Nicotinamide N-Methyltransferase (NNMT) is Involved in Gastric Adenocarcinoma Immune Infiltration by Driving Amino Acid Metabolism.

Objectives: This study investigates the role of Nicotinamide N-methyltransferase (NNMT) in immune infiltration modulation through amino acid metabolism in gastric adenocarcinoma (STAD). Methods: Utilizing data from The Cancer Genome Atlas (TCGA) and validated with clinical samples, we analyzed NNMT expression and its prognostic implications in STAD. Differential amino acid profiles between cancerous and adjacent normal tissues were assessed, along with their associations with NNMT. Results: NNMT exhibits heightened expression in STAD cancer tissues, positively correlating with tumor immune infiltration. Additionally, twenty-eight amino acids display differential expression in gastric tissue, with their metabolic enzymes showing connections to NNMT. Conclusions: Elevated NNMT expression in STAD tissues potentially influences amino acid metabolism, thereby affecting immune infiltration dynamics and tumorigenesis in gastric adenocarcinoma.

Synergistic suppression of BDNF via epigenetic mechanism deteriorating learning and memory impairment caused by Mn and Pb co-exposure.

Microglia, the resident immune cells of the central nervous system (CNS), play a dual role in neurotoxicity by releasing the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF) in response to environmental stress. Suppression of BDNF is implicated in learning and memory impairment induced by exposure to manganese (Mn) or lead (Pb) individually. Methyl CpG Binding Protein 2 (MeCp2) and its phosphorylation status are related to BDNF suppression. Protein phosphatase2A (PP2A), a member of the serine/threonine phosphatases family, dephosphorylates substrates based on the methylation state of its catalytic C subunit (PP2Ac). However, the specific impairment patterns and molecular mechanisms resulting from co-exposure to Mn and Pb remain unclear. Therefore, the purpose of this study was to explore the effects of Mn and Pb exposure, alone and in combination, on inducing neurotoxicity in the hippocampus of mice and BV2 cells, and to determine whether simultaneous exposure to both metals exacerbate their toxicity. Our findings reveal that co-exposure to Mn and Pb leads to severe learning and memory impairment in mice, which correlates with the accumulation of metals in the hippocampus and synergistic suppression of BDNF. This suppression is accompanied by up-regulation of the epigenetic repressor MeCp2 and its phosphorylation status, as well as demethylation of PP2Ac. Furthermore, inhibition of PP2Ac demethylation using ABL127, an inhibitor for its protein phosphatase methylesterase1 (PME1), or knockdown of MeCp2 via siRNA transfection in vitro effectively increases BDNF expression and mitigates BV2 cell damage induced by Mn and Pb co-exposure. We also observe abnormal activation of microglia characterized by enhanced release of the NLRP3 inflammasome, Casepase-1 and pro-inflammatory cytokines IL-1ß, in the hippocampus of mice and BV2 cells. In summary, our experiments demonstrate that simultaneous exposure to Mn and Pb results in more severe hippocampus-dependent learning and memory impairment, which is attributed to epigenetic suppression of BDNF mediated by PP2A regulation.

A qualitative study of food sociality in three provinces of South China: social functions of food and dietary behavior.

Background: Food sociality refers to the exploration of food production, exchange, distribution, and consumption and influences on cultural communication and social meaning. This study aimed to investigate food sociality in three provinces of South China to provide theoretical and practical evidence of food sociality in the region and to revise nutrition policies. Materials and methods: We conducted a qualitative study comprising 25 experts in the fields of nutrition, sociology, food science, and agriculture from Hainan, Guangdong, and Guangxi Province by using a semi-structured in-depth interview, which included 28 pre-determined questions covering six topics. The interviews were conducted between November 2020 and March 2021. Verbatim transcripts were analyzed thematically using NVivo 11.0. Results: Of the 25 experts, the mean age was 50.6 (SD = 8.4) years, 15 (60%) were male, and 22 (88%) held a master's degree or above. The analysis showed that food sociality in three provinces of South China mainly comprises social functions of food and dietary behavior. Regarding social functions of food, the experts expressed that food represents local culture (72%, 18 experts), presents social status and economic power (40%, 10 experts), and is central to special occasions, traditional customs, and etiquette activities (60%, 15 experts). In terms of social functions of dietary behaviors, the majority of experts indicated that food is a social communication tool (72% experts), has geographical characteristics (80% experts), and, to some extent, is used as a proxy for reward or punishment. Furthermore, festivals are one of the core elements of food sociality in the region, although food safety is a major concern. Some dietary behaviors, such as overindulgence in afternoon tea and encouraging drinking, may increase the risk of chronic diseases. Conclusion: Food sociality in three provinces of South China is mainly related to the social function of food and dietary behavior. It is a combination of local culture, social status and economic power, traditional customs, rewards and punishments, geographical food preference, and social communication tools. The authors recommend increasing food safety at festivals and promoting healthy eating behaviors in order to improve the overall health of the population in this region.

