GPR41 deficiency aggravates type 1 diabetes in streptozotocin-treated mice by promoting dendritic cell maturation.

Disturbances in intestinal immune homeostasis predispose susceptible individuals to type 1 diabetes (T1D). G-protein-coupled receptor 41 (GPR41) is a receptor for short-chain fatty acids (SCFAs) mainly produced by gut microbiota, which plays key roles in maintaining intestinal homeostasis. In this study, we investigated the role of GPR41 in the progression of T1D. In non-obese diabetic (NOD) mice, we found that aberrant reduction of GPR41 expression in the pancreas and colons was associated with the development of T1D. GPR41-deficient (Gpr41-/-) mice displayed significantly exacerbated streptozotocin (STZ)-induced T1D compared to wild-type mice. Furthermore, Gpr41-/- mice showed enhanced gut immune dysregulation and increased migration of gut-primed IFN-γ+ T cells to the pancreas. In bone marrow-derived dendritic cells from Gpr41-/- mice, the expression of suppressor of cytokine signaling 3 (SOCS) was significantly inhibited, while the phosphorylation of STAT3 was significantly increased, thus promoting dendritic cell (DC) maturation. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (BMDC) from Gpr41-/- mice accelerated T1D in irradiated NOD mice. We conclude that GPR41 is essential for maintaining intestinal and pancreatic immune homeostasis and acts as a negative regulator of DC maturation in T1D. GPR41 may be a potential therapeutic target for T1D.

G protein coupled receptor 41 regulates fibroblast activation in pulmonary fibrosis via Gαi/o and downstream Smad2/3 and ERK1/2 phosphorylation.

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease with mysterious pathogenesis and limited effective therapies. G protein-coupled receptors (GPRs) participate in a variety of physiologic functions, and several GPRs have critical fibrosis-promoting or -inhibiting roles in pulmonary fibrosis. Here, we explored the role of GPR41 in the pathobiology of pulmonary fibrosis. We found that GPR41 expression was elevated in lung tissues of mice with bleomycin-induced pulmonary fibrosis and lung fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Knockout of GPR41 attenuated pulmonary fibrosis in mice, as evidenced by improved lung morphology, decreased lung weight and collagen secretion, and down-regulated α-SMA, collagen type I alpha and fibronectin expression in lungs. Additionally, GPR41 knockout inhibited the differentiation of fibroblasts to myofibroblasts, and decreased myofibroblast migration. By further mechanistic analysis, we demonstrated that GPR41 regulated TGF-ß1-induced fibroblast-to-myofibroblast differentiation and Smad2/3 and ERK1/2 phosphorylation via its Gαi/o subunit but not Gßγ subunit. Together, our data indicate that GPR41 is involved in pulmonary fibroblast activation and fibrosis, and GPR41 represents a potential therapeutic target for pulmonary fibrosis.

HIV Disclosure Among Sexually Infected People Living with HIV and AIDS in China: Prevalence, Influencing Factors, and Negative Outcomes.

HIV disclosure is crucial for HIV prevention and control, but may also lead to discrimination, insult, and even violence against people living with HIV and AIDS (PLWHAs). In this study, we examined HIV disclosure, its influencing factors, and its association with intimate partner violence (IPV) among 1153 PLWHAs through the sexual route in Jinan, Shandong Province, China. Our results showed that 76.4% (881/1153) PLWHAs had disclosed someone about their HIV infection, the HIV disclosure rates among family members, friends, spouses, and current fixed partners of PLWHAs were 43.5% (501/1153), 47.9% (552/1153), 56.8% (129/227), and 43.2% (336/777), respectively. HIV disclosure was affected by socio-demographics, disease characteristics, and psycho-social factors and varied among family members, close friends, spouses, and current fixed sexual partners. Age ≤ 33 years (aOR 1.79, 95% CI 1.27-2.53), heterosexual infection route (aOR 1.52, 95% CI 1.06-2.17), HIV diagnosis time > 36 months (aOR 1.84, 95% CI 1.30-2.59), with other chronic diseases (aOR 1.87, 95% CI 1.34-2.61), lower self-stigma (aOR 4.03-4.36, 95% CI 1.98-8.74), higher social support (aOR 1.71-1.73, 95% CI 1.03-2.83), no depression (aOR 1.54, 95% CI 1.12-2.11), and no suicidal ideation (aOR 1.79, 95% CI 1.28-2.50) were all independently associated with increased likelihood of HIV disclosure. HIV disclosure was associated with an increased risk of IPV among current fixed sexual partners (aOR 1.87, 95% CI 1.38-2.54) and spouses (aOR 2.54, 95% CI 1.41-4.56). Our findings suggest that the HIV disclosure rate of PLWHAs is still low and is affected by multiple factors. There is an urgent need to design targeted and comprehensive interventions to improve HIV disclosure. IPV prevention should also be incorporated into the intervention system of HIV disclosure to ensure adequate and continuous support for PLWHAs.

