Wild-type IDH2 is a therapeutic target for triple-negative breast cancer.

Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo. Genetic silencing or pharmacological inhibition of wt-IDH2 causes a significant increase in α-ketoglutarate (α-KG), indicating a suppression of reductive tricarboxylic acid (TCA) cycle. The aberrant accumulation of α-KG due to IDH2 abrogation inhibits mitochondrial ATP synthesis and promotes HIF-1α degradation, leading to suppression of glycolysis. Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.

Synthesis of urchin-like NiCo2S4 electrode materials based on a two-step hydrothermal method for high-capacitance supercapacitors.

Transition metal sulfides have been considered as promising electrode materials for future super-capacitors due to their spinel structures and environmentally friendly properties. Among these materials, NiCo2S4 compounds exhibit high theoretical specific capacity but poor cycling performance. To address this issue, we synthesize several NiCo2S4 urchin balls. The NCS-1.5 nanospheres demonstrate a specific capacitance of 1352.2 F g-1 at a current density of 1 A g-1, and maintain high specific capacity after 10 000 charge-discharge cycles. An asymmetric capacitor assembled with the NCS-1.5 sample as the cathode and activated carbon as the anode achieve an energy density of 45.5 W h kg-1 at 2025 W kg-1. The urchin-like nanospheres also facilitate the combination with other materials, providing potential insights for the synthesis of supercapacitor electrode materials.

Enhancing fuel characteristics and combustion performance of cellulose-rich straws through CO2-assisted torrefaction.

Cellulose-rich straws of corn and rice were torrefied under carbon dioxide, and the fuel characteristics and combustion performance of the obtained biochar were investigated. A high severity resulted in surface collapse, greater pore volume, elimination of oxygen, elevated calorific value, and improved hydrophobicity in biochar. Following carbon dioxide torrefaction, the cellulose content in solid biochar experienced a slight decrease when the temperature was raised to 220 °C for longer residence durations. At 300 °C, the cellulose content in the biochar was nearly eliminated, while the relative proportion of non-sugar organic matter in corn stover and rice straw increased to 87.40 % and 77.27 %, respectively. The maximum calorific values for biochar from corn and rice straws were 22.38 ± 0.03 MJ/kg and 18.72 ± 0.05 MJ/kg. The comprehensive combustion indexes of rice and corn straw samples decreased to 1.06 × 10-7 and 1.31 × 10-7 after torrefaction at 300 °C, respectively. In addition, the initial decomposition temperatures increased by 38 °C and 45 °C, while the ultimate combustion temperatures rose by 13 °C and 16 °C for corn and rice straws, respectively. These results imply an extended combustion timeframe for the torrefied samples.

Mechanisms of the PD-1/PD-L1 pathway in itch: From acute itch model establishment to the role in chronic itch in mouse.

Programmed cell death receptor/ligand 1 (PD-1/PD-L1) blockade therapy for various cancers induces itch. However, few studies have evaluated the mechanism underlying PD-1/PD-L1 inhibitor-induced itch. This study aimed to establish and evaluate a mouse model of acute itch induced by PD-1/PD-L1 inhibitors and to explore the role of the PD-1/PD-L1 pathway in chronic itch. The intradermal injection of the PD-1/PD-L1 small molecule inhibitors, or anti-PD-1/PD-L1 antibodies in the nape of the neck in the mice elicited intense spontaneous scratches. The model was evaluated using pharmacological methods. The number of scratches was reduced by naloxone but not by antihistamines or the transient receptor potential (TRP) channel inhibitor. Moreover, the PD-1 receptor was detected in the spinal cord of the mouse models of chronic itch that exhibited acetone, diethyl ether, and water (AEW)-induced dry skin, imiquimod-induced psoriasis, and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced allergic contact dermatitis. Intrathecal PD-L1 (1 µg, 4 times a week for 1 week) suppressed the activation of the microglia in the spinal dorsal horn to relieve the chronic itch that was elicited by imiquimod-induced psoriasis and DNFB-induced allergic contact dermatitis. Although the activation of the microglia in the spinal dorsal horn was not detected in the AEW-treated mice, intrathecal PD-L1 still reduced the number of scratches that were elicited by AEW. Our findings suggest that histamine receptor inhibitors or TRP channel inhibitors have limited effects on PD-1/PD-L1 inhibitor-induced itch and that spinal PD-1 is important for the spinal activation of the microglia, which may underlie chronic itch.