PdCu nanoalloy decorated photocatalysts for efficient and selective oxidative coupling of methane in flow reactors.

Methane activation by photocatalysis is one of the promising sustainable technologies for chemical synthesis. However, the current efficiency and stability of the process are moderate. Herein, a PdCu nanoalloy (~2.3 nm) was decorated on TiO2, which works for the efficient, stable, and selective photocatalytic oxidative coupling of methane at room temperature. A high methane conversion rate of 2480 µmol g-1 h-1 to C2 with an apparent quantum efficiency of ~8.4% has been achieved. More importantly, the photocatalyst exhibits the turnover frequency and turnover number of 116 h-1 and 12,642 with respect to PdCu, representing a record among all the photocatalytic processes (λ > 300 nm) operated at room temperature, together with a long stability of over 112 hours. The nanoalloy works as a hole acceptor, in which Pd softens and weakens C-H bond in methane and Cu decreases the adsorption energy of C2 products, leading to the high efficiency and long-time stability.

Low-dose benzo[a]pyrene exposure induces hepatic lipid deposition through LCMT1/PP2Ac-mediated autophagy inhibition.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disorder of liver metabolism and has become the most common chronic liver disease worldwide. Benzo[a]pyrene (BaP) is recognized as a potent carcinogen, but the effect of low-dose BaP on the development of NAFLD has not been well-studied, and its molecular mechanism is still unknown. In this study, we demonstrated that low-dose BaP induced hepatic steatosis in a mouse model with a notable increase in hepatic lipid content. Interestingly, mRNA expression of genes related to fatty acids uptake or synthesis was not significantly altered after BaP exposure. Instead, we found that low-dose BaP promoted lipid deposition in primary mouse hepatocytes by inhibiting autophagy, which was regulated through Leucine carboxyl methyltransferase-1 (LCMT1) mediated Protein Phosphatases 2A subunit C (PP2Ac) methylation. The role of LCMT1 in BaP-induced steatosis was further validated in a liver-specific lcmt1 knockout (L-LCMT1 KO) mouse model. In this study, we provided evidence to support a novel mechanism by which BaP induces the development of hepatic steatosis through PP2Ac mediated autophagy inhibition. These findings provided new insight into the pathogenesis of NAFLD induced by environmental exposure to low-dose BaP.

Highly selective oxidation of benzene to phenol with air at room temperature promoted by water.

Phenol is one of the most important fine chemical intermediates in the synthesis of plastics and drugs with a market size of ca. $30b1 and the commercial production is via a two-step selective oxidation of benzene, requiring high energy input (high temperature and high pressure) in the presence of a corrosive acidic medium, and causing serious environmental issues2-5. Here we present a four-phase interface strategy with well-designed Pd@Cu nanoarchitecture decorated TiO2 as a catalyst in a suspension system. The optimised catalyst leads to a turnover number of 16,000-100,000 for phenol generation with respect to the active sites and an excellent selectivity of ca. 93%. Such unprecedented results are attributed to the efficient activation of benzene by the atomically Cu coated Pd nanoarchitecture, enhanced charge separation, and an oxidant-lean environment. The rational design of catalyst and reaction system provides a green pathway for the selective conversion of symmetric organic molecules.

Effective Activation of Strong C-Cl Bonds for Highly Selective Photosynthesis of Bibenzyl via Homo-Coupling.

