[Advances in Nanotechnology-Based Drug Delivery Systems in the Treatment of Hepatocellular Carcinoma].

Primary liver cancer is one of the most common malignant tumors of the digestive system,of which hepatocellular carcinoma (HCC) accounts for more than 90% of the total cases.The patients with early HCC treated by surgical resection generally demonstrate good prognosis.However,due to the insidious onset,HCC in the vast majority of patients has progressed to the mid-to-late stage when being diagnosed.As a result,surgical treatment has unsatisfactory effects,and non-surgical treatment methods generally have severe side effects and low tumor selectivity.Nanoparticles (NP) with small sizes,large specific surface areas,and unique physical and chemical properties have become potential carriers for the delivery of therapeutic agents such as drugs,genes,and cytokines.The nano-delivery systems with NP as the carrier can regulate the metabolism and transformation of drugs,genes,and cytokines in vivo from time,space,and dose via functional modification,showing great potential in the treatment of HCC.This paper introduces the current status and advantages of several common nano-delivery systems,including organic nano-carriers,inorganic nano-carriers,and exosomes,in the treatment of HCC.Furthermore,this paper summarizes the mechanisms of NP-based nano-carriers in treating HCC and provides reference for the development of new nano-delivery systems.

A retrospective analysis of 25 cases of Addison's disease caused by adrenal tuberculosis in Tibet and review of related literature.

Background: To investigate the clinical characteristics of Addison's disease caused by adrenal tuberculosis in Tibet. After the anti-tuberculosis treatment, the clinical features between continuous glucocorticoid therapy and glucocorticoid withdrawal were analyzed. Methods: Clinical data of patients with Addison's disease caused by adrenal tuberculosis diagnosed in The People's Hospital of Tibet Autonomous Region from January 2015 to October 2021 were collected and analyzed. All patients were taking anti-tuberculosis and glucocorticoids replacement therapy, and the root cause of the disease was analyzed following prognosis observations. Results: There were 25 patients (24 Tibetan and 1 Han patient) with Addison's disease caused by adrenal tuberculosis, including 18 males and 7 females. A total of 21 cases were followed up successfully, of which 13 cases discontinued anti-tuberculosis drugs successfully, 6 cases discontinued glucocorticoid therapy among the rest, 6 cases continued anti-tuberculosis + glucocorticoid replacement therapy, and 2 cases died. Conclusion: Early diagnosis and proper anti-tuberculosis treatment can improve the prognosis of patients with adrenal tuberculosis. Moreover, screening and educating Tibetan people regarding the potential risk and adversities of adrenal tuberculosis is crucial for eradicating the disease.

Hsa_circ_0045932 regulates the progression of colorectal cancer by regulating HK2 through sponging miR-873-5p.

BACKGROUND: Circular RNAs (circRNAs) have been confirmed to be key regulators for colorectal cancer (CRC) progression. The purpose of this research was to explore the biological role and mechanism of hsa_circ_0045932 in CRC. METHODS: RT-qPCR and Western blot (WB) were applied to examine RNA and protein levels, respectively. MTT assay, EdU assay, and transwell assay were used to detect cell proliferative, migration, and invasion. Glucose uptake and lactic acid level were determined to assess cellular glycolysis. Dual-luciferase reporter and RIP assays were carried out to detect the relationship between miR-873-5p and hsa_circ_0045932 or hexokinase 2 (HK2). Xenograft mice model was established to confirm the function of hsa_circ_0045932 in vivo. RESULTS: Hsa_circ_0045932 was overexpressed in CRC tissue samples and cells. Hsa_circ_0045932 knockdown repressed CRC cell proliferation, invasion, migration, and glycolysis abilities in vitro. MiR-873-5p could be sponged by hsa_circ_0045932, and its inhibitor also reversed the inhibitory effect of hsa_circ_0045932 knockdown on CRC cell progression. HK2 was targeted by miR-873-5p, and hsa_circ_0045932 regulated HK2 expression through targeting miR-873-5p. Overexpression of HK2 reversed the repressive effect of hsa_circ_0045932 knockdown on CRC cell malignant behaviors. Furthermore, the pro-tumor role of hsa_circ_0045932 in vivo was also confirmed using animal experiments. CONCLUSION: Hsa_circ_0045932 promoted CRC progression through sponging miR-873-5p to up-regulate HK2, which might offer novel therapeutic target for CRC clinical intervention.