Impact of Beijing's "Coal to Electricity" program on ambient PM2.5 and the associated reactive oxygen species (ROS).

The Beijing "Coal to Electricity" program provides a unique opportunity to explore air quality impacts by replacing residential coal burning with electrical appliances. In this study, the atmospheric ROS (Gas-phase ROS and Particle-phase ROS, abbreviated to G-ROS and P-ROS) were measured by an online instrument in parallel with concurrent PM2.5 sample collections analyzed for chemical composition and cellular ROS in a baseline year (Coal Use Year-CUY) and the first year following implementation of the "Coal to Electricity" program (Coal Ban Year-CBY). The results showed PM2.5 concentrations had no significant difference between the two sampling periods, but the activities of G-ROS, P-ROS, and cellular ROS in CBY were 8.72 nmol H2O2/m3, 9.82 nmol H2O2/m3, and 2045.75 µg UD /mg PM higher than in CUY. Six sources were identified by factor-analysis from the chemical components of PM2.5. Secondary sources (SECs) were the dominant source of PM2.5 in the two periods, with 15.90% higher contribution in CBY than in CUY. Industrial Emission & Coal Combustion sources (Ind. & CCs), mainly from regional transport, also increased significantly in CBY. The contributions of Aged Sea Salt & Residential Burning sources to PM2.5 decreased 5.31% from CUY to CBY. The correlation results illustrated that Ind. & CCs had significant positive correlations with atmospheric ROS, and SECs significantly associated with cellular ROS, especially nitrates (r = 0.626, p = 0.000). Therefore, the implementation of the "Coal to Electricity" program reduced PM2.5 contributions from coal and biomass combustion, but had little effect on the improvement of atmospheric and cellular ROS.

Metabolic Flux Analysis Reveals the Roles of Stearate and Oleate on CPT1C-mediated Tumor Cell Senescence.

Cellular senescence is a state of proliferative arrest, and the development of carcinoma can be suppressed by conferring tumor cell senescence. Recently, we found that carnitine palmitoyltransferase 1C (CPT1C) controls tumor cell proliferation and senescence via regulating lipid metabolism and mitochondrial function. Here, 13C-metabolic flux analysis (13C-MFA) was performed and the results revealed that CPT1C knockdown in MDA-MB-231 cells significantly induced cellular senescence accompanied by altered fatty acid metabolism. Strikingly, stearate synthesis was decreased while oleate was increased. Furthermore, stearate significantly inhibited proliferation while oleate reversed the senescent phenotype induced by silencing CPT1C in MDA-MB-231 cells as well as PANC-1 cells. A939572, an inhibitor of stearoyl-Coenzyme A desaturase 1, had the same effect as stearate to inhibit cellular proliferation. These results demonstrated that stearate and oleate are involved in CPT1C-mediated tumor cellular senescence, and the regulation of stearate/oleate rate via inhibition of SCD-1 could be an additional strategy with depletion of CPT1C for cancer therapy.

Primary seminoma of prostate in a patient with Klinefelter syndrome: A case report.