Carbon-carbon (C-C) coupling of organic halides has been successfully achieved in homogeneous catalysis, while the limitation, e.g., the dependence on rare noble metals, complexity of the metal-ligand catalylst and the poor catalyst stability and recyclability, needs to be tackled for a green process. The past few years have witnessed heterogeneous photocatalysis as a green and novel method for organic synthesis processes. However, the study on C-C coupling of chloride substrates is rare due to the extremely high bond energy of C-Cl bond (327 kJ mol-1 ). Here, we report a robust heterogeneous photocatalyst (Cu/ZnO) to drive the homo-coupling of benzyl chloride with high efficiency, which achieves an unprecedented high selectivity of bibenzyl (93 %) and yield rate of 92 % at room temperature. Moreover, this photocatalytic process has been validated for C-C coupling of 10 benzylic chlorides all with high yields. In addition, the excellent stability has been observed for 8 cycles of reactions. With detailed characterization and DFT calculation, the high selectivity is attributed to the enhanced adsorption of reactants, stabilization of intermediates (benzyl radicals) for the selective coupling by the Cu loading and the moderate oxidation ability of the ZnO support, besides the promoted charge separation and transfer by Cu species.

[Taurine inhibits M2 polarization of macrophages by promoting mitophagy].

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.

High quantum efficiency of hydrogen production from methanol aqueous solution with PtCu-TiO2 photocatalysts.

Methanol with 12.5 wt% H2 content is widely considered a liquid hydrogen medium. Taking into account water with 11.1 wt% H2 content, H2 synthesis from the mixture of water and methanol is a promising method for on-demand hydrogen production. We demonstrate an atomic-level catalyst design strategy using the synergy between single atoms and nanodots for H2 production. The PtCu-TiO2 sandwich photocatalyst achieves a remarkable H2 formation rate (2,383.9 µmol h-1) with a high apparent quantum efficiency (99.2%). Furthermore, the oxidation product is a high-value chemical formaldehyde with 98.6% selectivity instead of CO2, leading to a nearly zero-carbon-emission process. Detailed investigations indicate a dual role of the copper atoms: an electron acceptor to facilitate photoelectron transfer to Pt, and a hole acceptor for the selective oxidation of methanol to formaldehyde, thus avoiding over-oxidation to CO2. The synergy between Pt nanodots and Cu single atoms together reduces the activation energy of this process to 13.2 kJ mol-1.

Hepatic leucine carboxyl methyltransferase 1 (LCMT1) contributes to high fat diet-induced glucose intolerance through regulation of glycogen metabolism.

Impaired glucose regulation is one of the most important risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which have become a major public health issue worldwide. Dysregulation of carbohydrate metabolism in liver has been shown to play a critical role in the development of glucose intolerance but the molecular mechanism has not yet been fully understood. In this study, we investigated the role of hepatic LCMT1 in the regulation of glucose homeostasis using a liver-specific LCMT1 knockout mouse model. The hepatocyte-specific deletion of LCMT1 significantly upregulated the hepatic glycogen synthesis and glycogen accumulation in liver. We found that the liver-specific knockout of LCMT1 improved high fat diet-induced glucose intolerance and insulin resistance. Consistently, the high fat diet-induced downregulation of glucokinase (GCK) and other important glycogen synthesis genes were reversed in LCMT1 knockout liver. In addition, the expression of GCK was significantly upregulated in MIHA cells treated with siRNA targeting LCMT1 and improved glycogen synthesis. In this study, we provided evidences to support the role of hepatic LCMT1 in the development of glucose intolerance induced by high fat diet and demonstrated that inhibiting LCMT1 could be a novel therapeutic strategy for the treatment of glucose metabolism disorders.

Synergy of Ag and AgBr in a Pressurized Flow Reactor for Selective Photocatalytic Oxidative Coupling of Methane.

Oxidation of methane into valuable chemicals, such as C2+ molecules, has been long sought after but the dilemma between high yield and high selectivity of desired products remains. Herein, methane is upgraded through the photocatalytic oxidative coupling of methane (OCM) over a ternary Ag-AgBr/TiO2 catalyst in a pressurized flow reactor. The ethane yield of 35.4 µmol/h with a high C2+ selectivity of 79% has been obtained under 6 bar pressure. These are much better than most of the previous benchmark performance in photocatalytic OCM processes. These results are attributed to the synergy between Ag and AgBr, where Ag serves as an electron acceptor and promotes the charge transfer and AgBr forms a heterostructure with TiO2 not only to facilitate charge separation but also to avoid the overoxidation process. This work thus demonstrates an efficient strategy for photocatalytic methane conversion by both the rational design of the catalyst for the high selectivity and reactor engineering for the high conversion.

