Genetic polymorphisms of CYP24A1 gene and cancer susceptibility: a meta-analysis including 40640 subjects.

BACKGROUND: Whether cytochrome P450 24A1 (CYP24A1) polymorphism is associated with cancer susceptibility, the individual study results are still controversial. Therefore, we performed a comprehensive study to identify the association of CYP24A1 polymorphisms (rs4809960, rs6068816, rs2296241, rs4809957, rs2762939) with cancer susceptibility. METHODS: Electronic databases including Cochrane Library, PubMed, and Embase were systematically retrieved for relevant publications. Fixed or random-effect model was selected to calculate odds ratios (ORs) with their 95% confidence intervals (95%CI). RESULTS: Eighteen published articles were identified. The results indicated that rs4809960 polymorphism was associated with a decreased cancer risk in Caucasian (TT vs. TC+CC: P=0.035; C vs. T: P=0.016) and Asian population (CC vs. TC+TT: OR P=0.044; TT vs. TC+CC: P=0.021; CC vs. TT: P=0.020; C vs. T: P=0.008) and breast cancer risk (TT vs. TC+CC: P = 0.007; TC vs. TT: P=0.004; C vs. T: P=0.033). A significant association was found between rs2296241 polymorphism and esophageal squamous cell carcinoma risk (AA vs. GG+AG: P = 0.023) and prostate cancer susceptibility (A vs. G: P=0.022). Furthermore, rs4809957 polymorphism was associated with prostate cancer susceptibility in Caucasian (GG vs. GA+AA: P=0.029; GA vs. GG: P=0.022) and breast cancer susceptibility (AA vs. GG+GA: P=0.012; AA vs. GG, P=0.010; A vs. G: P=0.024). Additionally, rs6068816 polymorphism significantly decreased the lung cancer (CC vs. CT+TT: P = 0.016; TT vs. CC: P = 0.044; CT vs. CC: P = 0.036; T vs. C: P = 0.016) and breast cancer risk (TT vs. CC+CT: P = 0.043; TT vs. CC: P = 0.039). No association was found for rs2762939 polymorphism with overall cancer risk. However, for rs2296241, rs4809957, and rs6068816 polymorphisms, there were no significant differences after the Bonferroni correction. CONCLUSION: The meta-analysis suggested that rs4809960 was associated with cancer risk and might be a genetic marker for predicting cancer risk. More large-scale and large-sample studies are necessary to further confirm these results.

Serum glial cell line-derived neurotrophic factor (GDNF) a potential biomarker of executive function in Parkinson's disease.

Objective: Evidence shows that the impairment of executive function (EF) is mainly attributed to the degeneration of frontal-striatal dopamine pathway. Glial cell line-derived neurotrophic factor (GDNF), as the strongest protective neurotrophic factor for dopaminergic neurons (DANs), may play a role in EF to some extent. This study mainly explored the correlation between serum GDNF concentration and EF performance in Parkinson's disease (PD). Methods: This study recruited 45 healthy volunteers (health control, HC) and 105 PD patients, including 44 with mild cognitive impairment (PD-MCI), 20 with dementia (PD-D), and 20 with normal cognitive function (PD-N). Neuropsychological tests were performed to evaluate EF (working memory, inhibitory control, and cognitive flexibility), attention, language, memory, and visuospatial function. All subjects were tested for serum GDNF and homovanillic acid (HVA) levels by ELISA and LC-ESI-MS/MS, respectively. Results: PD-MCI patients showed impairments in the trail making test (TMT) A (TMT-A), TMT-B, clock drawing test (CDT) and semantic fluency test (SFT), whereas PD-D patients performed worse in most EF tests. With the deterioration of cognitive function, the concentration of serum GDNF and HVA in PD patients decreased. In the PD group, the serum GDNF and HVA levels were negatively correlated with TMT-A (r GDNF = -0.304, P < 0.01; r HVA = -0.334, P < 0.01) and TMT-B (r GDNF = -0.329, P < 0.01; r HVA = -0.323, P < 0.01) scores. Serum GDNF levels were positively correlated with auditory verbal learning test (AVLT-H) (r = 0.252, P < 0.05) and SFT (r = 0.275, P < 0.05) scores. Serum HVA levels showed a positively correlation with digit span test (DST) (r = 0.277, P < 0.01) scores. Stepwise linear regression analysis suggested that serum GDNF and HVA concentrations and UPDRS-III were the influence factors of TMT-A and TMT-B performances in PD patients. Conclusion: The decrease of serum GDNF concentration in PD patients was associated with impaired inhibitory control, cognitive flexibility, and attention performances. The changes of GDNF and HVA might synergistically participate in the occurrence and development of executive dysfunction in PD patients.