RATIONALE: Klinefelter syndrome (KS) is a sex differentiation syndrome that occurs in men and is characterized by the 47XXY genotype. An association between KS and cancer has also been reported. The occurrence of seminoma of the prostate in KS has not been reported in the literature to date. Primary seminoma should be included in the differential diagnosis of prostate neoplasms in patients with KS. PATIENT CONCERNS: A 39-year-old man presenting with urinary retention was admitted to our hospital. Physical examination revealed sparse pubic hairs, atrophic testes, and an underdeveloped penis. Hormonal examination revealed significantly lowered serum testosterone levels and markedly higher follicle-stimulating hormone levels. A chromosomal examination was performed. Computed tomography and magnetic resonance imaging imaging showed a neoplasm in the left lobe of the prostate, and immunohistochemical examination of a transrectal needle biopsy of the prostate was performed. DIAGNOSES: Chromosomal examination was exhibited a 47 XXY genotype. Histopathology and of Immunohistochemistry of the transrectal needle biopsy specimen confirmed a seminoma. No other neoplasm was found on systemic examination; therefore, the patient was diagnosed with primary prostate seminoma and Klinefelter syndrome. INTERVENTIONS: The patient refused any treatment except catheterization because of religious reason. OUTCOMES: The patient died 2 years later. LESSONS: Primary seminoma should be included in the differential diagnosis of neoplasms of the prostate in patients with KS. Transrectal ultrasound-guided prostate needle biopsy is essential for the diagnosis of prostate neoplasms, and cisplatin-based chemotherapy remains the primary treatment for seminoma.

Evaluation of impact of "2+26″ regional strategies on air quality improvement of different functional districts in Beijing based on a long-term field campaign.

Consecutive measurements of ambient fine particulate matter (PM2.5) from February 2016 to April 2018 have been performed at four representative sites of Beijing to evaluate the impact of "2 + 26" regional strategies implemented in 2017 for air quality improvement in non-heating period (2017NH) and heating period (2017H). The decrease of PM2.5 were significant both in 2017NH (20.2% on average) and 2017H (43.7% on average) compared to 2016NH and 2016H, respectively. Eight sources were resolved at each site from the PMF source apportionment including secondary nitrate, traffic, coal combustion, soil dust, road dust, sulfate, biomass/waste burning and industrial process. The results show that the reductions of industrial process, soil dust, and coal combustion were most effective among all sources at each site after the regional strategies implementation with the large reductions in potential source areas. The decrease of coal combustion in 2017NH were larger than 2017H at all sites while that of soil dust and industrial sources were the opposite. Insignificant reduction of coal combustion contribution at the suburban site in the heating period indicated that rural residential coal burning need further control. The industrial source control in the suburbs were least effective compared with other districts. Traffic was the largest contributer at each site and control of traffic emissions were more effective in 2017H than 2017NH. The local nature and increase of biomass/waste burning contributions emphasized the effect of fireworks and bio-fuel use in rural areas and incinerator emissions in urban districts. Secondary nitrate and sulfate were mainly impacted by the regional transport from southern adjacent areas and favorable meteorological conditions played an important part in the PM2.5 abatements of 2017H. Secondary nitrate became a more major role in the air pollution process because of the larger decrease of sulfate. Finally suggestions for future control are made in this study.

Reductive TCA cycle catalyzed by wild-type IDH2 promotes acute myeloid leukemia and is a metabolic vulnerability for potential targeted therapy.

BACKGROUND: Isocitrate dehydrogenase-2 (IDH2) is a mitochondrial enzyme that catalyzes the metabolic conversion between isocitrate and alpha-ketoglutarate (α-KG) in the TCA cycle. IDH2 mutation is an oncogenic event in acute myeloid leukemia (AML) due to the generation of 2-hydroxyglutarate. However, the role of wild-type IDH2 in AML remains unknown, despite patients with it suffer worse clinical outcome than those harboring mutant type. METHODS: IDH2 expression in AML cell lines and patient samples was evaluated by RT-qPCR, western blotting and database analyses. The role of wild-type IDH2 in AML cell survival and proliferation was tested using genetic knockdown and pharmacological inhibition in AML cells and animal models. LC-MS, GC-MS, isotope metabolic tracing, and molecular analyses were performed to reveal the underlying mechanisms. RESULTS: We found that wild-type IDH2 was overexpressed in AML and played a major role in promoting leukemia cell survival and proliferation in vitro and in vivo. Metabolomic analyses revealed an active IDH2-mediated reductive TCA cycle that promoted the conversion of α-KG to isocitrate/citrate to facilitate glutamine utilization for lipid synthesis in AML cells. Suppression of wild-type IDH2 by shRNA resulted in elevated α-KG and decreased isocitrate/citrate, leading to reduced lipid synthesis, a significant decrease in c-Myc downregulated by α-KG, and an inhibition of AML viability and proliferation. Importantly, pharmacological inhibition of IDH2 showed significant therapeutic effect in mice inoculated with AML cells with wt-IDH2 and induced a downregulation of C-MYC in vivo. CONCLUSIONS: Wt-IDH2 is an essential molecule for AML cell survival and proliferation by promoting conversion of α-KG to isocitrate for lipid synthesis and by upregulating c-Myc expression and could be a potential therapeutic target in AML.

