samples collected on substrates instead of suspended particles. In this work, we study renoxification of suspended submicron particulate sodium and ammonium nitrate through controlled laboratory photolysis experiments using an environmental chamber. We find that, under atmospherically relevant wavelengths and relative humidities, particulate inorganic nitrate releases NOx and HONO less than 10 times as rapidly as gaseous nitric acid, putting our measurements on the low end of recently reported renoxification rate constants. To the extent that our laboratory conditions are representative of the real atmosphere, renoxification from the photolysis of inorganic particulate nitrate appears to play a limited role in contributing to the NOx and OH budgets in remote environments. These results are based on simplified model systems; future studies should investigate renoxification of more complex aerosol mixtures that represent a broader spectrum of aerosol properties to better constrain the photolysis of ambient aerosols.

Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury.

Immunoglobulin (Igκ) has been reported to be expressed in sorted liver epithelial cells of µMT mice, and the sequence characteristics of hepatocyte-derived Igκ were different from those of classical B-cell-derived Igκ. However, the physiological function of hepatocyte-derived Igκ is still unclear. The expression of Igκ was firstly identified in primary hepatocytes and normal liver cell line (NCTC1469), and hepatocyte-derived Igκ expression was elevated and displayed unique localization in hepatocytes of concanavalin A (ConA)-induced hepatitis model. Moreover, Igκ knockout mice were more sensitive to ConA-induced hepatitis and had higher serum aspartate aminotransferase (AST) levels, more severe histological injury and a greater number of terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive cells as compared with littermate controls. Furthermore, knockdown of Igκ in primary hepatocytes and NCTC1469 cells led to accelerated activation of the mitochondrial death pathway and caspase-3 cleavage in vitro, which might be related to inhibition of NF-κB signaling pathway and activation of JNK via the cytoskeleton dynamics. Taken together, these results indicate that hepatocyte-derived Igκ mediates cellular resistance to ConA-induced liver injury by inhibiting activation of caspase-3 and the mitochondrial death pathway, suggesting that Igκ plays an important role in hepatocyte survival and exerts a protective effect against ConA-induced liver injury in mice.

Internal fat mediates the impact of age on diabetes onset in chinese people between 30 and 44 years old / La grasa interna media en el impacto de la edad sobre la aparición de diabetes en personas chinas de entre 30 y 44 años de edad

AIMS: We sought to measure the effect of controlling body fat indexes on decreasing the incidence of type 2 diabetes mellitus (T2DM) mathematically. METHODS: Study samples were selected from a well-established cohort in Suzhou, China between 2004 and 2008, comprising 6364 males and 9678 females. The questionnaire contained socio-demographic characteristics, smoking, alcohol consumption, diet, physical activity, personal and family medical history and current medication. Multiple linear regression, Cox regression and mediation analyses were performed to determine the relationship among age, body fat indexes and T2DM onset. RESULTS: All the three body fat indexes [the body mass index (BMI), waist-to-hip ratio (WHR) and body fat percentage] showed a significant positive association (P<0.05) with age and T2DM. Significant indirect effects (IE) were detected for age, which were mediated respectively through WHR [IE=1.10, 95%CI: 1.07-1.13; P<0.001], the BMI (IE=1.15, 95%CI: 1.11-1.18; P<0.001), and body fat percentage (IE=1.09, 95%CI: 1.07-1.12; P<0.001). The combined body fat index score demonstrated a significant association with age (P<0.001) and a stronger relationship with the onset of diabetes (P<0.001) along with a significant mediating effect (IE=1.17; 95%CI: 1.13-1.22; P<0.001). The total effect of age on T2DM was 1.60 (95%CI: 1.21-2.10; P=0.0008). As a result, the three body fat indexes jointly mediated 33.97% of the age impact on diabetes onset. CONCLUSIONS: This pilot study revealed important roles for body fat indexes in mediating the age pathway to the onset of diabetes. Controling body fat in the appropriate range could reduce 33.97% of the risk of T2DM onset with increasing age

OBJETIVOS: Medir matemáticamente el efecto del control de los índices de grasa corporal en la reducción de la incidencia de diabetes mellitus del tipo 2 (DMT2). MÉTODOS: Se obtuvieron durante 2004-2008 muestras para estudio de una cohorte bien establecida de Suzhou, China, formada por 6.364 varones y 9.678 mujeres. Mediante un cuestionario se recogieron los datos de las características sociodemográficas, el tabaquismo, el consumo de alcohol, la dieta, la actividad física, los antecedentes médicos personales y familiares y la medicación en curso. Se realizaron regresión lineal múltiple, regresión de Cox y análisis de mediación para determinar la relación entre edad, índices de grasa corporal y comienzo de la DMT2. RESULTADOS: Se halló una asociación positiva significativa (p < 0,05) de 3 índices de grasa corporal (índice de masa corporal [IMC], índice cintura-cadera [ICC] y porcentaje de grasa corporal) con la edad y la DMT2. Se detectaron efectos causales indirectos (EI) significativos de la edad, mediados respectivamente por el ICC (EI: 1,10; IC al 95%: 1,07-1,13; p < 0,001], el IMC (EI: 1,15; IC al 95%: 1,11-1,18; p < 0,001) y el porcentaje de grasa corporal (EI: 1,09; IC al 95%: 1,07-1,12; p < 0,001). La puntuación combinada de los índices de grasa corporal seguía mostrando una asociación significativa con la edad (p < 0,001) y una relación más intensa con el comienzo de la diabetes (p < 0,001), junto con un efecto mediador significativo (EI: 1,17; IC al 95%: 1,13-1,22; p < 0,001). El efecto total de la edad en la DMT2 era 1,60 (IC: 1,21-2,10; p = 0,0008). Como resultado, los 3 índices de grasa corporal fueron los mediadores del 33,97% de los efectos de la edad en el comienzo de la diabetes. CONCLUSIONES: Este estudio piloto reveló las importantes funciones de los índices de grasa corporal como mediadores del efecto de la edad en la aparición de la diabetes. El control de la grasa corporal dentro de límites apropiados podría reducir el 33,97% de riesgo de comienzo de la DMT2 con el paso de la edad