Efficacy of Tailor-Made Notched Music Training Versus Tinnitus Retraining Therapy in Adults With Chronic Subjective Tinnitus: A Randomized Controlled Clinical Trial.

OBJECTIVES: Chronic subjective tinnitus can have a serious effect on daily life, even causing serious psychological disorders. Currently there are no specific effective solutions or cures. Tailor-made notched music training (TMNMT) is a recently proposed sound therapy that has simpler processes and a higher compliance rate than tinnitus retraining therapy (TRT), a widely used treatment for chronic subjective tinnitus. This study explores the therapeutic effect of TMNMT in comparison to TRT to highlight its clinical value. DESIGN: The study was a randomized controlled, single-blinded clinical trial. One hundred twenty eligible participants were randomly assigned to receive TMNMT (n = 60) or TRT (n = 60) for 3 mo with concurrent follow-up. It should be noted that the duration of sound treatment in TRT was modified to 2 hr per day for better feasibility in practice. The primary outcome was mean change in tinnitus handicap inventory (THI) measured at baseline ( T0 ), 1 mo ( T1 ) and 3 mo ( T2 ) after intervention. Change in visual analog scale (VAS) was measured as a secondary outcome. A comparison of therapeutic effectiveness between TMNMT and TRT was evaluated by repeated measure analysis of variance. RESULTS: One hundred and twelve (93%) of participants took part in the study, of which 64 were men and 48 women. Mean (SD) age was 42.80 (12.91) years. Fifty-eight were allocated to receive TMNMT and 54 to receive TRT. The between-group difference in primary outcome was -6.90 points (95% confidence interval [CI], -13.53 to -0.27) at T1 and -6.17 points (95% CI, -13.04 to 0.71) at T2 . These results closely reached to clinical significance of tinnitus-related effective relief. For the secondary outcome, the mean value in the TMNMT group was 0.83 points (95% CI, 0.12 to 1.54), significantly lower than the mean value of the TRT group. The differences in THI and VAS between the two groups were statistically significant after intervention. Further analysis showed that age and baseline THI and VAS scores were associated with change in THI and VAS scores after interventions. CONCLUSIONS: Both TMNMT and TRT were able to alleviate chronic subjective tinnitus effectively after a 3 month intervention. When the two forms of therapy were compared TMNMT appeared to be more effective and consequently potentially superior to TRT for reducing tinnitus loudness and functional and emotional disturbance associated with chronic subjective tinnitus.

Intimate partner violence and its associations among HIV-infected MSM with new drug abuse in Jinan, China.

