Pretreatment of wastepaper with an aqueous solution of amino acid-derived ionic liquid for biochar production as adsorbent.

The carbonization of lignocellulosic biomass with ionic liquids (ILs) are considered as an advantageous approach for the preparation of carbonaceous materials. The commonly used imidazolium and pyridinium based ILs have drawbacks such as toxicity, resistance to biodegradation, high cost and viscosity. These issues can be mitigated by diluting ILs with water, although excessive water content above 1 wt% can reduce the solubility of biomass. This research aims to investigate the potential of pretreating wastepaper with a "fully green" ILs, amino acid-based IL with high water content, followed by pyrolysis without IL, in enhancing the properties of biochar. For this purpose, the paper was treated with an aqueous solution of IL cysteine nitrate ([Cys][NO3]), and the IL was not involved in the pyrolysis process to prevent the formation of secondary gaseous pollutants. The findings revealed that the hemicellulose and mineral filler in the paper were eliminated during pretreatment, leading to higher carbon content but lower oxygen content. As a result, the biochar exhibited micropores of 0.42 cm3g-1 and a specific surface area of 1011.21 m2 g-1. The biochar demonstrated high adsorption capacities for Cd2+, enrofloxacin, bisphenol A, ciprofloxacin, and tetracycline, with values of 45.20 mg g-1, 49.82 mg g-1, 49.90 mg g-1, 49.88 mg g-1, and 49.65 mg g-1, respectively. The proposed mechanism for the adsorption of enrofloxacin by the biochar primarily involves physical adsorption such as pore filling and electrostatic interactions, along with chemical adsorption facilitated by graphitic nitrogen.

Type VII secretion system extracellular protein B targets STING to evade host anti-Staphylococcus aureus immunity.

Staphylococcus aureus (S. aureus) can evade antibiotics and host immune defenses by persisting within infected cells. Here, we demonstrate that in infected host cells, S. aureus type VII secretion system (T7SS) extracellular protein B (EsxB) interacts with the stimulator of interferon genes (STING) protein and suppresses the inflammatory defense mechanism of macrophages during early infection. The binding of EsxB with STING disrupts the K48-linked ubiquitination of EsxB at lysine 33, thereby preventing EsxB degradation. Furthermore, EsxB-STING binding appears to interrupt the interaction of 2 vital regulatory proteins with STING: aspartate-histidine-histidine-cysteine domain-containing protein 3 (DHHC3) and TNF receptor-associated factor 6. This persistent dual suppression of STING interactions deregulates intracellular proinflammatory pathways in macrophages, inhibiting STING's palmitoylation at cysteine 91 and its K63-linked ubiquitination at lysine 83. These findings uncover an immune-evasion mechanism by S. aureus T7SS during intracellular macrophage infection, which has implications for developing effective immunomodulators to combat S. aureus infections.

Toxins from harmful algal blooms: How copper and iron render chalkophore a predictor of microcystin production.

Research on harmful algal blooms has focused on macronutrients, yet recent research increasingly indicates that understanding micronutrient roles is also important in the development of effective environmental management interventions. Here, we report results on metallophore production from mesocosms amended with copper and iron (enzymatic co-factors in photosynthetic electron transport) to probe questions of how cyanobacteria navigate the divide between copper nutrition, copper toxicity, and issues with iron bioavailability. These experiments utilized Microcystis, Chlorella and Desmodesmus spp., in mono- and mixed-cultures in lake water from a large, hypereutrophic lake (Taihu, China). To initiate experiments, copper and iron amendments were added to mesocosms containing algae that had been acclimated to achieve a state of copper and iron limitation. Mesocosms were analyzed over time for a range of analytes including algal growth parameters, algal assemblage progression, copper/iron concentrations and biomolecule production of chalkophore, siderophore and total microcystins. Community Trajectory Analysis and other multivariate methods were used for analysis resulting in our findings: 1) Microcystis spp. manage copper/iron requirements though a dynamically phased behavior of chalkophore/siderophore production according to their copper and iron limitation status (chalkophore correlates with Cu concentration, R2 = 0.99, and siderophore correlates with the sum of Cu and Fe concentrations, R2 = 0.98). 2) A strong correlation was observed between the production of chalkophore and the cyanobacterial toxin microcystin (R2 = 0.76)-Chalkophore is a predictor of microcystin production. 3) Based on our results and literature, we posit that Microcystis spp. produces microcystin in response to copper/iron availability to manage photosystem productivity and effect an energy-saving status. Results from this work underscore the importance of micronutrients in influencing harmful algal bloom progression and represents a major advance in understanding the ecological function for the cyanobacterial toxin microcystin as a hallmark of micronutrient limitation stress.

