Adenosine kinase inhibits ß-cell proliferation by upregulating DNA methyltransferase 3A expression.

AIM: To investigate the effects of adenosine kinase (ADK), a key enzyme in determining intracellular adenosine levels, on ß cells, and their underlying mechanism. METHODS: Genetic animal models and transgenic immortalized cells were applied to study the effect of ADK on islet beta-cell proliferation and function. The beta-cell mass and response to glucose were measured in vivo using mice with beta-cell-specific ADK overexpression, and in vitro using ADK-overexpressed immortalized beta-cell. RESULTS: The expression of ADK in human islets at high abundance, especially in ß cells, was decreased during the process of ß-cell proliferation. Additionally, a transgenic mouse model (ADKtg/tg /Mip-Cre) was generated wherein the mouse Insulin1 gene promoter specifically overexpressed ADK in pancreatic ß cells. The ADKtg/tg /Mip-Cre model exhibited impaired glucose tolerance, decreased fasting plasma insulin, loss of ß-cell mass, and inhibited ß-cell proliferation. Proteomic analysis revealed that ADK overexpression inhibited the expression of several proteins that promote cell proliferation and insulin secretion. Upregulating ADK in the ß-cell line inhibited the expression of ß-cell related regulatory molecules, including FoxO1, Appl1, Pxn, Pdx-1, Creb and Slc16a3. Subsequent in vitro experiments indicated that the inhibition of ß-cell proliferation and the decreased expression of Pdx-1, Creb and Slc16a3 were rescued by DNA methyltransferase 3A (DNMT3A) knockdown in ß cells. CONCLUSION: In this study, we found that the overexpression of ADK decreased the expression of several genes that regulate ß cells, resulting in the inhibition of ß-cell proliferation and dysfunction by upregulating the expression of DNMT3A.

Demographic and socioeconomic disparity in knowledge, attitude, and practice towards tuberculosis in Northwest, China: evidence from multilevel model study.

BACKGROUND: Tuberculosis (TB) remains a serious global public health problem in China. The right knowledge, attitude, and practice (KAP) towards TB are indispensable to appropriate healthcare-seeking behaviors and treatment services timely. However, there are few studies that addressed the KAP towards TB in high-risk and under-developing regions in China. This study aims to evaluate the KAP towards TB in Ningxia Northwest, China, and identify factors that influence it. The findings can guide future health education and promotion interventions. METHODS: A stratified multistage random sampling method was used to conduct a face-to-face questionnaire survey with 33 items for selected residents. The composite score of Knowledge, Attitudes, and Practices (KAP) was divided into two groups, which are poor (scores below the average) and good (scores above the average). A two-level logistic model with a random intercept equation accounted for the similarity of residents within communities to examine the association between individual-level KAP and demographic and socioeconomic factors. RESULTS: A total of 2,341 residents were recruited, the mean age was 50, and 41.2% were female. The percentages of residents who were total awareness of TB knowledge and had positive attitudes and behavior toward TB were 51.9%, 75.3%, and 76.2%, respectively. The two-level logistic model demonstrated that residents with a high annual family income, urban living, primary school education or higher, occupation of teacher or doctor, a very good self-perceived status, medical insurance, knowing DOTS, and family members or friends with TB history had better knowledge of TB (P < 0.05). Residents living in urban areas, with junior and senior high school education, a very good self-perceived status, health insurance, knowing DOTS, and family members or friends with TB history had positive attitude of TB (P < 0.05). Residents living in urban areas, a primary school education or higher, occupation of teacher, doctor and workers, a very good self-perceived status, medical insurance, knowing DOTS, and family members or friends with TB history had positive practice of TB (P < 0.05). CONCLUSIONS: Favorable demographic (higher education levels, teachers or doctors) and socioeconomic (high income, living in urban area) factors are associated to better knowledge, attitudes and practices toward TB in Northwest China. Interventions to improve KAP at the community level are required to speed up the TB reduction rate, which may benefit to ensure the End TB Strategy will be achieved.