Application of Metal-Organic Frameworks (MOFs) in Environmental Biosystems.

Metal-organic frameworks (MOFs) are crystalline materials that are formed by self-assembling organic linkers and metal ions with large specific areas and pore volumes. Their chemical tunability, structural diversity, and tailor-ability make them adaptive to decorate many substrate materials, such as biomass-derived carbon materials, and competitive in many environmental biosystems, such as biofuel cells, bioelectrocatalysts, microbial metal reduction, and fermentation systems. In this review, we surmised the recent progress of MOFs and MOF-derived materials and their applications in environmental biosystems. The behavior of MOFs and MOF-derived materials in different environmental biosystems and their influences on performance are described. The inherent mechanisms will guide the rational design of MOF-related materials and lead to a better understanding of their interaction with biocomponents.

Research progress on molecular biomarkers of acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common type of adult acute leukemia. The pathophysiology of the disease has been studied intensively at the cellular and molecular levels. At present, cytogenetic markers are an important basis for the early diagnosis, prognostic stratification and treatment of AML. However, with the emergence of new technologies, the detection of other molecular markers, such as gene mutations and epigenetic changes, began to play important roles in evaluating the occurrence and development of diseases. Recent evidence shows that identifying new AML biomarkers contributes to a better understanding of the molecular mechanism of the disease and is essential for AML screening, diagnosis, prognosis monitoring, and individualized treatment response. In this review, we summarized the promising AML biomarkers from four aspects, which contributing to a better understanding of the disease. Of course, it must be soberly aware that we have not listed all biomarkers of AML. Anyway, the biomarkers we mentioned are representative. For example, mutations in TP53, FLT3, and ASXL1 suggest poor prognosis, low remission rate, short survival period, and often require allogeneic hematopoietic stem cell transplantation. The CEBPA double mutation, NPM1 and CBF mutation suggest that the prognosis is good, the remission rate is high, the survival period is long, and the effect of chemotherapy or autotherapy is good. As for other mutations mentioned in the article, they usually predict a moderate prognosis. All in all, we hope it could provide a reference for the precise diagnosis and treatment of AML.

Effects of photodynamic therapy on Streptococcus mutans and enamel remineralization of multifunctional TiO2-HAP composite nanomaterials.