LCMT1 indicates poor prognosis and is essential for cell proliferation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant type of cancers. Leuci carboxyl methyltransferase 1 (LCMT1) is a protein methyltransferase that plays an improtant regulatory role in both normal and cancer cells. The aim of this study is to evaluate the expression pattern and clinical significance of LCMT1 in HCC. METHODS: The expression pattern and clinical relevance of LCMT1 were determined using the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) program, and our datasets. Gain-of-function and loss-of-function studies were employed to investigate the cellular functions of LCMT1 in vitro and in vivo. Quantitative real-time polymerase chain reaction (RT-PCR) analysis, western blotting, enzymatic assay, and high-performance liquid chromatography were applied to reveal the underlying molecular functions of LCMT1. RESULTS: LCMT1 was upregulated in human HCC tissues, which correlated with a "poor" prognosis. The siRNA-mediated knockdown of LCMT1 inhibited glycolysis, promoted mitochondrial dysfunction, and increased intracellular pyruvate levels by upregulating the expression of alani-neglyoxylate and serine-pyruvate aminotransferase (AGXT). The overexpression of LCMT1 showed the opposite results. Silencing LCMT1 inhibited the proliferation of HCC cells in vitro and reduced the growth of tumor xenografts in mice. Mechanistically, the effect of LCMT1 on the proliferation of HCC cells was partially dependent on PP2A. CONCLUSIONS: Our data revealed a novel role of LCMT1 in the proliferation of HCC cells. In addition, we provided novel insights into the effects of glycolysis-related pathways on the LCMT1regulated progression of HCC, suggesting LCMT1 as a novel therapeutic target for HCC therapy.

Potential Role and Clinical Value of PPP2CA in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways. METHODS: Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC. RESULTS: Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expression Omnibus database and our in-house RNA-Seq database. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50-0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiver operator characteristic curve of 0.79 (95% CI: 0.75-0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PPP2CA may be involved in HCC were determined using miRWalk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks. CONCLUSIONS: PPP2CA is up-regulated in HCC and higher expression correlates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.

Regulation PP2Ac methylation ameliorating autophagy dysfunction caused by Mn is associated with mTORC1/ULK1 pathway.

Manganese (Mn) exposure leads to autophagy dysfunction and causes neurodegenerative diseases such as Parkinson's syndrome and Alzheimer's disease. However, the mechanism of neurotoxicity of Mn has been less clear. The methylation of the protein phosphatase 2A catalytic subunit determines the dephosphorylation activity of protein phosphatase and plays an important role in autophagy regulation. In this investigation, we established a model of Mn (0-2000 µmol/L) exposure to N2a cells for 12 h, used the PPME-1 inhibitor ABL-127, and constructed an LCMT1-overexpressing N2a cell line. We also regulated the PP2Ac methylation level and explored the effect of PP2Ac methylation on Mn-induced (0-1000 µmol/L) N2a cellular autophagy. Our results showed that Mn > 500 µmol/L induced N2a cell damage and increased oxidative stress. Moreover, Mn modulated autophagy in N2a cells by downregulating PP2Ac methylation, which regulated mTORC1 signaling pathway activation. Both ABL-127 and LCMT1 overexpression can upregulate PP2Ac methylation in parallel with ameliorating N2a cell abnormal autophagy induced by Mn, Briefly, the upregulation of PP2Ac methylation can ameliorate the autophagy disorder of N2a by Mn and effectively alleviate Mn-induced cytotoxicity and oxidative stress, indicating that regulation of autophagy is a protective strategy against Mn-induced neurotoxicity.

Combined exposure to multiple metals and cognitive function in older adults.

Single toxic metal exposure has been reported to be associated with impaired cognitive function, but less is known about the effects of combined exposure to multiple metals. The aim of the study was to investigate the potential associations and interactions of multiple metals with cognitive function in older adults using multi-pollutants approach. A cross-sectional study was conducted in a total of 2879 participants aged ≥ 60 years old. We systematically measured levels of 22 blood metals and used the Mini-Mental State Examination (MMSE) to assess the cognitive function. The least absolute shrinkage and selection operator (LASSO) penalized regression was applied to identify independently main metals. Adjusted estimates of cognitive function with selected metals were investigated by generalized linear regression in the multi-metal model. We found that calcium, titanium, vanadium, copper, zinc, arsenic, selenium, rubidium, molybdenum, cadmium, barium, and lead were independently identified based on LASSO penalized regression. The multi-metal model showed a higher MMSE of 0.384 (95% CI: 0.122-0.646) for a 1-SD increment in log-transformed rubidium and a lower MMSE of 0.460 (95% CI: - 0.706 to - 0.214) for a 1-SD increment in log-transformed cadmium (P < 0.05). The significantly negative associations between cadmium and cognitive function were attenuated to null accompanying with increasing concentrations of rubidium (P interaction = 0.256). Our findings suggested that blood rubidium and cadmium were mainly associated with cognitive function when accounting for co-exposure to other metals and higher level of rubidium appeared to attenuate the toxic effects of cadmium on cognitive function in older adults.