Enhancement of anaerobic digestion of rice straw by amino acid-derived ionic liquid.

This study proposes a novel method to enhance methane production from anaerobic digestion using an amino acid-derived ionic liquid, glycine hydrochloride, ([Gly][Cl]), as an exogenous additive. After 40 days of digestion with 5% [Gly][Cl], the cumulative methane production was 115.56 mL/g VS, which was 73% higher than that of the control group (without additive). Specifically, the peak activities of cellulase, xylanase, and lignin peroxidase were significantly higher than those of the control group. The addition of [Gly][Cl] increased bacterial diversity and reduced archaeal diversity. Synergistota represented by Syner-01, Fibrobacterota represented by BBMC-4, Bacteroides, and unclassified_f__Lachnospiraceae significantly increased in relative abundance. It suggested that [Gly][Cl] stimulated the activities of protein-hydrolyzing and acid-producing bacteria. [Gly][Cl] also increased the abundance of methanogens and archaea, converting more lignocellulose to methane. Methanobacterium, that metabolizes H2 and CO2 to CH4, was more abundant. Therefore, [Gly][Cl] can improve methane yield as an anaerobic digestion additive.

Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1highCD11b+ cells elimination in hepatocellular carcinoma.

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1highCD11b+ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8+ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1highCD11b+ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1highCD11b+ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

TREM2+ macrophages suppress CD8+ T-cell infiltration after transarterial chemoembolisation in hepatocellular carcinoma.

BACKGROUND & AIMS: The immune landscape of hepatocellular carcinoma (HCC) following transarterial chemoembolisation (TACE) remains to be clarified. This study aimed to characterise the immune landscape following TACE and the underlying mechanism of HCC progression. METHODS: Tumour samples from five patients with treatment-naive HCC and five patients who received TACE therapy were collected and subjected to single-cell RNA sequencing. Another 22 paired samples were validated using immunofluorescence staining and flow cytometry. To clarify the underlying mechanisms, in vitro co-culture experiments and two types of TREM2-KO/WT mouse models, namely, an HCC cell orthotopic injection model and a spontaneous HCC model, were used. RESULTS: A reduced number of CD8+ T cells and an increased number of tumour-associated macrophages (TAMs) were observed in the post-TACE microenvironment. TACE therapy reduced the cluster CD8_C4, which was highly enriched with tumour-specific CD8+ T cells of pre-exhausted phenotype. TREM2 was found to be highly expressed in TAMs following TACE, which was associated with a poor prognosis. TREM2+ TAMs secreted less CXCL9 but more galectin-1 than did TREM2- TAMs. Galectin-1 promoted PD-L1 overexpression in vessel endothelial cells, impeding CD8+ T cell recruitment. TREM2 deficiency also increased CD8+ T cell infiltration, which inhibited tumour growth in both in vivo HCC models. More importantly, TREM2 deficiency enhanced the therapeutic effect of anti-PD-L1 blockade. CONCLUSIONS: This study shows that TREM2+ TAMs play an important role in suppressing CD8+ T cells. TREM2 deficiency increased the therapeutic effect of anti-PD-L1 blockade by enhancing antitumour activity of CD8+ T cells. These findings explain the reasons for recurrence and progression after TACE and provide a new target for HCC immunotherapy after TACE. IMPACT AND IMPLICATIONS: Studying the immune landscape in post-TACE HCC is important to uncover the mechanisms of HCC progression. By using scRNA sequencing and functional assays, we discovered that both the number and function of CD8+ T cells are compromised, whereas the number of TREM2+ TAMs is increased in post-TACE HCC, correlating with worse prognosis. Moreover, TREM2 deficiency dramatically increases CD8+ T cell infiltration and augments the therapeutic efficacy of anti-PD-L1 blockade. Mechanistically, TREM2+ TAMs display lower CXCL9 and increased Gal-1 secretion than do TREM2- TAMs, with Gal-1 mediating the overexpression of PD-L1 in vessel endothelial cells. These results suggest that TREM2 could be a novel immunotherapeutic target for patients treated with TACE in HCC. This provides an opportunity to break the plateau of limited therapeutic effect. This study has the value of understanding the tumour microenvironment of post-TACE HCC and thinking a new strategy of immunotherapy in the field of HCC. It is therefore of key impact for physicians, scientists and drug developers in the field of liver cancer and gastrointestinal oncology.