BACKGROUND: As photosensitizer and photocatalyst, titanium dioxide (TiO2) can produce a photodynamic reaction for antibacterial treatment. This study aims to explore a Titanium dioxide/nano-hydroxyapatite (TiO2-HAP) composite combined with the dental curing lamp (385-515 nm) in clinical which could inhibit the dental plaque biofilm formed by Streptococcus mutans (S. mutans) and promote the enamel surface remineralization simultaneously. METHODS: X-ray Diffraction (XRD) and high resolution transmission electron microscope (HRTEM) were used to detect the characterization of TiO2-HAP composite nanomaterials. Photodynamic properties of TiO2-HAP were detected by Diffuse reflectance spectrum (DRS) and fluorescence spectroscopy. Bacterial growth was measured by reading the absorbance of bacterial cultures and confocal microscope was used to observe the biofilm removal ability of nanomaterials. The ability of TiO2-HAP to promote enamel remineralization was measured by Scanning electron microscope (SEM). RESULTS: The OD 600 of S. mutans was 0.76 in the control group and 0.13 in group of TiO2-HAP with exposure to light-emitting diode (LED) (150 mW/cm2) for 5 min, suggesting its sustained antibacterial potency and inhibition of the metabolic activity of dental plaque microcosm biofilm. Also, the release of calcium and phosphorus ions in TiO2-HAP can promote enamel mineralization simultaneously. After 15 days of remineralization, the Ca/P ratio of demineralized enamel surface increased from 1.28 to 1.67, which was similar to that of normal enamel. CONCLUSIONS: The TiO2-HAP exhibit a promising anti-bacterial activity and remineralization capacity which can prevent the occurrence of caries to the greatest extent and promote the biomimetic mineralization of dental tissues.

Cost-effectiveness analysis of rhTPO and rhIL-11 in the treatment of chemotherapy-induced thrombocytopenia in hematological tumors based on real-world data.

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a common adverse reaction to chemotherapy that can lead to treatment delay, platelet transfusion, thereby increasing treatment costs, reducing chemotherapy effectiveness and affecting prognosis. Based on real-world data, this study analyzed the safety, efficacy, and economic of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of CIT in hematological tumors from the perspective of the health care system. METHODS: We retrospectively collected the data of hematological tumor patients treated with rhTPO and rhIL-11 due to thrombocytopenia caused by chemotherapy. The propensity score matching (PSM) method was used to balance the baseline information of the two groups and they were further stratified according to the degree of thrombocytopenia (grade I-II and grade III-IV). The platelet compliance rate at 2 weeks of treatment was used as the efficacy evaluation index, and the cost-effectiveness method was used to evaluate the economic value of the two drugs in the treatment of thrombocytopenia based on drug effectiveness. Univariate and probabilistic sensitivity analyses were performed. RESULTS: A total of 1,571 patients met the inclusion and exclusion criteria, and 476 patients were included after 1:1 PSM. For patients with grade I-II thrombocytopenia, no significant difference in the platelet compliance rate was found between the two groups after 1 and 2 weeks of treatment. The platelet compliance rate in the rhTPO group was higher than that in the rhIL-11 group for patients with grade III-IV thrombocytopenia. Cost-effectiveness analysis (CEA) showed that the incremental cost-effectiveness ratio (ICER) for the rhTPO and rhIL-11 groups was 226,615.8. The ICER value was sensitive to the platelet compliance rate of the two groups, the cost of rhTPO, the cost of platelet transfusion in the rhTPO group. Probabilistic sensitivity analysis showed that when willingness to pay was less than approximately 220,000 yuan, rhIL-11 economy presented 100% better than that of rhTPO. CONCLUSIONS: In CIT treatment for hematological tumors, rhTPO yielded a higher platelet compliance rate than rhIL-11 treatment, especially for patients with grade III-IV thrombocytopenia. However, whether rhTPO has economic advantages still requires further exploration.

High-performance free-standing microbial fuel cell anode derived from Chinese date for enhanced electron transfer rates.

Traditional anode materials have disadvantages like low specific surface area and poor electrical conductivity. Herein, carbonized Chinese dates (CCD) were synthesized as microbial fuel cells (MFC) anodes. The obtained materials exhibited excellent biocompatibility with fast start-up (within one day) and charge transfer (Rct 4.0 Ω). Their porous structure allows efficient ion transport and microbial community succession, favorable for long-term operation. The biomass analysis shows that CCD anodes can load higher weight of biomass. High-throughput sequencing (16S rRNA) discovered that CCD anode can enrich Geobacter spp., with highest abundance of 73.4%, much higher than carbon felt (CF, 39.2%). Benefit from these properties, the MFC with CCD anodes possess a maximum power density of 12.17 W m-3 (1.62 times of commercial carbon felt). In all, the CCD anode exhibits high performance with low cost and easy fabrication, certificating it a promising candidate for an ideal MFC anode material.