Facile synthesis of mesoporous ZSM-5 aided by sonication and its application for VOCs capture.

Application of ultrasound power to the mother liquor is popular pretreatment for zeolite synthesis which offers a simple way of accelerating crystallization process and finetuning the properties of nanocrystalline zeolites. In this work, sonication-aided synthesis of mesoporous ZSM-5 at low temperature and ambient pressure was systematically studied, in an attempt to reach efficient and benign synthesis of zeolites with hierarchical pore structure, which has wide applications as catalysts and sorbents. The effects of sonication duration, power density, sonication temperature and seeding on the crystallization of ZSM-5 were investigated. The obtained samples were characterized by XRD, SEM, BET and VOCs capture. High quality mesoporous ZSM-5 can be obtained by a facile 5 d synthesis at 363 K, much faster than conventional hydrothermal synthesis. The reduced synthesis time was mainly attributed to the enhanced crystallization kinetics caused by the fragmentation of seeds and nuclei, while sonication radiation had little impact on the nucleation process. Compared with control sample, mesoporous ZSM-5 prepared by sonochemical method had higher surface area and mesoporosity which demonstrated improved adsorption performance for the capture of isopropanol.

Exogenous inoculation of endophytic bacterium Bacillus cereus suppresses clubroot (Plasmodiophora brassicae) occurrence in pak choi (Brassica campestris sp. chinensis L.).

MAIN CONCLUSION: The presence of Bacillus cereus plays a key role in clubroot suppression and improves plant biomass in pak choi. B. cereus is reported for the first time as a novel biocontrol agent against clubroot. Plasmodiophora brassicae Woronin causes a devastating infectious disease known as clubroot that is damaging to cruciferous vegetables. This study aimed to isolate beneficial bacteria from the rhizosphere soil of pak choi (Brassica campestris sp. chinensis) and to evaluate the ability of the isolate to reduce the severity of clubroot. Strains obtained from the rhizosphere of symptomless pak choi were first selected on the basis of their germination inhibition rate and effects on the viability of P. brassicae resting spores. Eight bacterial isolates had inhibitory effects against the resting spores of clubroot causing pathogen. However, MZ-12 showed the highest inhibitory effect at 73.4%. Inoculation with MZ-12 enhanced the plant biomass relative to plants grown without MZ-12 as well as P. brassicae infected plants. Furthermore, enhanced antioxidant enzymatic activities were observed in clubroot-infected plants during bacterial association. Co-inoculation of the plant with both P. brassicae and MZ-12 resulted in a 64% reduction of gall formation in comparison to plants inoculated with P. brassicae only. Three applications of MZ-12 to plants infected with P. brassicae at 7, 14 and 21 days after seeding (DAS) were more effective than one application and repressed root hair infection. According to 16S rDNA sequence analysis, strain MZ-12 was identified as had a 100% sequence similarity with type strain Bacillus cereus. The findings of the present study will facilitate further investigation into biological mechanisms of cruciferous clubroot control.

KHK-A promotes the proliferation of oesophageal squamous cell carcinoma through the up-regulation of PRPS1.