Analysis of oil synthesis pathway in Cyperus esculentus tubers and identification of oleosin and caleosin genes.

The tubers of the widely distributed Cyperus esculentus are rich in oil, and therefore, the plant is considered to have a high utilization value in the vegetable oil industry. Oleosins and caleosins are lipid-associated proteins found in oil bodies of seeds; however oleosins and caleosins genes have not been identified in C. esculentus. In this study, we performed transcriptome sequencing and lipid metabolome analysis of C. esculentus tubers at four developmental stages to obtain the information on their genetic profile, expression trends, and metabolites in oil accumulation pathways. Overall, 120,881 non-redundant unigenes and 255 lipids were detected; 18 genes belonged to the acetyl-CoA carboxylase (ACC), malonyl-CoA:ACP transacylase (MCAT), ß-ketoacyl-ACP synthase (KAS), and fatty acyl-ACP thioesterase (FAT) gene families involved in fatty acid biosynthesis, and 16 genes belonged to the glycerol-3-phosphate acyltransferase (GPAT), diacylglycerol acyltransferase 3 (DGAT3), phospholipid:diacylglycerol acyltransferase (PDAT), FAD2, and lysophosphatidic acid acyltransferase (LPAAT) gene families playing important roles in triacylglycerol synthesis. We also identified 9 oleosin- and 21 caleosin-encoding genes in C. esculentus tubers. These results provide detailed information on the C. esculentus transcriptional and metabolic profiles, which can be used as reference for the development of strategies to increase oil content in C. esculentus tubers.

Identification and Validation of Novel Immunogenic Cell Death- and DNA Damage Response-Related Molecular Patterns Correlated with Immune Status and Prognosis in Hepatocellular Carcinoma.

Immunogenic cell death (ICD) and DNA damage response (DDR) are involved in cancer progression and prognosis. Currently, chemotherapy is the first-line treatment for intermediate or advanced hepatocellular carcinoma (HCC), which is mostly based on platinum and anthracyclines that induce DNA damage and ICD. With the treatment of HCC with immune checkpoint inhibitors (ICIs), it is important to understand the molecular characteristics and prognostic values of ICD and DDR-related genes (IDRGs). We aimed to explore the characteristics of ICD and DDR-related molecular patterns, immune status, and the association of immunotherapy and prognosis with IDRGs in HCC. We identified IDRGs in HCC and evaluated their differential expression, biological behaviors, molecular characteristics, immune cell infiltration, and prognostic value. Prognostic IDRGs and subtypes were identified and validated. FFAR3, DDX1, POLR3G, FANCL, ADA, PI3KR1, DHX58, TPT1, MGMT, SLAMF6, and EIF2AK4 were determined as risk factors for HCC, and the biological experiments indicated that high FANCL expression is harmful to the treatment and prognosis. HCC was classified into high- and low-risk groups based on the median values of the risk factors to construct a predictive nomogram. These findings provide novel insights into the treatment and prognosis of HCC and provide a new research direction for HCC.