Insights into high concentrations of particle-bound imidazoles in the background atmosphere of southern China: Potential sources and influencing factors.

Imidazoles are important constituents in atmospheric brown carbon and have gained increasing attention in the past decade. Although imidazoles have been studied widely in laboratories, the sparse field observations severely limit the understanding of imidazole's abundance and sources in the atmosphere. In this study, we measured particle-bound imidazoles and their precursors at a background forest site in the Nanling Mountains of southern China. The average concentration of imidazoles (4.17 ± 3.76 ng/m3) was found to be significantly higher than other background sites worldwide. Further analyses revealed that a majority of imidazoles (59.1%) at the site originated from secondary formation through reactions of dicarbonyls (e.g., glyoxal and methylglyoxal) and reduced nitrogen species, with relatively minor contributions from regional transport (32.8%) and biomass burning (8.1%). In addition, the key factors influencing secondary formation of imidazoles, such as relative humidity, water-soluble inorganic ions, and pH, were analyzed. Our results indicated that the secondary formation of imidazoles can be greatly enhanced under high humidity conditions, particularly during fog events. Overall, this study offers valuable insights into potential sources and influencing factors of ambient imidazoles in background atmospheres.

Activation of TAF9 via Danshensu-Induced Upregulation of HDAC1 Expression Alleviates Non-alcoholic Fatty Liver Disease.

Fatty acid ß-oxidation is an essential pathogenic mechanism in nonalcoholic fatty liver disease (NAFLD), and TATA-box binding protein associated factor 9 (TAF9) has been reported to be involved in the regulation of fatty acid ß-oxidation. However, the function of TAF9 in NAFLD, as well as the mechanism by which TAF9 is regulated, remains unclear. In this study, we aimed to investigate the signaling mechanism underlying the involvement of TAF9 in NAFLD and the protective effect of the natural phenolic compound Danshensu (DSS) against NAFLD via the HDAC1/TAF9 pathway. An in vivo model of high-fat diet (HFD)-induced NAFLD and a palmitic acid (PA)-treated AML-12 cell model were developed. Pharmacological treatment with DSS significantly increased fatty acid ß-oxidation and reduced lipid droplet (LD) accumulation in NAFLD. TAF9 overexpression had the same effects on these processes both in vivo and in vitro. Interestingly, the protective effect of DSS was markedly blocked by TAF9 knockdown. Mechanistically, TAF9 was shown to be deacetylated by HDAC1, which regulates the capacity of TAF9 to mediate fatty acid ß-oxidation and LD accumulation during NAFLD. In conclusion, TAF9 is a key regulator in the treatment of NAFLD that acts by increasing fatty acid ß-oxidation and reducing LD accumulation, and DSS confers protection against NAFLD through the HDAC1/TAF9 pathway.

Variation of Two S3b Residues in KV4.1-4.3 Channels Underlies Their Different Modulations by Spider Toxin κ-LhTx-1.