BACKGROUND AND STUDY AIMS: The metabolism of dietary fructose by ketohexokinase (KHK) is an important step in glucose metabolism in various tumour types. However, the expression, function and underlying mechanisms of KHK in oesophageal squamous cell carcinoma (ESCC) remain largely unclear. The objective of this study was to investigate the effects of KHK-A, a peripheral isoform of KHK, on the proliferation of ESCC cell lines. MATERIAL AND METHODS: The function and mechanism of KHK-A in ESCC cells were investigated by constructing stable KHK-A-knockdown and -overexpressing ESCC cell lines (KYSE410 and KYSE150, respectively). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and colony formation assays were used to analyse the effects of KHK-A on cell proliferation, cell cycle and colony formation, respectively. KHK-A and phosphoribosyl pyrophosphate synthetase isoform 1 (PRPS1) mRNA and protein expressions in several ESCC cell lines were determined using routine reverse transcription-polymerase chain reaction and immunoblotting, respectively. KHK and PRPS1 expressions in ESCC tumour tissues and corresponding adjacent non-tumour tissues were evaluated according to the gene expression omnibus (GEO) database (GSE20347). RESULTS: In vitro experiments showed that KHK-A significantly promoted cell proliferation by modulating the G1/S phase transition in the cell cycle, which was probably regulated by PRPS1 expression. GEO database-based analysis showed that KHK levels were significantly higher in the ESCC tissues than in the corresponding adjacent non-tumour tissues. Pearson's correlation coefficient analysis showed that KHK expression in ESCC cell lines and tissues was significantly positively associated with the up-regulation of PRPS1, suggesting that KHK-A levels regulate PRPS1 expression in ESCC. CONCLUSION: KHK-A may serve as a driving gene in ESCC for the activation of PRPS1, resulting in the up-regulation of PRPS1. This could lead to enhanced nucleic acid synthesis for tumourigenesis. Our study showed that KHK-A is a potential target for ESCC diagnosis and therapy.

Growth and physiological responses of Pennisetum sp. to cadmium stress under three different soils.

Pennisetum sp. was employed as a model species to detect the growth and physiological response to cadmium (Cd) stress at different Cd concentrations (0, 20, 50, and 100 mg kg-1) in three types of soils (yellow brown soil, yellow soil, and red soil). Results showed that the growth of Pennisetum sp. was not significantly influenced by Cd in 20 mg kg-1, but significantly inhibited at higher Cd concentrations in three types of soils. Besides, the higher Cd concentrations, the lower root, stem, and leaf biomass. With Cd concentration of soil increasing, Cd content of root, stem, and leaf increased. Compared with no Cd, high Cd concentrations (50 and 100 mg kg-1) induced the physiological indices (photosynthetic rate, stomatal conductance, transpiration rate) and biochemical indices (nitrate reductase, glutamine synthetase, and glutamate synthase activities) decreasing, but the concentration of NO3- and NH4+ increasing. The activity of antioxidative enzymes (SOD, POD, and CAT) was disrupted and the content of malondialdehyde (MDA) increasing. Pennisetum sp. could protect cells from damage and maintain normal physiological metabolism via increasing the production of soluble sugar and soluble protein, but soluble proteins and soluble sugars were limited in high concentrations of Cd (50 and 100 mg kg-1). Moreover, the growth and physiological response to Cd are different in the three types of soils. The growth of Pennisetum sp. in yellow brown soil was better than that in other two soils, and the gas exchange rate, antioxidant enzyme activity, and nitrogen metabolism in yellow soil and red soil were more affected by Cd stress than that in yellow brown soil. Overall, Pennisetum sp. had certain tolerance and biosorption ability to Cd in different Cd concentrations and different types of soil. Hence, Pennisetum sp. was a suitable choice for Cd remediation, especially in yellow brown soil.

A calmodulin-like CmCML13 from Cucumis melo improved transgenic Arabidopsis salt tolerance through reduced shoot's Na+, and also improved drought resistance.