Synthesis of ZSM-5 Zeolite Nanosheets with Tunable Silanol Nest Contents across an Ultra-wide pH Range and Their Catalytic Validation.

Zeolite synthesis under acidic conditions has always presented a challenge. In this study, we successfully prepared series of ZSM-5 zeolite nanosheets (Z-5-SCA-X) over a broad pH range (4 to 13) without the need for additional supplements. This achievement was realized through aggregation crystallization of ZSM-5 zeolite subcrystal (Z-5-SC) with highly short-range ordering and ultrasmall size extracted from the synthetic system of ZSM-5 zeolite. Furthermore, the crystallization behavior of Z-5-SC was investigated, revealing its non-classical crystallization process under mildly alkaline and acidic conditions (pH<10), and the combination of classical and non-classical processes under strongly alkaline conditions (pH≥10). What's particularly intriguing is that, the silanol nest content in the resultant Z-5-SCA-X samples appears to be dependent on the pH values during the Z-5-SC crystallization process rather than its crystallinity. Finally, the results of the furfuryl alcohol etherification reaction demonstrate that reducing the concentration of silanol nests significantly enhances the catalytic performance of the Z-5-SCA-X zeolite. The ability to synthesize zeolite in neutral and acidic environments without the additional mineralizing agents not only broadens the current view of traditional zeolite synthesis but also provides a new approach to control the silanol nest content of zeolite catalysts.

Excessive composite pollution carbon sources enhance the bio-fertilizer efficiency of Tetradesmus obliquus: focused on cultivation period.

Microalgae can use carbon sources in sludge extract prepared from sludge. Moreover, the high concentration of CO2 and the large number of carbon sources in the liquid phase will promote microalgae growth and metabolism. In this experiment, Tetradesmus obliquus was cultivated with sludge extract at 30% CO2. Algae liquid (the name used to describe the fertilizer made in this research) was further prepared as lettuce fertilizer. The effect of different times of microalgae culture (10, 15, 20, 25, and 30 days) on the fertilizer efficiency of the algae liquid was evaluated by lettuce hydroponic experiments. The findings indicate that lettuce cultivated in algae liquid collected on the 15th and 30th days exhibited superior performance in terms of growth, antioxidant capacity, and nutritional quality. We analyzed the experimental results in the context of microalgae metabolic mechanisms, aiming to contribute experience and data essential for the development of industrial microalgae fertilizer production.

Ectopic adrenocortical adenoma characterized by hypogonadism: a case report and review of the literature.

BACKGROUND: Currently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and localization diagnostic techniques. We report a typical case of ectopic adrenocortical adenomas and the data of treatment follow-up, and review the literature of 31 available cases of ectopic adrenocortical adenomas. CASE PRESENTATION: A 27-year-old Chinese female patient was admitted to our hospital for hypertension, hyperglycaemia and primary amenorrhea. The patient was functionally diagnosed with ACTH-independent CS and hypogonadotropic hypogonadism. Radiological evaluations, including Computed Tomography (CT) and functional imaging, identified a mass at the left renal hilum. Histological assessments post-surgical excision confirmed the mass to be an ectopic adrenocortical adenoma. A subsequent 3-month follow-up showed no signs of disease recurrence, a swift recovery of the cortisol axis was observed, with a partial recuperation of the gonadal axis. REVIEW: Our literature review shows that the most common ectopic areas of cortisol adenomas are renal hilum and hepatic region. The most positive biomarker is Melan A, and only a few cases have been diagnosed with functional localization. CONCLUSION: Ectopic adrenocortical adenomas may be asymptomatic in the early stage and can impact gonadal function. Physicians who treat hypogonadism must be aware of the need to test cortisol levels and perform functional localization in patients with lumps present.

Analysis of the regulatory mechanism of exogenous IAA-mediated tryptophan accumulation and synthesis of endogenous IAA in Chlorococcum humicola.