The naturally occurred peptide toxins from animal venoms are valuable pharmacological tools in exploring the structure-function relationships of ion channels. Herein we have identified the peptide toxin κ-LhTx-1 from the venom of spider Pandercetes sp (the Lichen huntsman spider) as a novel selective antagonist of the KV4 family potassium channels. κ-LhTx-1 is a gating-modifier toxin impeded KV4 channels' voltage sensor activation, and mutation analysis has confirmed its binding site on channels' S3b region. Interestingly, κ-LhTx-1 differently modulated the gating of KV4 channels, as revealed by toxin inhibiting KV4.2/4.3 with much more stronger voltage-dependence than that for KV4.1. We proposed that κ-LhTx-1 trapped the voltage sensor of KV4.1 in a much more stable resting state than that for KV4.2/4.3 and further explored the underlying mechanism. Swapping the non-conserved S3b segments between KV4.1(280FVPK283) and KV4.3(275VMTN278) fully reversed their voltage-dependence phenotypes in inhibition by κ-LhTx-1, and intensive mutation analysis has identified P282 in KV4.1, D281 in KV4.2 and N278 in KV4.3 being the key residues. Furthermore, the last two residues in this segment of each KV4 channel (P282/K283 in KV4.1, T280/D281 in KV4.2 and T277/N278 in KV4.3) likely worked synergistically as revealed by our combinatorial mutations analysis. The present study has clarified the molecular basis in KV4 channels for their different modulations by κ-LhTx-1, which have advanced our understanding on KV4 channels' structure features. Moreover, κ-LhTx-1 might be useful in developing anti-arrhythmic drugs given its high affinity, high selectivity and unique action mode in interacting with the KV4.2/4.3 channels.

Electroconvulsive therapy is associated with lower readmission rates in patients with schizophrenia.

BACKGROUND: Electroconvulsive therapy is an important somatic treatment for severe mental disorders with established efficacy and safety. However, data on the relationship between ECT and the readmission rate of patients with schizophrenia are scarce. This study will explore the association between the administration of ECT and readmission rates using a machine learning method. METHODS: Inpatient medical records from the year of 2016 in one large psychiatric hospital in Beijing, China, were analyzed using a machine learning algorithm to determine the most important variables affecting readmission of patients with schizophrenia. RESULTS: The medical records of 2131 inpatients with schizophrenia were reviewed. 1099 patients were followed up within 3 months of their index admission (642 ECT cases and 457 non-ECT cases) and 1032 patients were followed up within 6 months (596 ECT cases and 436 non-ECT cases) after discharge. The 3- and 6-month readmission rates in the ECT group (11.37% and 17.94%, respectively) were significantly lower than that of the patients who did not receive ECT (18.79% and 29.36%, respectively, both p < 0.001). The risk of readmission was significantly associated with male sex, older age, being married, having a lower income, a shorter inpatient length of stay, and receiving specific antipsychotic medications including olanzapine, paliperidone, clozapine, and haloperidol during the index admission. In the ECT group, patients who received 9 or more treatments were significantly less likely to be readmitted. CONCLUSION: Receiving ECT may be associated with a lower risk of readmission in patients with schizophrenia.

Cost-effectiveness of CYP2C19 genotyping to guide antiplatelet therapy for acute minor stroke and high-risk transient ischemic attack.

Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin within 48 h of acute minor strokes and transient ischemic attacks (TIAs) has been indicated to effectively reduce the rate of recurrent strokes. However, the efficacy of clopidogrel has been shown to be affected by cytochrome P450 2C19 (CYP2C19) polymorphisms. Patients carrying loss-of-function alleles (LoFAs) at a low risk of recurrence (ESRS < 3) cannot benefit from clopidogrel plus aspirin at all and may have an increased bleeding risk. In order to optimize antiplatelet therapy for these patients and avoid the waste of medical resources, it is important to identify the subgroups that genuinely benefit from DAPT with clopidogrel plus aspirin through CYP2C19 genotyping. This study sought to assess the cost-effectiveness of CYP2C19 genotyping to guide drug therapy for acute minor strokes or high-risk TIAs in China. A decision tree and Markov model were constructed to evaluate the cost-effectiveness of CYP2C19 genotyping. We used a healthcare payer perspective, and the primary outcomes included quality-adjusted life years (QALYs), costs and the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to evaluate the robustness of the results. CYP2C19 genotyping resulted in a lifetime gain of 0.031 QALYs at an additional cost of CNY 420.13 (US$ 59.85), yielding an ICER of CNY 13,552.74 (US$ 1930.59) per QALY gained. Probabilistic sensitivity analysis showed that genetic testing was more cost-effective in 95.7% of the simulations at the willingness-to-pay threshold of CNY 72,100 (GDP per capita, US$ 10,300) per QALY. Therefore, CYP2C19 genotyping to guide antiplatelet therapy for acute minor strokes and high-risk TIAs is highly cost-effective in China.