The calmodulin-like proteins (CMLs) are a large family involved in plant biological processes. A calmodulin-like gene CmCML13 (GenBank accession number: MT340534) from melon (Cucumis melo L.) was isolated and functionally analyzed. CmCML13 was predicted to possess 3 EF-hands in which only the first EF-hand could bind with Ca2+. Subcellular localization assay revealed that CmCML13 was localized in nucleus, cell membrane, vacuolar membrane and cytoplasmic strand. The transcript level of CmCML13 was temporally and spatially regulated under salt stress. Constitutive expression of CmCML13 in the Arabidopsis thaliana enhanced salt tolerance at seeds germination. CmCML13 improved the transgenic Arabidopsis plants salt tolerance by significantly reducing Na+ content of shoots, which was unrelated to HKT1-involving pathway. Moreover, overexpressing of CmCML13 in Arabidopsis showed stronger drought tolerance. This study demonstrates that the CmCML13 is an important multifunctional protein associated with salt and drought stress, which may play a key role in stress signaling pathway.

Supportive role of the Na+ transporter CmHKT1;1 from Cucumis melo in transgenic Arabidopsis salt tolerance through improved K+/Na+ balance.

KEY MESSAGE: CmHKT1;1 selectively exports Na+ from plant cells. Upon NaCl stress, its expression increased in a salt-tolerant melon cultivar. Overexpression of CmHKT1;1 increased transgenic Arabidopsis salt tolerance through improved K+/Na+ balance. High-affinity K+ transporters (HKTs) are thought to be involved in reducing Na+ in plant shoots under salt stress and modulating salt tolerance, but their function in a moderately salt-tolerant species of melon (Cucumis melo L.) remains unclear. In this study, a Na+ transporter gene, CmHKT1;1 (GenBank accession number: MK986658), was isolated from melons based on genome data. The transcript of CmHKT1;1 was relatively more abundant in roots than in stems or leaves from melon seedlings. The tobacco transient expression system showed that CmHKT1;1 was plasma-membrane localized. Upon salt stress, CmHKT1;1 expression was more strongly upregulated in a salt-tolerant melon cultivar, 'Bingxuecui' (BXC) compared with a salt-sensitive cultivar, 'Yulu' (YL). Electrophysiological evidence demonstrated that CmHKT1;1 only transported Na+, rather than K+, when expressed in Xenopus laevis oocytes. Overexpression of CmHKT1;1 increased salt sensitivity in Saccharomyces cerevisiae and salt tolerance in Arabidopsis thaliana. Under NaCl treatments, transgenic Arabidopsis plants accumulated significantly lower concentrations of Na+ in shoots than wild type plants and showed a better K+/Na+ balance, leading to better Fv/Fm, root length, biomass, and enhanced plant growth. The CmHKT1;1 gene may serve as a useful candidate for improving crop salt tolerance.

[Effects of different ratios of n-6/n-3 polyunsaturated fatty acid on adiponectin, glycolipid metabolism and antioxidant capacity in high fat-diet fed rats].

OBJECTIVE: To investigate effects of different ratios of n-6/n-3 Polyunsaturated fatty acid(PUFA) on adiponectin, glycolipid metabolism and antioxidant capacity in high fat-diet fed rats. METHODS: Fixty male Wistar rats were randomly divided into control group(CON, 17% energy from fat, n-6/n-3 PUFA=5∶1) and high-fat treatment groups(1∶1 group∶n-6/n-3 PUFA=1∶1, 5∶1 group, n-6/n-3 PUFA=5∶1, 10∶1 group∶ n-6/n-3 PUFA=10∶1 and 20∶1 group∶ n-6/n-3 PUFA=20∶1, 42% energy from fat). Rats were fed for 12 week. Serum glucose and lipid(0, 4, 8 and 12 week) were detected. Antioxidant indexes(0 and 12 week), adiponectin mRNA and protein expressions in epididymal adipose tissues as well as serum adiponectin(12 week) were measured. RESULTS: Baseline data showed no significant inter-group difference(P>0. 05). 1∶1 and 5∶1 showed no significant changes in serum glucose compared with control at all time points(P>0. 05), while 10∶1 and 20∶1 significantly increased it at the 12 th week(P<0. 05). At the 12 th week, total cholesterol(TC) and triglycerides(TG) in high-fat treatment groups were significantly higher than control(P<0. 01), with 20∶1 showing significant increment of TG compared with other high-fat treatment groups(P<0. 01). At the 12~(th) week, glutathione peroxidase and superoxide dismutase content in high-fat treatment groups all decreased significantly compared with control(P<0. 05), and 20∶1 decreased most. Malondialdehyde content significantly increased in high-fat treatment groups(P<0. 05), and 10∶1 increased most. Adiponectin mRNA expression significantly decreased in 20∶1 compared with control, 1∶1 and 5∶1(P<0. 05). Increment of adiponectin protein expression was significantly shown in 5∶1 compared with other high-fat treatment groups(P<0. 05), while it was most obviously decreased in 20∶1(P<0. 05). CONCLUSION: Lower n-6/n-3 PUFA ratios(1∶1 and 5∶1) contributed to improvement of glycolipid metabolism and antioxidant capacity as well as increment of adiponectin expression of rats fed with high-fat diet.