Corrigendum: OIT3 serves as a novel biomarker of hepatocellular carcinoma by mediating ferroptosis via regulating the arachidonic acid metabolism.

[This corrects the article DOI: 10.3389/fonc.2022.977348.].

Dissecting a hypoxia-related angiogenic gene signature for predicting prognosis and immune status in hepatocellular carcinoma.

Background: Hypoxia and angiogenesis, as prominent characteristics of malignant tumors, are implicated in the progression of hepatocellular carcinoma (HCC). However, the role of hypoxia in the angiogenesis of liver cancer is unclear. Therefore, we explored the regulatory mechanisms of hypoxia-related angiogenic genes (HRAGs) and the relationship between these genes and the prognosis of HCC. Methods: The transcriptomic and clinical data of HCC samples were downloaded from public datasets, followed by identification of hypoxia- and angiogenesis-related genes in the database. A gene signature model was constructed based on univariate and multivariate Cox regression analyses, and validated in independent cohorts. Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) curves were generated to evaluate the model's predictive capability. Gene set enrichment analysis (GSEA) was performed to explore signaling pathways regulated by the gene signature. Furthermore, the relationships among gene signature, immune status, and response to anti-angiogenesis agents and immune checkpoint blockade (ICB) were analyzed. Results: The prognostic model was based on three HRAGs (ANGPT2, SERPINE1 and SPP1). The model accurately predicted that low-risk patients would have longer overall survival than high-risk patients, consistent with findings in other cohorts. GSEA indicated that high-risk group membership was significantly associated with hypoxia, angiogenesis, the epithelial-mesenchymal transition, and activity in immune-related pathways. The high-risk group also had more immunosuppressive cells and higher expression of immune checkpoints such as PD-1 and PD-L1. Conversely, the low-risk group had a better response to anti-angiogenesis and ICB therapy. Conclusions: The gene signature based on HRAGs was predictive of prognosis and provided an immunological perspective that will facilitate the development of personalized therapies.

OIT3 serves as a novel biomarker of hepatocellular carcinoma by mediating ferroptosis via regulating the arachidonic acid metabolism.

Background: Oncoprotein-Induced Transcript 3 Protein (OIT3) was identified as a liver-specific gene with abnormal expression in hepatocellular carcinoma (HCC). Herein, we aimed to examine the function and specific mechanism of OIT3 in HCC. Methods: Bioinformatic analyses and tissue microarray via immunohistochemistry were used to validate the expression of OIT3 in HCC. The biofunctions of OIT3 in HCC were determined in vitro and in vivo. The mechanism was confirmed by RNA-Sequence and Western blotting. The uni- and multivariate analyses were used to identify the independent predictors for HCC. Results: Low expression of OIT3 was observed in HCC and predicted a poor clinical outcome. Ectopic expression of OIT3 could inhibit the proliferation, migration, and invasion abilities of HCC cells. Mechanistically, OIT3 upregulated the expression of ALOX15 and CYP4F3, thus inducing arachidonic acid increase, ROS accumulation, and lipid peroxidation, and eventually causing ferroptosis. OIT3 was validated as a prognostic predictor for HCC patients. Conclusions: Our findings revealed a novel role of OIT3 in the process of tumorigenesis of HCC. OIT3 inhibited reproliferation, migration, and invasion of HCC cells by triggering ferroptosis, which indicates that OIT3 could serve as a potential biomarker in HCC.

Extracellular fibrinogen-binding protein released by intracellular Staphylococcus aureus suppresses host immunity by targeting TRAF3.