The activated sludge method is widely used for the treatment of phenol-containing wastewater, which gives rise to the problem of toxic residual sludge accumulation. Indole-3-acetic acid (IAA), a typical phytohormone, facilitates the microalgal resistance to toxic inhibition while promoting biomass accumulation. In this study, Chlorococcum humicola (C. humicola) was cultured in toxic sludge extract and different concentrations of IAA were used to regulate its physiological properties and enrichment of high value-added products. Ultimately, proteomics analysis was used to reveal the response mechanism of C. humicola to exogenous IAA. The results showed that the IAA concentration of 5 × 10-6 mol/L (M) was most beneficial for C. humicola to cope with the toxic stress in the sludge extract medium, to promote the activity of rubisco enzyme, to enhance the efficiency of photosynthesis, and, finally, to accumulate protein as a percentage of specific dry weight 1.57 times more than that of the control group. Exogenous IAA altered the relative abundance of various amino acids in C. humicola cells, and proteomic analyses showed that exogenous IAA stimulated the algal cells to produce more indole-3-glycerol phosphate (IGP), indole, and serine by up-regulating the enzymes. These precursors are converted to tryptophan under the regulation of tryptophan synthase (A0A383V983), and tryptophan can be metabolized to endogenous IAA to promote the growth of C. humicola. These findings have important implications for the treatment of toxic residual sludge while enriching for high-value amino acids.

Efficacy and Safety of Oxymatrine in the Treatment of Patients with Erythrodermic Psoriasis.

INTRODUCTION: The management of erythrodermic psoriasis (EP), a rare but severe type of psoriasis, is challenging, especially in patients with concomitant chronic hepatitis B (CHB). We previously demonstrated that oxymatrine treatment alleviated severe plaque psoriasis, but its therapeutic potential in treating EP remains unexplored. This study was to assess the efficacy and safety of oxymatrine for the treatment of EP, with attention to concomitant CHB. METHODS: In this investigator-initiated clinical trial, four consecutive patients with EP, including two (A and B) with concomitant CHB, were treated with intravenous administration of oxymatrine as monotherapy for 8 weeks, and scheduled to be followed up for a minimum of 24 weeks. The primary outcome was at least 75% improvement in the psoriasis area and severity index (PASI 75) at week 32. Secondary outcomes included the body surface area (BSA) score, dermatology life quality index (DLQI)], and safety. RESULTS: Patients A, B, and C achieved PASI 75 at treatment completion and week 32, demonstrating improvements of 77.4%, 97.2%, and 100% in PASI, respectively. Their BSA and DLQI were also improved significantly at week 32 and throughout follow-up of 37, 57, and 105 weeks, respectively. The viral loads in patients A and B with CHB decreased modestly. Patient D discontinued after follow-up for 19 weeks, and the primary outcome could not be analyzed. No adverse events were reported during treatment and follow-up. CONCLUSION: Oxymatrine appears to be efficacious and safe for the treatment of patients with EP, including those with concomitant CHB. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; Registration number ChiCTR-TRC-14004301).

Dicationic imidazole ionic liquid stationary phase for preservative detection and its application under mixed mode of HILIC/RPLC/IEC.

BACKGROUND: Food safety has always been a great concern, and the detection of additives is vital to ensuring food safety. Therefore, there is a necessity to develop a method that can quickly and efficiently separate and detect additives in food. High performance liquid chromatography is widely used in the analysis and testing of food additives. Ionic liquids have attracted wide attention in the preparation of high performance liquid chromatography stationary phases owing to their high stability, low vapor pressure and adjustable structure. RESULTS: We developed a novel dicationic imidazole ionic liquid stationary phase for the simultaneous determination of organic preservatives (sodium benzoate, potassium sorbate) and inorganic preservatives (nitrate and nitrite) in foodstuffs under mixed-mode chromatography. The method had the advantages of easy operation, high reproducibility, good linearity and precision. In the detection of these four preservatives, the limit of detection ≤0.4740 mg⋅L-1 and the limit of quantification ≤1.5800 mg⋅L-1. The intra-day and inter-day precision were less than 4.02%, and the recovery rate was 95.90∼100.19 %. At the same time, we also characterized the stationary phase, explored the mechanism and evaluated the chromatographic performance. The stationary phase was able to operate under the mixed mode of reversed phase/hydrophilic interaction/ion exchange chromatography, and it was capable of separating hydrophilic substances, hydrophobic substances, acids, and inorganic anionic substances with good separation efficiency and had high column efficiency. SIGNIFICANCE: In summary, the stationary phase has a promising application in the routine analysis of organic and inorganic preservatives in food. In addition, the stationary phase has good separation ability for hydrophilic, hydrophobic, ionic substances and complex samples, making it a prospective material for chromatographic separation.