The performance and microbial community in a slightly alkaline biotrickling filter for the removal of high concentration H2S from biogas.

In this study, high concentration of H2S (i.e., 5000 ppmv) in biogas was effectively removed by a slightly alkaline biotricking filter (BTF) with Polypropylene rings as packing material and oxygen from air as the electron acceptor. The results showed that when the inlet loading of H2S increased from 101.7 to 422.0 g/m3/h, the removal efficiency of H2S decreased from 100.0% to 91.4%, and the maximum elimination capacity (EC) was 386.0 ± 10.5 gH2S/m3/h when empty bed retention time (EBRT) was 1.0 min. The slightly alkaline condition could increase the mass transfer of H2S from gas to liquid phase and avoid the toxic effect of high concentration of H2S, resulting in high removal performance of H2S in the system. With the increase of H2S inlet loading, the ratio of SO42- in bio-desulfurization products gradually decreased, while that of S0 increased. At 101.7-210.7 gH2S/m3/h of inlet loading, SO42- was the dominant product with the ratio of above 50.00%, while S0 became the dominant product with 62.96% at 422.0 gH2S/m3/h of inlet loading. The 16S rDNA sequencing results showed that the dominant genus in the BTF was sulfide-oxidizing bacteria (SOB), with the abundance of SOB decreased with the increase of inlet loading. The dominant genus were Pseudomonas, Halothiobacillus and Sulfurimonas in the BTF at 101.7, 139.8 and 210.7 gH2S/m3/h of inlet loading, respectively. The SOB Sulfurimonas might play an important role for bio-desulfurization of high concentration of H2S in a slightly alkaline BTF under high inlet loading of H2S.

Erythrocytosis and Performance of HbA1c in Detecting Diabetes on an Oxygen-Deficient Plateau: A Population-based Study.