Inhibition of ultraviolet-induced sea cucumber (Stichopus japonicus) autolysis by maintaining coelomocyte intracellular calcium homeostasis.

Apoptosis plays a critical role in sea cucumber autolysis. To investigate the ultraviolet (UV)-induced apoptosis, sea cucumbers with and without injection of BAPTA-AM (cytosolic calcium chelator) were exposed to UV (15 W/m2) for 30 min. The results showed that UV irradiation caused several changes in sea cucumber coelomocytes, including calcium imbalance, abnormal morphology of endoplasmic reticulum, upregulation of pro-apoptotic proteins CRT, CHOP, and caspases 9 and 3, and downregulation of anti-apoptotic protein Bcl-2. A comparison between the two groups showed that injection of the calcium chelator into sea cucumbers helped maintain coelomocyte intracellular calcium homeostasis and suppressed other abnormal changes caused by ER stress, indicating apoptosis in sea cucumbers is mediated by calcium imbalance and follows the activation of the ER stress pathway. Therefore, this study broadens understanding of the apoptotic mechanism involved in sea cucumber autolysis, which is helpful in developing preservative agents for sea cucumbers.

Loss of mitochondrial aconitase promotes colorectal cancer progression via SCD1-mediated lipid remodeling.

OBJECTIVE: Mitochondrial aconitase (ACO2) is an essential enzyme that bridges the TCA cycle and lipid metabolism. However, its role in cancer development remains to be elucidated. The metabolic subtype of colorectal cancer (CRC) was recently established. We investigated ACO2's potential role in CRC progression through mediating metabolic alterations. METHODS: We compared the mRNA and protein expression of ACO2 between paired CRC and non-tumor tissues from 353 patients. Correlations between ACO2 levels and clinicopathological features were examined. CRC cell lines with knockdown or overexpression of ACO2 were analyzed for cell proliferation and tumor growth. Metabolomics and stable isotope tracing analyses were used to study the metabolic alterations induced by loss of ACO2. RESULTS: ACO2 decreased in >50% of CRC samples compared with matched non-tumor tissues. Decreased ACO2 levels correlated with advanced disease stage (P < 0.001) and shorter patient survival (P < 0.001). Knockdown of ACO2 in CRC cells promoted cell proliferation and tumor formation, while ectopic expression of ACO2 restrained tumor growth. Specifically, blockade of ACO2 caused a reduction in TCA cycle intermediates and suppression of mitochondrial oxidative phosphorylation, resulting in an increase in glycolysis and elevated citrate flux for fatty acid and lipid synthesis. Increased citrate flux induced upregulation of stearoyl-CoA desaturase (SCD1), which enhanced lipid desaturation in ACO2-deficent cells to favor colorectal cancer growth. Pharmacological inhibition of SCD selectively reduced tumor formation of CRC with ACO2 deficiency. CONCLUSIONS: Our study demonstrated that the rewiring metabolic pathway maintains CRC survival during compromised TCA cycles and characterized the therapeutic vulnerability of lipid desaturation in a meaningful subset of CRC with mitochondrial dysfunction.