Resistin-like molecule ß acts as a mitogenic factor in hypoxic pulmonary hypertension via the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK signaling pathways.

BACKGROUND: Pulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule ß (RELM-ß) is upregulated de novo in response to hypoxia in cultured human PASMCs (hPASMCs). RELM-ß has been reported to promote hPASMC proliferation and is involved in pulmonary vascular remodeling in patients with PAH. However, the expression pattern, effects, and mechanisms of action of RELM-ß in HPH remain unclear. METHODS: We assessed the expression pattern, mitogenetic effect, and mechanism of action of RELM-ß in a rat HPH model and in hPASMCs. RESULTS: Overexpression of RELM-ß caused hemodynamic changes in a rat model of HPH similar to those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), right ventricular hypertrophy index (RVHI) and thickening of small pulmonary arterioles. Knockdown of RELM-ß partially blocked the increases in mRVSP, RVHI, and vascular remodeling induced by hypoxia. The phosphorylation levels of the PI3K, Akt, mTOR, PKC, and MAPK proteins were significantly up- or downregulated by RELM-ß gene overexpression or silencing, respectively. Recombinant RELM-ß protein increased the intracellular Ca2+ concentration in primary cultured hPASMCs and promoted hPASMC proliferation. The mitogenic effects of RELM-ß on hPASMCs and the phosphorylation of PI3K, Akt, mTOR, PKC, and MAPK were suppressed by a Ca2+ inhibitor. CONCLUSIONS: Our findings suggest that RELM-ß acts as a cytokine-like growth factor in the development of HPH and that the effects of RELM-ß are likely to be mediated by the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK pathways.

Nanomaterials Facilitating Microbial Extracellular Electron Transfer at Interfaces.

Electrochemically active bacteria can transport their metabolically generated electrons to anodes, or accept electrons from cathodes to synthesize high-value chemicals and fuels, via a process known as extracellular electron transfer (EET). Harnessing of this microbial EET process has led to the development of microbial bio-electrochemical systems (BESs), which can achieve the interconversion of electrical and chemical energy and enable electricity generation, hydrogen production, electrosynthesis, wastewater treatment, desalination, water and soil remediation, and sensing. Here, the focus is on the current understanding of the microbial EET process occurring at both the bacteria-electrode interface and the biotic interface, as well as some attempts to improve the EET by using various nanomaterials. The behavior of nanomaterials in different EET routes and their influence on the performance of BESs are described. The inherent mechanisms will guide rational design of EET-related materials and lead to a better understanding of EET mechanisms.

Salvianic acid A alleviates chronic alcoholic liver disease by inhibiting HMGB1 translocation via down-regulating BRD4.

Alcoholic liver disease (ALD) is the major cause of chronic liver disease and a global health concern. ALD pathogenesis is initiated with liver steatosis, and ALD can progress to steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Salvianic acid A (SAA) is a phenolic acid component of Danshen, a Chinese herbal medicine with possible hepatoprotective properties. The purpose of this study was to investigate the effect of SAA on chronic alcoholic liver injury and its molecular mechanism. We found that SAA significantly inhibited alcohol-induced liver injury and ameliorated ethanol-induced hepatic inflammation. These protective effects of SAA were likely carried out through its suppression of the BRD4/HMGB1 signalling pathway, because SAA treatment largely diminished alcohol-induced BRD4 expression and HMGB1 nuclear translocation and release. Importantly, BRD4 knockdown prevented ethanol-induced HMGB1 release and inflammatory cytokine production in AML-12 cells. Similarly, alcohol-induced pro-inflammatory cytokines were blocked by HMGB1 siRNA. Collectively, our results reveal that activation of the BRD4/HMGB1 pathway is involved in ALD pathogenesis. Therefore, manipulation of the BRD4/HMGB1 pathway through strategies such as SAA treatment holds great therapeutic potential for chronic alcoholic liver disease therapy.