CONTEXT: The hemoglobin A1c (HbA1c) test is a standard test for diabetes screening and diagnosis. OBJECTIVE: To evaluate A1c performance for diabetes screening in high-altitude polycythemia compared to a population with a high proportion of people living in an oxygen-deficient environment. DESIGN: A population-based epidemiological survey was conducted. SETTING: The cities Lhasa and Shigatse were selected. Volunteers were recruited through educational advertisements about diabetes. PARTICIPANTS: A total of 1401 Tibetan adults without known diabetes. INTERVENTIONS: Oral glucose tolerance test (OGTT), HbA1c, and complete blood cell count were performed. Hemoglobin A1c was evaluated using high-performance liquid chromatography, and serum glucose level, using the hexokinase method. MAIN OUTCOME MEASURES: World Health Organization criteria were used to define diabetes and prediabetes. Hemoglobin A1c test performance was evaluated using receiver operating characteristic analysis. RESULTS: The participants' mean age was 44.3 ± 15.0 years; 33.3% of the participants were men and 38.6% lived in urban areas. The prediabetes and diabetes prevalence rates were 7.5% and 3.6%, respectively. The optimal HbA1c cutoff for detecting diabetes was 46 mmol/mol (6.4%), with a sensitivity and specificity of 60.8% and 93.6%, respectively. The cutoff for detecting diabetes was 6.7% (50 mmol/mol) in subjects with high-altitude polycythemia (HAPC). The relationship between red blood cell (RBC) counts and HbA1c was significant (P < 0.001), while there was no correlation between hemoglobin (Hb) and HbA1c (P = 0.085). Multiple linear regression analysis showed that after adjusting for age and fasting serum glucose or 2-hour OGTT (OGTT2h) serum glucose, RBC count and not Hb level was an independent risk factor for HbA1c (ß = 0.140, P < 0.001). CONCLUSIONS: The optimal HbA1c cutoff for detecting diabetes was 46 mmol/mol (6.4%) in Tibet. Red blood cell count was an independent risk factor for elevated HbA1c, and HAPC may affect the predictive ability of HbA1c.

Enhancing the removal of H2S from biogas through refluxing of outlet gas in biological bubble-column.

Biological bubble-column (BBC) is beneficial for elemental sulfur recycle from H2S, but it's difficult to remove high concentration of H2S in biogas efficiently due to the mass transfer limitation of H2S from gas to liquid. In this study, a novel method with refluxing outlet gas in BBC was investigated. The results showed that gas reflux greatly enhanced the removal of high concentration of H2S (about 5000 ppmv) from biogas. The removal efficiency of H2S was 88.0 ± 4.1% with the reflux ratio at 1.0, which was higher than those without gas reflux (58.4 ± 1.0%), when the inlet H2S loading was 143.1 ± 4.5 g/(m3·h). Moreover, the removal capacity of H2S improved significantly with the increase of the reflux ratios from 1.0 to 4.0 and achieved the maximum at 271.8 ± 2.4 g/(m3·h). This might mainly be attributed to longer residence time and enhanced the mass transfer of O2 and H2S from gas to liquid through gas reflux.

CmRAV1 shows differential expression in two melon (Cucumis melo L.) cultivars and enhances salt tolerance in transgenic Arabidopsis plants.

The growth and development of melon (Cucumis melo L.) are severely affected by soil salinization in many areas of the world, but the understanding of the molecular mechanisms underlying salt tolerance in melon remains limited. In this study, a new RAV (related to ABI3/VP1) gene, CmRAV1, was identified in melon. Protein structure homology analysis revealed that CmRAV1 contains an AP2 domain and a B3 domain, and subcellular localization assay revealed that CmRAV1 is localized in the nucleus. The transcript level of CmRAV1 was closely correlated with NaCl treatment, and the expression pattern of CmRAV1 differed between two cultivars (salt-tolerant and salt-sensitive cultivars) under NaCl treatment. In addition, yeasts transformed with CmRAV1 showed notably improved growth on medium containing 200 mM NaCl compared with wild-type ones. The overexpression of CmRAV1 in transgenic Arabidopsis thaliana resulted in enhanced salt tolerance at the seed germination and seedling growth stages. This study demonstrated that the expression of CmRAV1 was associated with saline stress and can potentially be utilized to improve plant salt tolerance.

Safety of Metformin Therapy in Patients with Type 2 Diabetes Living on an Oxygen-Deficient Plateau, Tibet, China.