Many pathogens secrete effectors to hijack intracellular signaling regulators in host immune cells to promote pathogenesis. However, the pathogenesis of Staphylococcus aureus secretory effectors within host cells is unclear. Here, we report that Staphylococcus aureus secretes extracellular fibrinogen-binding protein (Efb) into the cytoplasm of macrophages to suppress host immunity. Mechanistically, RING finger protein 114, a host E3 ligase, mediates K27-linked ubiquitination of Efb at lysine 71, which facilitates the recruitment of tumor necrosis factor receptor associated factor (TRAF) 3. The binding of Efb to TRAF3 disrupts the formation of the TRAF3/TRAF2/cIAP1 (cellular-inhibitor-of-apoptosis-1) complex, which mediates K48-ubiquitination of TRAF3 to promote degradation, resulting in suppression of the inflammatory signaling cascade. Additionally, the Efb K71R mutant loses the ability to inhibit inflammation and exhibits decreased pathogenicity. Therefore, our findings identify an unrecognized mechanism of Staphylococcus aureus to suppress host defense, which may be a promising target for developing effective anti-Staphylococcus aureus immunomodulators.

Kinetics of the Gas-Phase Reaction of Hydroxyl Radicals with Dimethyl Methylphosphonate (DMMP) over an Extended Temperature Range (273-837 K).

The kinetics of the reaction of hydroxyl radical (OH) with dimethyl methylphosphonate (DMMP, (CH3O)2CH3PO) (reaction 1) OH + DMMP → products (1) was studied at the bath gas (He) pressure of 1 bar over the 295-837 K temperature range. Hydroxyl radicals were produced in the fast reaction of electronically excited oxygen atoms O(1D) with H2O. The time-resolved kinetic profiles of hydroxyl radicals were recorded via UV absorption at around 308 nm using a DC discharge H2O/Ar lamp. The reaction rate constant exhibits a pronounced V-shaped temperature dependence, negative in the low temperature range, 295-530 K (the rate constant decreases with temperature), and positive in the elevated temperature range, 530-837 K (the rate constant increases with temperature), with a turning point at 530 ± 10 K. The rate constant could not be adequately fitted with a standard 3-parameter modified Arrhenius expression. The data were fitted with a 5-parameter expression as: k1 = 2.19 × 10-14(T/298)2.43exp(15.02 kJ mol-1/RT) + 1.71 × 10-10exp(-26.51 kJ mol-1/RT) cm3molecule-1s-1 (295-837 K). In addition, a theoretically predicted pressure dependence for such reactions was experimentally observed for the first time.

Pore-forming alpha-hemolysin efficiently improves the immunogenicity and protective efficacy of protein antigens.

Highly immunogenic exotoxins are used as carrier proteins because they efficiently improve the immunogenicity of polysaccharides. However, their efficiency with protein antigens remains unclear. In the current study, the candidate antigen PA0833 from Pseudomonas aeruginosa was fused to the α-hemolysin mutant HlaH35A from Staphylococcus aureus to form a HlaH35A-PA0833 fusion protein (HPF). Immunization with HPF resulted in increased PA0833-specific antibody titers, higher protective efficacy, and decreased bacterial burden and pro-inflammatory cytokine secretion compared with PA0833 immunization alone. Using fluorescently labeled antigens to track antigen uptake and delivery, we found that HlaH35A fusion significantly improved antigen uptake in injected muscles and antigen delivery to draining lymph nodes. Both in vivo and in vitro studies demonstrated that the increased antigen uptake after immunization with HPF was mainly due to monocyte- and macrophage-dependent macropinocytosis, which was probably the result of HPF binding to ADAM10, the Hla host receptor. Furthermore, a transcriptome analysis showed that several immune signaling pathways were activated by HPF, shedding light on the mechanism whereby HlaH35A fusion improves immunogenicity. Finally, the improvement in immunogenicity by HlaH35A fusion was also confirmed with two other antigens, GlnH from Klebsiella pneumoniae and the model antigen OVA, indicating that HlaH35A could serve as a universal carrier protein to improve the immunogenicity of protein antigens.