Btbd8 deficiency reduces susceptibility to colitis by enhancing intestinal barrier function and suppressing inflammation.

Introduction: BTBD8 has been identified as a susceptible gene for inflammatory bowel diseases (IBD). However, the function of BTBD8 in normal development and IBD pathogenesis remains unknown. Methods: We administered drinking water with 3% dextran sodium sulfate (DSS) to wild-type (WT) and Btbd8 knockout (KO) mice for seven consecutive days to induce IBD. Subsequently, we further examined whether Btbd8 KO affects intestinal barrier and inflammation. Results: We demonstrated that Btbd8 deficiency partially protects mice from DSS-induced IBD, even though no obvious phenotypes were observed in Btbd8 KO mice. Btbd8 deletion leads to strengthened tight junctions between intestinal epithelial cells, elevated intestinal stem cell activity, and enhanced mucus layer. All these three mechanisms work together to improve the intestinal barrier integrity in Btbd8 KO mice. In addition, Btbd8 deficiency mitigates inflammation by reducing the expression of IL-1ß and IL-6 by macrophages. Discussion: Our studies validate the crucial role of Btbd8 in IBD pathogenesis, and reveal that Btbd8 deficiency may ameliorate DSS-induced IBD through improving the intestinal barrier integrity, as well as suppressing inflammatory response mediated by macrophages. These findings suggest that Btbd8 could be a promising therapeutic target for the treatment of IBD.

Preparation of dicationic ionic liquid modified silica stationary phase for mixed-mode liquid chromatography and its application for food additive detection.

BACKGROUND: Food safety has become an essential aspect of public concern and there are lots of detection means. Liquid chromatography plays a dominating role in food safety inspection because of its high separation efficiency and reproducibility. However, with the increasing complexity of real samples and monitoring requirements, conventional single-mode chromatography would require frequent column replacement and cannot separate different kinds of analytes on a single column simultaneously, which is costly and time-consuming. There is a great need for fabricating mixed-mode stationary phases and validating the feasibility of employing mixed-mode stationary phases for food safety inspection. RESULTS: This work fabricated multifunctional stationary phases for liquid chromatography to determine diverse food additives under the mixed mode of RPLC/HILIC/IEC. Two dicationic ionic liquid silanes were synthesized and bonded onto the silica gel surface. The functionalized silica was characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and elemental analysis. Both columns provide satisfactory separation performance towards 6 hydrophilic nucleosides, 4 hydrophobic polycyclic aromatic hydrocarbons, and 5 anions. Great repeatability of retention (RSD <0.1 %) and column efficiency (100330 plate/m) were obtained. Thermomechanical analysis and linear solvation energy relationship investigated the retention mechanism. Finally, the better in two prepared columns was employed to separate and determine the contents of NO2- and NO3- in vegetables(highest 4906 mg kg-1 NO3- in spinach), preservatives in bottled beverages (180.8 mg kg-1 sodium benzoate in soft drink), and melamine in milk with satisfactory performance and recovery rates ranging from 96.4 % to 105.6 %. SIGNIFICANCE: This work developed a novel scheme for preparing mixed-mode stationary phases by dicationic ionic liquid which provides great separation selectivity. Most importantly, this work proved the superiority of employing mixed-mode stationary phases for food safety inspection, which might avoid high-cost and frequent changes of columns and chromatography systems in the near future.