Associations between source-resolved PM2.5 and airway inflammation at urban and rural locations in Beijing.

BACKGROUND: A large number of research studies have explored the health effects of exposure to atmospheric particulate matter. However, limited quantitative evidence has linked specific sources of personal PM2.5 directly to adverse health effects. This study was conducted in order to examine the association between airway inflammation and personal exposure to PM2.5 mass, components, and sources among two healthy cohorts living in both urban and rural areas of Beijing, China. METHODS: We conducted a follow-up study during the summer of 2016 and the winter of 2016/2017 among 92 students and 43 guards. 24-h personal and ambient exposure to PM2.5 and fractional exhaled nitric oxide (FeNO) were measured at least twice for each participant. Chemical components of 385 personal PM2.5 exposure samples were analyzed, and pollution sources were resolved by a positive matrix factorization (PMF) receptor model. We have constructed linear mixed effect models to evaluate the association between ambient/personal PM2.5 mass, chemical constituents, and source specific PM2.5 with FeNO after controlling for temperature, relative humidity, sites, season, and potential individual confounders. RESULTS: Interquartile range (IQR) increase in household heating sources was associated with increased FeNO (2.72%; 95% CI = 1.26-4.17%) across two sites. IQR increase in roadway transport was associated with increased FeNO (9.84%; 95% CI = 2.69-17%) in urban areas; IQR increase in Secondary inorganic sources and Industrial/Combustion sources were associated with increased FeNO (7.96%; 95% CI = 1.47-14.4%% and 7.85%; 95% CI = 0.0676-15.6%, respectively) in rural areas. Personal exposure to EC, OC, and some trace elements (Se, Pb, Bi, Cs) were also estimated to be significantly associated with the increase of FeNO. In addition, there was no significant difference (P > 0.05) between the effects of ambient and personal PM2.5 mass. CONCLUSIONS: Although personal PM2.5 mass was not significantly associated with the health effects, airway inflammation can be linked to source-resolved exposures.

Overexpression of GLT1D1 induces immunosuppression through glycosylation of PD-L1 and predicts poor prognosis in B-cell lymphoma.

B-cell non-Hodgkin's lymphoma (NHL) is a class of heterogeneous diseases with variable clinical outcomes. Immunosuppression is particularly common in the subtypes of lymphoma with poor prognosis, but the underlying mechanism remains unclear. Using a RT-PCR array analysis, we have identified that glycosyltransferase 1 domain-containing 1 (GLT1D1), an enzyme that transfers glycosyl groups to proteins, is highly upregulated in the incurable subtype of B-cell NHL and in early relapse diffuse large B-cell lymphoma. Analysis of clinical specimens revealed that GLT1D1 expression was positively correlated with the level of glycosylated programmed cell death-ligand 1 (PD-L1) in B-cell NHL and that high GLT1D1 expression was associated with poor prognosis. Mechanistically, we showed that GLT1D1 transferred N-linked glycans to PD-L1, thus promoting the immunosuppressive function of glycosylated PD-L1. Downregulation of GLT1D1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against lymphoma cells. In vivo, overexpression of GLT1D1 promoted tumor growth by facilitating tumor immune escape through increased levels of PD-L1. Our work has identified GLT1D1 as a predictive biomarker for B-cell NHL. It has also shown that this enzyme enhances PD-L1 stabilization via N-glycosylation, thus promoting immunosuppression and tumor growth. As such, GLT1D1 might be a novel therapeutic target for the treatment of B-NHL.

Metabolic reprogramming and redox adaptation in sorafenib-resistant leukemia cells: detected by untargeted metabolomics and stable isotope tracing analysis.