A new perspective of copper-iron effects on bloom-forming algae in a highly impacted environment.

Relatively little work has been done on the role of micronutrients in influencing development and progression of harmful algal blooms, yet micronutrients are ineluctably required for growth. Relatively small changes in micronutrient status have wide-ranging consequences. Here, we report results from mesocosm experiments with Microcystis and Desmodesmus spp., in mono- and mixed-cultures, to probe questions of how copper, iron, and copper-iron amendments affect growth, short-term assemblage progression, and production of siderophore, chalkophore, and microcystin in lake water from a large, hypereutrophic lake (Taihu, China). Our approach offers an entirely new perspective to understanding micronutrient dynamics in aqueous environments, as this is the first work to systematically screen for chalkophores and siderophores separately, as a function of copper/iron amendment, and using community trajectory analysis. Singular findings are summarized as follows: 1) unlike lab-based studies, in our work we observe neither dramatic copper-modulation of iron demand, nor evidence of an iron-protective effect from copper toxicity. 2) The interplay between chalkophore/siderophore production supports a concept model wherein Microcystis spp. varies behavior to individually and uniquely manage copper/iron requirements in a phased manner. In being able to specifically screen for chalkophores, we observe a previously unreported link between chalkophore and microcystin production that may relate to iron-limitation. 3) Regarding harmful algal bloom (HAB) persistance, the lake water itself influences mesocosm changes; differentiated effects for iron regarding growth indicators and/or reduction of Fe-limitation stress were found at an HAB-free field station (Xukou Bay), likely a consequence of low bioavailability of iron in this station as compared to HAB-impacted stations (half the initial dissolved iron concentration, persisting throughout experiments). The low dissolved iron accompanies more intense chalkophore/siderophore community trajectories.

Co-delivery of cisplatin and oleanolic acid by silica nanoparticles-enhanced apoptosis and reverse multidrug resistance in lung cancer.

Multidrug resistance (MDR) of chemotherapy is one of the significant concerns in cancer therapy. Here in our study, cisplatin (DDP) and oleanolic acid (OA) were co-loaded in mesoporous silica nanoparticles (Nsi) to construct DDP/OA-Nsi and solve the DDP-resistance in lung cancer therapy. The cytotoxicity and apoptosis assays demonstrated that in DDP-resistant A549/DDP cells, the cytotoxicity of DDP/OA-Nsi was significantly higher than that of free DDP or DDP single delivery system (DDP-Nsi). The intracellular drug accumulation study revealed that the intracellular DDP concentration in the DDP/OA-Nsi group was also higher than that in free DDP and DDP-Nsi groups. In the A549/DDP xenograft tumor model, DDP/OA-Nsi showed the best anticancer effect. In summary, DDP/OA-Nsi was a promising drug delivery system to solve MDR in lung cancer therapy.

lncRNA PVT1 promotes the migration of gastric cancer by functioning as ceRNA of miR-30a and regulating Snail.

Although the incidence and mortality of gastric cancer (GC) are slowly decreasing, the overall prognosis of GC patients with distal metastasis remains dismal. Long non-coding RNA PVT1 has been verified to function as a tumor promoter in several types of cancer. However, the role of PVT1 in GC metastasis remains obscure. Herein, we found that PVT1 was highly expressed in GC tissues and high PVT1 level was associated with tumor stage, lymph node metastasis, and poor prognosis. Overexpression of PVT1 significantly elevated epithelial-to-mesenchymal transition (EMT) marker (N-cadherin, ZEB1, and ZEB2) levels and promoted GC cell EMT process and tumor metastasis in vitro and in vivo. Mechanistically, Snail was identified as a direct target of miR-30a. PVT1 could bind with miR-30a and increase the expression of Snail by acting as a competing endogenous RNA, whereas re-expression of miR-30a in GC cells rescued the EMT markers, decreased Snail level, and inhibited GC cell migration. Taken together, these findings provide a new light on PVT1 in the pathogenesis and development of GC and an important implication for future therapy of the GC.