BACKGROUND: In the general population, the absolute risk of lactic acidosis in patients treated with metformin appears to be low. However, in the Tibetan plateau, an extreme oxygen-deficient environment, there are no data available concerning the safety of metformin. The aim of our study is to assess the safety of metformin in people of the plateau area. METHODS: We conducted an observational cross-sectional study in Tibet. All the 166 subjects were divided into two groups: T2DM+metformin group and T2DM group. Clinical characteristics as well as lactate levels were measured in all subjects. The association between lactate, metformin use, FBG, HbA1c, eGFR, and other potential predictors was evaluated. RESULTS: A total of 166 subjects were enrolled in this study. Average age was 51.7±12.3 years, and the percentage of male participants was 67%. The median level of lactate was 1.89 (1.35-2.91) mmol/L in all the subjects. The mean (±SD) lactate concentration in patients treated with metformin, versus those who were not, was 2.35±1.42 vs 2.29±1.65 mmol/L, respectively (mean difference 0.06 mmol/L, 95% CI: -0.48-0.60, P=0.556). FBG was significantly higher in the high lactate group than in the low lactate group (12.1±4.1 vs. 10.5±4.0 mmol/L, P=0.018). Similarly, HbA1c level was also significantly higher in the high lactate group than in the low lactate group (12.3±2.6 vs. 11.0±3.0%, P=0.008). CONCLUSIONS: In the oxygen-deficient Tibetan plateau, lactate concentration among patients on metformin was not significantly different from patients without metformin. The level of lactate was significantly associated with FBG and HbA1c levels.

The removal of hydrogen sulfide from biogas in a microaerobic biotrickling filter using polypropylene carrier as packing material.

Biological removal of hydrogen sulfide in biogas is an increasingly adopted alternative to the conventional physicochemical processes, because of its economic and environmental benefits. In this study, a microaerobic biofiltration system packed with polypropylene carrier was used to investigate the removal of high concentrations of H2S contained in biogas from an anaerobic digester. The results show that H2S in biogas was removed completely under different inlet concentrations of H2S from 2065 ± 234 to 7818 ± 131 ppmv, and the elimination capacity of H2S in the filter achieved about 122 g H2S/m(3)/h. It was observed that the content of CH4 in biogas increased after the biogas biodesulfurization process, which was beneficial for the further utilization of biogas. The elemental sulfur and sulfate were the main sulfur species of H2S degradation, and elemental sulfur was dominant (about 80 %) under high inlet H2S concentration. The results of terminal restriction fragment length polymorphism (T-RFLP) and fluorescence in situ hybridization (FISH) show that the population of sulfide-oxidizing bacteria (SOB) species in the filter changed with different concentrations of H2S. The microaerobic biofiltration system allows the potential use of biogas and the recovery of elemental sulfur resource simultaneously.

Effect of sulfate addition on methane production and sulfate reduction in a mesophilic acetate-fed anaerobic reactor.

A mesophilic anaerobic moving bed biofilm reactor (MBBR) was operated to evaluate the effect of sulfate addition on methane production and sulfate reduction using acetate as the sole carbon source. The results show that at the organic loading rate of 4.0 g TOC/L/day, the TOC removal efficiencies and the biogas production rates achieved over 95 % and 7000 mL/L/day without sulfate, respectively, and slightly decreased with sulfate addition (500-800 mg/L). Methane production capacities were not influenced significantly with the addition of sulfate, while sulfate reduction efficiencies were not stable with 23-87 % in the acetate-fed reactor. Fluorescent in situ hybridization (FISH) was used to analyze the functional microbial compositions of acetate-degrading methane-producing bacteria (MPB) and sulfate-reducing bacteria (SRB) in the reactor. The results found that as the increase of sulfate concentration, the proportion of Methanomicrobiales increased up to 58 ± 2 %, while Methanosaeta and Methanosarcina decreased. The dominant methanogens shifted into hydrogenotrophic methanogens from even distribution of acetoclastic and hydrogenotrophic methanogens. When hydrogenotrophic methanogens were dominant, sulfate reduction efficiency was high, while sulfate reduction efficiency was low as acetoclastic methanogens were dominant.

Functional analysis of the involvement of apurinic/apyrimidinic endonuclease 1 in the resistance to melphalan in multiple myeloma.