BACKGROUND: Internal tandem duplications (ITD) within the juxtamembrane domain of FMS-like tyrosine kinase 3 (FLT3) represent a poor prognostic indicator in acute myeloid leukemia (AML). Therapeutic benefits of tyrosine kinase inhibitors, such as sorafenib, are limited due to the emergence of drug resistance. While investigations have been conducted to improve the understanding of the molecular mechanisms underlying the resistance to this FLT3 inhibitor, a profile of cell functioning at the metabolite level and crosstalk between metabolic pathways has yet to be created. This study aimed to elucidate the alteration of metabolomic profile of leukemia cells resistant to the FLT3 inhibitor. METHODS: We established two sorafenib-resistant cell lines carrying FLT3/ITD mutations, namely the murine BaF3/ITD-R and the human MV4-11-R cell lines. We performed a global untargeted metabolomics and stable isotope-labeling mass spectrometry analysis to identify the metabolic alterations relevant to the therapeutic resistance. RESULTS: The resistant cells displayed fundamentally rewired metabolic profiles, characterized by a higher demand for glucose, accompanied by a reduction in glucose flux into the pentose phosphate pathway (PPP); and by an increase in oxidative stress, accompanied by an enhanced glutathione synthesis. We demonstrated that the highest scoring network of altered metabolites in resistant cells was related to nucleotide degradation. A stable isotope tracing experiment was performed and the results indicated a decrease in the quantity of glucose entering the PPP in resistant cells. Further experiment suggested that the inhibition of major enzymes in the PPP consist of glucose-6-phosphate dehydrogenase deficiency (G6PD) in the oxidative arm and transketolase (TKT) in the non-oxidative arm. In addition, we observed that chronic treatment with sorafenib resulted in an increased oxidative stress in FLT3/ITD-positive leukemia cells, which was accompanied by decreased cell proliferation and an enhanced antioxidant response. CONCLUSIONS: Our data regarding comparative metabolomics characterized a distinct metabolic and redox adaptation that may contribute to sorafenib resistance in FLT3/ITD-mutated leukemia cells.

Chemical characterization and source apportionment of PM2.5 personal exposure of two cohorts living in urban and suburban Beijing.

In the study, personal PM2.5 exposures and their source contributions were characterized for 159 subjects living in the Beijing Metropolitan area. The exposures and sources were examined as functions of residential location, season, vocation, cigarette smoking, and time spent outdoors. Sampling was performed for two categories of volunteers, guards and students, that lived in urban and suburban areas of Beijing. Samples were collected using portable PM2.5 monitors during summer and winter. Exposure measurements were supplemented with a questionnaire that tracked personal activity and time spent in microenvironments that may have impacted exposures. Simultaneously, ambient PM2.5 data were obtained from national network stations located at the Gucheng and Huairouzhen sites. These data were used as a comparison against the personal PM2.5 exposures and produced poor correlations between personal and ambient PM2.5. These results demonstrate that individual behavior strongly affects personal PM2.5 exposure. Six primary sources of personal PM2.5 exposure were determined using a positive matrix factorization (PMF) source apportionment model. These sources included Roadway Transport Source, Soil/Dust Source, Industrial/Combustion Source, Secondary Inorganic Source, Cd Source, and Household Heating Source. Averaged across all subjects and seasons, the highest source contribution was Secondary Inorganic Source (24.8% ±â€¯32.6%, AVG ±â€¯STD), whereas the largest primary ambient source was determined to be Roadway Transport (20.9% ±â€¯13.6%). Subjects were classified according to the questionnaire and were used to help understand the relationship between personal activity and source contribution to PM2.5 exposure. In general, primary ambient sources showed only significant spatial and seasonal differences, while secondary sources differed significantly between populations with different personal behavior. In particular, Cd source was found to be related to smoking exposure and was the most unpredictable source, with significant differences between populations of different sites, vocations, smoking exposures, and outdoor time.

Acute changes in a respiratory inflammation marker in guards following Beijing air pollution controls.