In Situ Investigation of Charge Performance in Anatase TiO2 Powder for Methane Conversion by Vis-NIR Spectroscopy.

The intrinsic behavior of photogenerated charges and reactions with chemicals are key for a photocatalytic process. To observe these basic steps is of great importance. Here we present a reliable and robust system to monitor these basic steps in powder photocatalysts, and more importantly to elucidate the key issue in photocatalytic methane conversion over the benchmark catalyst TiO2. Under constant excitation, the absorption signal across the NIR region was demonstrated to be dominated by photoexcited electrons, the absorption of photoexcited holes increases toward shorter wavelengths in the visible region, and the overall shapes of the photoinduced absorption spectra obtained using the system demonstrated in the present work are consistent with widely accepted transient absorption results. Next, in situ measurements provide direct experimental evidence that the initial step of methane activation over TiO2 involves oxidation by photoexcited holes. It is calculated that 90 ± 6% of photoexcited electrons are scavenged by O2 (in dry air), 61 ± 9% of photoexcited holes are scavenged by methane (10% in argon), and a similar amount of photoexcited electrons can be scavenged by O2 even when the O2 concentration is reduced by a factor of 10. The present results suggest that O2 is much more easily activated in comparison to methane over anatase TiO2, which rationalizes the much higher methane/O2 ratio frequently used in practice in comparison to that required stoichiometrically for photocatalytic production of value-added chemicals via methane oxidation with oxygen. In addition, methanol (a preferable product of methane oxidation) is much more readily oxidized than methane over anatase TiO2.

Taurine Antagonizes Macrophages M1 Polarization by Mitophagy-Glycolysis Switch Blockage via Dragging SAM-PP2Ac Transmethylation.

The excessive M1 polarization of macrophages drives the occurrence and development of inflammatory diseases. The reprogramming of macrophages from M1 to M2 can be achieved by targeting metabolic events. Taurine promotes for the balance of energy metabolism and the repair of inflammatory injury, preventing chronic diseases and complications. However, little is known about the mechanisms underlying the action of taurine modulating the macrophage polarization phenotype. In this study, we constructed a low-dose LPS/IFN-γ-induced M1 polarization model to simulate a low-grade pro-inflammatory process. Our results indicate that the taurine transporter TauT/SlC6A6 is upregulated at the transcriptional level during M1 macrophage polarization. The nutrient uptake signal on the membrane supports the high abundance of taurine in macrophages after taurine supplementation, which weakens the status of methionine metabolism, resulting in insufficient S-adenosylmethionine (SAM). The low availability of SAM is directly sensed by LCMT-1 and PME-1, hindering PP2Ac methylation. PP2Ac methylation was found to be necessary for M1 polarization, including the positive regulation of VDAC1 and PINK1. Furthermore, its activation was found to promote the elimination of mitochondria by macrophages via the mitophagy pathway for metabolic adaptation. Mechanistically, taurine inhibits SAM-dependent PP2Ac methylation to block PINK1-mediated mitophagy flux, thereby maintaining a high mitochondrial density, which ultimately hinders the conversion of energy metabolism to glycolysis required for M1. Our findings reveal a novel mechanism of taurine-coupled M1 macrophage energy metabolism, providing novel insights into the occurrence and prevention of low-grade inflammation, and propose that the sensing of taurine and SAM availability may allow communication to inflammatory response in macrophages.