BACKGROUND: Intimate Partner Violence (IPV) is prevalent among HIV-infected men who have sex with men (MSM), with well-established risk factors and adverse outcomes. However, there is a lack of comprehensive investigation of both upstream risk factors and downstream adverse outcomes among HIV-infected MSM in a Chinese context. This study aimed to examine IPV and its associations among a Chinese sample of HIV-infected MSM. METHODS: A cross-sectional study was conducted among 294 HIV-infected MSM in Jinan City from June to December 2020. All data were collected through an online questionnaire, which included IPV, sexual risk behavior, antiretroviral therapy (ART) adherence, depression, anxiety, and suicidal ideation. Chi-square tests and multivariate logistic regressions were performed to examine risk factors and adverse outcomes of IPV. RESULTS: Of the 294 HIV-infected MSM, 71.1% experienced any IPV, including control (37.1%), threat of public identity (30.6%), emotional violence (25.2%), security threat (18.4%), and physical violence (13.9%). The prevalence of sexual risk behavior, good ART adherence, depression, anxiety, and suicidal ideation was 55.1%, 53.4%, 48.3%, 32.3%, and 65.0%, respectively. Abuse of methamphetamine (METH) (aOR:2.79; 95%CI:1.43 ~ 5.45), capsule 0 or stimulating liquid (aOR:2.68; 95%CI:1.31 ~ 5.47), Magu (aOR:3.16; 95%CI:1.51 ~ 6.60), and other new drugs (aOR:2.87; 95%CI:1.52 ~ 5.43), disclosing HIV infection to partners (aOR:2.03; 95%CI:1.10 ~ 3.78), and gay sexual orientation (aOR = 3.32; 95%CI: 1.82 ~ 6.05) were significantly correlated with the experience of IPV. In addition, IPV was significantly associated with sexual risk behavior (aOR = 2.02; 95%CI:1.16 ~ 3.53), ART adherence (aOR = 2.63; 95%CI:1.46 ~ 4.74), depression (aOR = 3.83; 95%CI:2.09 ~ 7.02), anxiety (aOR = 2.27; 95%CI:1.19 ~ 4.35), and suicidal ideation (aOR = 3.78; 95%CI:2.11 ~ 6.80). CONCLUSIONS: IPV is prevalent among HIV-infected MSM and is associated with poor behavioral and mental health, highlighting more efforts are needed to address this issue. The finding that new drug abuse, HIV disclosure, and gay sexual orientation are associated with increased risk of IPV provides essential insights for the development of comprehensive and targeted IPV prevention and intervention programs in the future.

Characteristics of tympanogram in symptomatic Eustachian tube dysfunction.

PURPOSE: To identify the characteristics of tympanogram in symptomatic Eustachian tube dysfunction (SETD) patients. METHODS: One hundred and twenty-four unilateral SETD patients presenting with type A tympanograms who underwent balloon dilation of the Eustachian tube (BDET) were recruited and assigned into effective BDET group and ineffective BDET group based on treatment effect. The unaffected ear in the same patient served as normal control. Fifty-one patients with sudden sensorineural hearing loss (SSHL) and 46 patients with Meniere's disease (MD) were selected for cases of non-ETD ear fullness. Demographics, 7-item Eustachian Tube Dysfunction Questionnaire score (ETDQ-7), and tympanograms were recorded and analyzed preoperatively and postoperatively. RESULTS: Of the 124 SETD patients included in the study 94 (75.8%) showed good response to BDET based on decreased ETDQ-7 scores. There were no significantly differences in the values of tympanometric peak pressure (TPP) between diseased ears and healthy ears in SETD patients, as well as in SSHL and MD patients. Instead, TPP shifts (the difference between two values of TPP obtained under a Valsalva and Toynbee maneuver) were remarkably reduced in affected ears compared with those in unaffected ears in effective BDET group at baseline. Moreover, TPP shifts in these SETD ears significantly raised and reached the levels in healthy ears postoperatively. CONCLUSIONS: This study demonstrated TPP shifts are decreased in a subset of SETD patients presenting with type A tympanograms and these patients are more likely to show good response to BDET.

BODIPY Photocatalyzed Beckmann Rearrangement and Hydrolysis of Oximes under Visible Light.