Internal fat mediates the impact of age on diabetes onset in chinese people between 30 and 44 years old.

AIMS: We sought to measure the effect of controlling body fat indexes on decreasing the incidence of type 2 diabetes mellitus (T2DM) mathematically. METHODS: Study samples were selected from a well-established cohort in Suzhou, China between 2004 and 2008, comprising 6364 males and 9678 females. The questionnaire contained socio-demographic characteristics, smoking, alcohol consumption, diet, physical activity, personal and family medical history and current medication. Multiple linear regression, Cox regression and mediation analyses were performed to determine the relationship among age, body fat indexes and T2DM onset. RESULTS: All the three body fat indexes [the body mass index (BMI), waist-to-hip ratio (WHR) and body fat percentage] showed a significant positive association (P<0.05) with age and T2DM. Significant indirect effects (IE) were detected for age, which were mediated respectively through WHR [IE=1.10, 95%CI: 1.07-1.13; P<0.001], the BMI (IE=1.15, 95%CI: 1.11-1.18; P<0.001), and body fat percentage (IE=1.09, 95%CI: 1.07-1.12; P<0.001). The combined body fat index score demonstrated a significant association with age (P<0.001) and a stronger relationship with the onset of diabetes (P<0.001) along with a significant mediating effect (IE=1.17; 95%CI: 1.13-1.22; P<0.001). The total effect of age on T2DM was 1.60 (95%CI: 1.21-2.10; P=0.0008). As a result, the three body fat indexes jointly mediated 33.97% of the age impact on diabetes onset. CONCLUSIONS: This pilot study revealed important roles for body fat indexes in mediating the age pathway to the onset of diabetes. Controling body fat in the appropriate range could reduce 33.97% of the risk of T2DM onset with increasing age.

Advances in the production of bioactive substances from marine unicellular microalgae Porphyridium spp.

Porphyridium spp. are a group of unicellular marine microalgae belonging to the Rhodophyta, which evolved over one billion years and are a source of a variety of natural active components. They can naturally and efficiently accumulate phycobilin, sulfated polysaccharides, polyunsaturated fatty acids and other bioactive substances. At present, numerous attempts have been made to explore the species Porphyridium spp., whereas mainly focused on cultivation methods, metabolism regulation and the function and application of bioactive products. There is a lack of systematic summary of the existing research conclusions. In this paper, we summarized the representative results related to culture and metabolism, analyzed and discussed the existing bottleneck restrictions for their large scale application, and proposed the potential industrial development and research direction in the future. This paper is expected to provide reference and thread for research and application of Porphyridium spp..

Seven-CpG-based prognostic signature coupled with gene expression predicts survival of oral squamous cell carcinoma.

BACKGROUND: DNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma. METHODS: A multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas (TCGA) data as training set which were validated in two independent datasets from Gene Expression Omnibus (GEO). The correlation between DNA methylation and corresponding gene expression and the prognostic value of the gene expression were explored as well. RESULTS: The seven DNA methylation CpG sites were identified which were significantly associated with OSCC overall survival. Prognostic signature, a weighted linear combination of the seven CpG sites, successfully distinguished the overall survival of OSCC patients and had a moderate predictive ability for survival [training set: hazard ratio (HR) = 3.23, P = 5.52 × 10-10, area under the curve (AUC) = 0.76; validation set 1: HR = 2.79, P = 0.010, AUC = 0.67; validation set 2: HR = 3.69, P = 0.011, AUC = 0.66]. Stratification analysis by human papillomavirus status, clinical stage, age, gender, smoking status, and grade retained statistical significance. Expression of genes corresponding to candidate CpG sites (AJAP1, SHANK2, FOXA2, MT1A, ZNF570, HOXC4, and HOXB4) was also significantly associated with patient's survival. Signature integrating of DNA methylation, gene expression, and clinical information showed a superior ability for prognostic prediction (AUC = 0.78). CONCLUSION: Prognostic signature integrated of DNA methylation, gene expression, and clinical information provides a better prognostic prediction value for OSCC patients than that with clinical information only.