Sirtuin 3-mediated deacetylation of acyl-CoA synthetase family member 3 by protocatechuic acid attenuates non-alcoholic fatty liver disease.

BACKGROUND AND PURPOSE: Hepatic fatty acid metabolism disorder, a key pathogenic mechanism underlying non-alcoholic fatty liver disease (NAFLD), is associated with the hyperacetylation of mitochondrial enzymes. Acyl-CoA synthetase family member 3 (ACSF3), which is involved in the regulation of fatty acid metabolism, was predicted to contain lysine acetylation sites related to the mitochondrial deacetylase sirtuin 3 (SIRT3). The purpose of this study was to explore the underlying mechanism by which SIRT3 deacetylates ACSF3 in NAFLD and the protective effect of the natural phenolic compound protocatechuic acid (PCA) against fatty acid metabolism disorder via the SIRT3/ACSF3 pathway. EXPERIMENTAL APPROACH: The role of protocatechuic acid and its molecular mechanism in NAFLD were detected in rats and SIRT3-knockout mice fed a high-fat diet (HFD) and in AML-12 cells treated with palmitic acid (PA). KEY RESULTS: Pharmacological treatment with protocatechuic acid significantly attenuated high-fat diet-induced fatty acid metabolism disorder in NAFLD. Molecular docking assays showed that protocatechuic acid specifically bound SIRT3 as a substrate and increased SIRT3 protein expression. However, the protective role of protocatechuic acid was abolished by SIRT3 knockdown, which increased ACSF3 expression and exacerbated fatty acid metabolism disorder. Mechanistically, SIRT3 was shown to specifically regulate the acetylation and degradation of ACSF3, which govern the capacity of ACSF3 to mediate fatty acid metabolism disorder during NAFLD. CONCLUSION AND IMPLICATIONS: SIRT3-mediated ACSF3 deacetylation is a novel molecular mechanism in NAFLD therapy and protocatechuic acid confers protection against high-fat diet- and palmitic acid-induced hepatic fatty acid metabolism disorder through the SIRT3/ACSF3 pathway.

Protocatechuic Acid-Mediated miR-219a-5p Activation Inhibits the p66shc Oxidant Pathway to Alleviate Alcoholic Liver Injury.

Alcohol abuse has become common worldwide and has been recognized as a major cause of chronic alcoholic liver disease (ALD). ALD encompasses a complex process that includes a broad scope of hepatic lesions, ranging from steatosis to cirrhosis. In particular, reactive oxygen species (ROS) are mainly involved. Numerous studies have shown that p66shc plays a significant role in ALD. Protocatechuic acid (PCA), a dihydroxybenzoic acid that is naturally found in green tea, vegetables, and fruits, has efficient free radical scavenging effects. In this study, we aimed to assess the protective effect of PCA on ALD and to evaluate the microRNA- (miRNA-) p66shc-mediated reduction of ROS formation in ALD. Our results demonstrated that PCA treatment significantly decreased p66shc expression and downstream ROS formation in ALD. miR-219a-5p, which was identified by bioinformatics and experimental analysis, was enhanced by PCA and subsequently suppressed p66shc expression. Importantly, p66shc played an essential role in the protection of PCA-stimulated miR-219a-5p overexpression. Overall, these findings show that PCA-stimulated miR-219a-5p expression mitigates ALD by reducing p66shc-mediated ROS formation. This study may contribute to the development of therapeutic interventions for ALD.

Three-dimensional high performance free-standing anode by one-step carbonization of pinecone in microbial fuel cells.