Origin and Spread of the ALDH2 Glu504Lys Allele.

Gene polymorphism of acetaldehyde dehydrogenase 2 (ALDH2), a key enzyme for alcohol metabolism in humans, can affect catalytic activity. The ALDH2 Glu504Lys mutant allele has a high-frequency distribution in East Asian populations and has been demonstrated to be associated with an increased risk of cardiovascular disease, stroke, and tumors. Available evidence suggests that the evolution of the ALDH2 gene has been influenced by multiple factors. Random mutations produce Glu504Lys, and genetic drift alters the frequency of this allele; additionally, environmental factors such as hepatitis B virus infection and high-elevation hypoxia affect its frequency through selective effects, ultimately resulting in a high frequency of this allele in East Asian populations. Here, the origin, selection, and spread of the ALDH2 Glu504Lys allele are discussed, and an outlook for further research is proposed to realize a precision medical strategy based on the genetic and environmental variations in ALDH2.

Kinetics of the gas-phase reaction of hydroxyl radicals with trimethyl phosphate over the 273-837 K temperature range.

The kinetics of the reaction of hydroxyl radical (OH) with trimethyl phosphate (CH3O)3PO (TMP) (reaction (1)) OH + TMP → products (1) was studied at the bath gas (He) pressure of 1 bar over the 273-837 K temperature range. Hydroxyl radicals were produced in fast reactions of electronically excited oxygen atoms O(1D) with either H2O or H2. Excited oxygen atoms O(1D) were produced by photolysis of ozone, O3, at 266 nm (4th harmonic of Nd:YAG laser) over the 273-470 K temperature range and by photolysis of N2O at 193 nm (ArF excimer laser) over the whole temperature range including the elevated temperature range 470-837 K. The reaction rate constant exhibits a V-shaped temperature dependence, negative in the low temperature range, 273-470 K (the rate constant decreases with temperature), and positive in the elevated temperature range, 470-837 K (the rate constant increases with temperature), with a turning point at 471 K. The rate constant could be fairly well fitted with the three parameter modified Arrhenius expression, k 1 = 7.52 × 10-18 (T/298)9 exp(34 367 J mol-1/RT) cm3 per molecule per s (273-837 K). Previously, only one indirect experimental measurement at a single (ambient) temperature was available. The temperature dependence over an extended temperature range obtained in this study together with the peculiar V-shaped temperature dependence will have an impact on the modelling of the flame inhibition by phosphates as well on the further understanding of the mechanisms of elementary chemical reactions.

Superior adjuvanticity of the genetically fused D1 domain of Neisseria meningitides Ag473 lipoprotein among three Toll-like receptor ligands.

Toll-like receptor (TLR) ligands have emerged as the attractive adjuvant for subunit vaccines. However, selection of TLR ligands needs to be rationally chosen on the basis of antigen and adjuvant properties. In the present study, we expressed the Ag473 lipoprotein from Neisseria meningitides, flagellin FlaB from Vibrio vulnificus and heat shock protein 70 from Mycobacterium tuberculosis (mHsp70) in Escherichia coli as single proteins and fusion proteins with VP2 protein of infectious bursal disease virus (IBDV). Both cellular and humoral adjuvanticities of the three TLR ligands were compared by immunization of mice in two different ways. Among the three co-administered TLR ligands, recombinant Ag473 lipoprotein exhibited the highest cellular and humoral adjuvanticities, including promotion of IL-4, IL-12, IFN-γ and IBDV VP2-specific antibody production. Among the three genetically fused TLR ligands, fusion with Ag473 D1 domain exhibited the highest cellular and humoral adjuvanticities. Overall, the adjuvanticities of genetically fused TRL ligands were significantly higher than that of co-administered TLR ligands. Fusion with Ag473 D1 domain exhibited superior adjuvanticity among the three TLR ligands delivered in two different ways.