BACKGROUND: Melphalan resistance has been considered one of the major obstacles to improve outcomes in multiple myeloma (MM) therapy; unfortunately, the mechanistic details of this resistance remain unclear. Melphalan is a highly effective alkylating agent which causes many types of DNA lesions, including DNA base alkylation damage that is repaired by base excision repair (BER). We postulated that human apurinic/apyrimidinic endonuclease 1 (APE1), an essential BER enzyme, plays a vital role in acquired melphalan resistance. However, because APE1 is a multifunctional protein with redox activity and acetylation modification in addition to its major repair activity, the particular APE1 function that may play a more important role in melphalan resistance is unknown. METHODS: Two MM cell lines, RPMI-8226 and U266 were used to measure the difference in APE1 levels in melphalan-resistant and sensitive derivatives. APE1 functional mutants for DNA repair, redox and acetylation were employed to investigate the roles of individual APE1 activities in acquired melphalan resistance. RESULTS: Our results indicate that APE1 is overexpressed in both MM melphalan-resistant cells. Knocking down APE1 sensitizes the melphalan resistant MM cells to melphalan treatment. The exogenous expression of DNA repair mutant H309N and acetylation mutant K6R/K7R of APE1 failed to restore the melphalan resistance of the APE1 knockdown RPMI-8226 cells. The AP endonuclease activity and multidrug resistance protein 1 (MDR1) regulatory activity may play roles in the melphalan resistance of MM cells. CONCLUSIONS: The present study has identified that the DNA repair functions and the acetylation modification of APE1 are involved in melphalan resistance of MM cells and has also shed light on future therapeutic strategies targeting specific APE1 functions by small molecule inhibitors.

Biodesulfurization of model compounds and de-asphalted bunker oil by mixed culture.

In this study, complicated model sulfur compounds in bunker oil and de-asphalted bunker oil were biodesulfurized in a batch process by microbial consortium enriched from oil sludge. Dibenzothiophene (DBT) and benzo[b]naphtho[1,2-d]thiophene (BNT1) were selected as model sulfur compounds. The results show that the mixed culture was able to grow by utilizing DBT and BNT1 as the sole sulfur source, while the cell density was higher using DBT than BNT1 as the sulfur source. GC-MS analysis of their desulfurized metabolites indicates that both DBT and BNT1 could be desulfurized through the sulfur-specific degradation pathway with the selective cleavage of carbon-sulfur bonds. When DBT and BNT1 coexisted, the biodesulfurization efficiency of BNT1 decreased significantly as the DBT concentrations increased (>0.1 mmol/L). BNT1 desulfurization efficiency also decreased along with the increase of 2-hydroxybiphenyl as the end product of DBT desulfurization. For real bunker oil, only 2.8 % of sulfur was removed without de-asphalting after 7 days of biotreatment. After de-asphalting, the biodesulfurization efficiency was significantly improved (26.2-36.5 %), which is mainly attributed to fully mixing of the oil and water due to the decreased viscosity of bunker oil.

A new pattern-based method for identifying recent HIV-1 infections from the viral env sequence.

The long asymptomatic stage of HIV infection poses a great challenge in identifying recent HIV infections. This is a bottleneck for monitoring HIV epidemic trends and evaluating the effectiveness of national AIDS control programs. Several serological methods were used to address this issue with some success. Because of high false-positive rates in patients with advanced infection or in ART treatment, UNAIDS still hesitates to recommend their use in routine surveillance. We developed a new pattern-based method for measuring intra-patient viral genetic diversity for determination of recent infections and estimation of population incidence. This method is verified by using several datasets (424 subtype B and 77 CRF07_BC samples) with clearly identified HIV-1 infection times. Pattern-based diversities of recent infections are significantly lower than that of chronic ones. With larger window periods varying from 200 to 350 days, a higher accuracy (90%-95%) not affected by advanced disease nor ART treatment could be obtained. The pattern-based genetic method is supplementary to the existing serology-based assays, both of which could be suitable for use in low and high epidemic regions, respectively.