The effect of micro-nutrients on malnutrition, immunity and therapeutic effect in patients with pulmonary tuberculosis: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Micro-nutrients are closely related to pulmonary tuberculosis (PTB). Most patients with PTB suffer from micro-nutrients deficiency. We aimed to evaluate the efficacy of micro-nutrients support on clinical therapy and chronic inflammation in patients with PTB. METHODS: We searched Pubmed, Springer link, Web of Science, Cochrane, Wan Fang and CNKI databases for randomised controlled trials (RCTs). The patients with anti-TB treatments were divided into two groups, the control group with nutritional advice or placebo, and the experimental group with micro-nutrients support for more than 2 weeks. Two reviewers conducted data extraction and quality assessment of the studies independently, and ReviewManager 5.2 software was used to input and analyse the data. The dichotomous variable was expressed in the risk ratios (RRS) and 95% CI, the continuous data were expressed in the mean difference (MD) and 95% CI, and the heterogeneity of subgroup was evaluated by I (Kerantzas and Jacobs, Jr., 2017) [2] test. RESULTS: A total of 13 trials (2847 participants) were included. First, micro-nutrients improved sputum smears or culture negative conversion rates (OR 0.16 0.03-0.77, 2.29; MD -2.36, -4.72~-0.01, z = 1.97). Meanwhile, micro-nutrients support increased lymphocytes and decreased leukocytes, neutrophils, CRP and ESR (MD 0.20, 0.06-0.35, z = 2.78; MD -0.42, -0.65~-0.18, z = 3.48; MD -0.66, -1.12~-0.20, z = 2.82). However it had not impact on body weight, MUAC, haemoglobin, albumin or monocytes (p > 0.05). CONCLUSION: Micro-nutrients support can reduce chronic inflammation and improve sputum smears or culture conversions to contribute to anti-TB treatment.

Methionine-Mediated Protein Phosphatase 2A Catalytic Subunit (PP2Ac) Methylation Ameliorates the Tauopathy Induced by Manganese in Cell and Animal Models.

The molecular mechanism of Alzheimer-like cognitive impairment induced by manganese (Mn) exposure has not yet been fully clarified, and there are currently no effective interventions to treat neurodegenerative lesions related to manganism. Protein phosphatase 2 A (PP2A) is a major tau phosphatase and was recently identified as a potential therapeutic target molecule for neurodegenerative diseases; its activity is directed by the methylation status of the catalytic C subunit. Methionine is an essential amino acid, and its downstream metabolite S-adenosylmethionine (SAM) participates in transmethylation pathways as a methyl donor. In this study, the neurotoxic mechanism of Mn and the protective effect of methionine were evaluated in Mn-exposed cell and rat models. We show that Mn-induced neurotoxicity is characterized by PP2Ac demethylation accompanied by abnormally decreased LCMT-1 and increased PME-1, which are associated with tau hyperphosphorylation and spatial learning and memory deficits, and that the poor availability of SAM in the hippocampus is likely to determine the loss of PP2Ac methylation. Importantly, maintenance of local SAM levels through continuous supplementation with exogenous methionine, or through specific inhibition of PP2Ac demethylation by ABL127 administration in vitro, can effectively prevent tau hyperphosphorylation to reduce cellular oxidative stress, apoptosis, damage to cell viability, and rat memory deficits in cell or animal Mn exposure models. In conclusion, our data suggest that SAM and PP2Ac methylation may be novel targets for the treatment of Mn poisoning and neurotoxic mechanism-related tauopathies.

Platinum- and CuOx -Decorated TiO2 Photocatalyst for Oxidative Coupling of Methane to C2 Hydrocarbons in a Flow Reactor.

Oxidative coupling of methane (OCM) is considered one of the most promising catalytic technologies to upgrade methane. However, C2 products (C2 H6 /C2 H4 ) from conventional methane conversion have not been produced commercially owing to competition from overoxidation and carbon accumulation at high temperatures. Herein, we report the codeposition of Pt nanoparticles and CuOx clusters on TiO2 (PC-50) and use of the resulting photocatalyst for OCM in a flow reactor operated at room temperature under atmospheric pressure for the first time. The optimized Cu0.1 Pt0.5 /PC-50 sample showed a highest yield of C2 product of 6.8 µmol h-1 at a space velocity of 2400 h-1 , more than twice the sum of the activity of Pt/PC-50 (1.07 µmol h-1 ) and Cu/PC-50 (1.9 µmol h-1 ), it might also be the highest among photocatalytic methane conversions reported so far under atmospheric pressure. A high C2 selectivity of 60 % is also comparable to that attainable by conventional high-temperature (>943 K) thermal catalysis. It is proposed that Pt functions as an electron acceptor to facilitate charge separation, while holes could transfer to CuOx to avoid deep dehydrogenation and the overoxidation of C2 products.