The adverse respiratory health effects of PM2.5 have been studied. However, the epidemiological evidence for the association of specific PM2.5 sources with health outcomes is still limited. This study investigated the association between PM2.5 components and sources with a biomarker of acute respiratory inflammation (FeNO) in guards. Personal exposure was estimated by microenvironment samplers and FeNO measurements were carried out before, during and after the Victory Day Military Parade in Beijing. Four sources were determined by factor analysis, including urban pollution, dust, alloy steel abrasion and toxic metals. A mixed-effect model was used to estimate the associations of FeNO with PM2.5 sources and chemical constituents, controlling for age, BMI, smoke activity, physical activity, waist circumference, temperature and relative humidity. In summary, large concentration decreases in PM2.5 concentration and PM2.5 chemical constituents were observed in both roadside and indoor environments during the air control periods, immediately followed by statistically significant decreases in FeNO of roadside guards and patrol guards. Besides, statistically significant increases in FeNO were found to be associated with interquartile range (IQR) increases in some pollutants, with an increase of 1.45ppb (95% CI: 0.69, 2.20), 0.65ppb (95% CI: 0.13, 1.17), 1.48ppb (95% CI: 0.60, 2.35), 0.82ppb (95% CI: 0.44, 1.20), 0.77ppb (95% CI: 0.42, 1.11) in FeNO for mass, sulfate, BC, Ca2+ and Sm, respectively. In addition, compared to alloy steel abrasion and toxic metals, urban pollution and dust factors were more associated with acute airway inflammation for highly-exposed populations.

Theacrine protects against nonalcoholic fatty liver disease by regulating acylcarnitine metabolism.

OBJECTIVE: Acylcarnitine metabolism disorder contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). There are, however, few ideal medications for NAFLD, which work by targeting acylcarnitine metabolism. The aim of this study was to investigate the protective effects of theacrine, a rare purine alkaloid isolated from Camellia assamica var. kucha, against acylcarnitine metabolism disorder in NAFLD. METHODS: The pharmacological activities of theacrine were studied using high-fat diet (HFD)-fed ApoE-/- and C57BL/6J mice models. Oleate-treated HepG2 and L-02 cells were used to investigate the molecular mechanism of theacrine on acylcarnitine metabolism. The target of theacrine was confirmed in vitro as the blockade of sirtuin 3 (SIRT3) and protein kinase A. RESULTS: Theacrine inhibits hepatic steatosis and liver inflammation and improves energy expenditure in HFD-fed mice. Theacrine ameliorates acylcarnitine metabolism disorder in HFD-fed mice and oleate-treated hepatocytes by improving fatty acid oxidation. The underlying mechanism involves theacrine's activation of the mitochondrial deacetylase SIRT3 and consequently, the increased activity of long-chain acyl coenzyme A dehydrogenase (LCAD) through deacetylation. CONCLUSION: Theacrine promotes acylcarnitine metabolism in NAFLD through the SIRT3/LCAD signaling pathway. The target of theacrine's activities on NAFLD is identified as SIRT3.

Rapid separation of non-polar and weakly polar analytes with metal-organic framework MAF-5 coated capillary column.

Metal-organic frameworks (MOFs) have attracted widespread attention due to their unique characters such as high surface area, high thermal and chemical stability, diverse structure topology and tunable pore size. The study first exploited a porous metal organic framework MAF-5 ([Zn[(eim)2], Heim=2-ethylimidazole) as stationary phase for gas chromatography by a novel dynamic coating method. The column efficiency of the 184 silicone@MAF-5 capillary column was up to 9045 plates m(-1) for benzene. The column is very promising for the rapid separation of polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs). And the column showed good reproducibility, retention time, peak area, high resolution, and a wide linear range. The determined thermodynamic parameters and chromatographic retention of all probe molecules on the 184 silicone@MAF-5 column showed the separation of analytes is a complex balance of thermodynamic and kinetic factors.

Application of nanomaterials in sample preparation.

Nanotechnology is one of the most important trends in material science. Due to the ultra-small size, nanomaterials possess unique physical and chemical properties. In this review, we summarized and discussed the recent applications of different nanomaterials, including metallic nanoparticles, metal organic frameworks (MOFs) materials, carbonaceous nanomaterials and siliceous nanoparticles, in sample preparation techniques.