In this paper, the free-standing macroporous carbon anode is prepared by one-step carbonization of pinecone without any further modification. The obtained anode is N, P-codoped porous carbon material, which is beneficial for electrochemical active bacterial adhesion and the fast start-up of cells. Both of the output voltage and long-term operation stability of the obtained anode are higher than that of carbon felt. The charge transfer resistance after biofilm formation is only 1.4 Ω, being 85.1% lower than that of carbon felt anode. 16S rRNA gene sequence analysis shows that Geobacter soli is the main electricigen and its ratio at the obtained anode is much higher than that at carbon felt (77.4% vs 34.0%). The N, P-codoped carbon as the three-dimensional free-standing anode has excellent electrochemical properties and is low cost and easy preparation. Most importantly, it enhances extracellular electron transfer, thus has potential application in microbial fuel cells.

Salvianolic Acid A Attenuates Endoplasmic Reticulum Stress and Protects Against Cholestasis-Induced Liver Fibrosis via the SIRT1/HSF1 Pathway.

Background: Endoplasmic reticulum stress (ER stress) plays a critical role in the pathogenesis of liver fibrosis; thus, it can be a potential therapeutic target of fibrosis. However, the mechanism of ER stress regulation in fibrosis, particularly through sirtuin 1 (SIRT1), remains unclear. The objective of this study was to investigate the effect of SIRT1-mediated inhibition of ER stress in bile duct ligation (BDL)-induced liver fibrosis, and to explore the effect of salvianolic acid A (SalA) on BDL-induced liver fibrosis through SIRT1/heat shock factor 1 (HSF1) signaling. Materials and Methods: We explored the effects of SalA on liver fibrosis and ER stress in BDL-induced liver fibrosis in rats and the human hepatic stellate cell line LX2 cells. The LX2 cells were treated with 20 ng of platelet-derived growth factor-BB homodimer (PDGF-BB) for 24 h, and then incubated in the absence or presence of SalA (25 µM) for 24 h. Results: In vivo, SalA treatment alleviated BDL-induced liver injury and ER stress. Importantly, SalA treatment increased HSF1 expression and activity using a SIRT1-dependent mechanism. In LX2 cells, PDGF-BB induced ER stress and fibrosis were blocked by HSF1 overexpression. Furthermore, SIRT1 siRNA abrogated the SalA-mediated promotion of HSF1 deacetylation and expression, suggesting that SalA-mediated protection occurs by SIRT1 targeting HSF1 for deacetylation. Conclusion: This is the first study to identify the SIRT1/HSF1 pathway as a key therapeutic target for controlling BDL-induced liver fibrosis and to show that SalA confers protection against BDL- and PDGF-BB-induced hepatic fibrosis and ER stress through SIRT1-mediated HSF1 deacetylation.

FeS2 Nanoparticles Decorated Graphene as Microbial-Fuel-Cell Anode Achieving High Power Density.

Microbial fuel cells (MFCs) have received great attention worldwide due to their potential in recovering electrical energy from waste and inexhaustible biomass. Unfortunately, the difficulty of achieving the high power, especially in real samples, remains a bottleneck for their practical applications. Herein, FeS2 nanoparticles decorated graphene is fabricated via a simple hydrothermal reaction. The FeS2 nanoparticles decorated graphene anode not only benefits bacterial adhesion and enrichment of electrochemically active Geobacter species on the electrode surface but also promotes efficient extracellular electron transfer, thus giving rise to a fast start-up time of 2 d, an unprecedented power density of 3220 mW m-2 and a remarkable current density of 3.06 A m-2 in the acetate-feeding and mixed bacteria-based MFCs. Most importantly, the FeS2 nanoparticles decorated graphene anode successfully achieves a power density of 310 mW m-2 with simultaneous removal of 1319 ± 28 mg L-1 chemical oxygen demand in effluents from a beer factory wastewater. The characteristics of improved power generation and enhanced pollutant removal efficiency opens the door toward development of high-performance MFCs via rational anode design for practical application.