A novel, efficient, and mild protocol for rearrangement of oximes to amides or hydrolyzing to ketone/aldehyde using a simple BODIPY dye as a photocatalyst and air as an oxidant via propagation reaction under visible-light irradiation is reported. The triplet excited state of BODIPY played a significant role in the catalytic process. It was found that the various substituted ketoximes, both with electron-withdrawing and electron-donating substituents, afforded the corresponding products with moderate to excellent yields, and the catalytic efficiency was up to 0.01 mol %.

Energetic Systematics of Metal-Organic Frameworks: A Case Study of Al(III)-Trimesate MOF Isomers.

Thermal stability and thermodynamic properties of aluminum(III)-1,3,5-benzenetricarboxylate (Al-BTC) metal-organic frameworks (MOFs), including MIL-96, MIL-100, and MIL-110, have been investigated through a suite of calorimetric and X-ray techniques. In situ high-temperature X-ray diffraction (HT-XRD) and thermogravimetric analysis coupled with differential scanning calorimetry (TGA-DSC) revealed that these MOFs undergo thermal amorphization prior to ligand combustion. Thermal stabilities of Al-BTC MOFs follow the increasing order MIL-110 < MIL-96 < MIL-100, based on estimated amorphization temperatures. Their thermodynamic stabilities were directly measured by high-temperature drop combustion calorimetry. Normalized (per mole of Al) enthalpies of formation (ΔH*f) of MIL-96, MIL-100, and MIL-110 from Al2O3, H3BTC, and H2O (only Al2O3 and H3BTC for MIL-100) were determined to be -56.9 ± 13.7, -36.2 ± 17.9, and 62.8 ± 11.6 kJ/mol·Al, respectively. Our results demonstrate that MIL-96 and MIL-100 are thermodynamically favorable, while MIL-110 is metastable, in agreement with thermal and hydrothermal stability trends. The enthalpic preferences of MIL-96 and MIL-100 may be attributed to their shared trinuclear µ3-oxo-bridged (Al3(µ3-O)) secondary building units (SBUs) promoting stabilization of Al polyhedra by the ligands within these frameworks, in comparison to the sterically strained Al8 octamer cluster cores formed in MIL-110. Furthermore, similar ΔH*f of MIL-96 and MIL-100 explain their concurrent formation as physical mixtures often encountered during synthesis, implying the importance of kinetic factors that may facilitate the formation of Al-BTC framework isomers. More importantly, the normalized formation enthalpies of Al-BTC MOF isomers follow a negative correlation with the ratio of charged coordinated substituents to linkers (normalized per mole of Al within the MOF formula unit), with enthalpic preference given to systems with smaller (O2- + OH-)/ligand ratios. This trend has been successfully extended to the previously measured ΔH*f of several Zn4O-based frameworks (e.g., MOF-5, MOF-5(DEF), MOF-177, UMCM-1), all of which have been found to be metastable with respect to their dense phases (ZnO, H2O, and ligands). The result suggests that carboxylate MOFs with higher metal coordination environments attain more enthalpic stabilization from the coordinated ligands. Thus, the formation of some lanthanide/actinide, transition metal, and main group carboxylate frameworks may be energetically more favored, which, however, requires further studies.

Alterations of brain activity and functional connectivity in transition from acute to chronic tinnitus.

The objective of this study was to investigate alterations to brain activity and functional connectivity in patients with tinnitus, exploring neural features in the transition from acute to chronic phantom perception. Twenty-four patients with acute tinnitus, 23 patients with chronic tinnitus, and 32 healthy controls were recruited. High-density electroencephalography (EEG) was used to explore changes in brain areas and functional connectivity in different groups. When compared with healthy subjects, acute tinnitus patients had a significant reduction in superior frontal cortex activity across all frequency bands, whereas chronic tinnitus patients had a significant reduction in the superior frontal cortex at beta 3 and gamma frequency bands as well as a significant increase in the inferior frontal cortex at delta-band and superior temporal cortex at alpha 1 frequency band. When compared to the chronic tinnitus group, the acute tinnitus group activity was significantly increased in the middle frontal and parietal gyrus at the gamma-band. Functional connectivity analysis showed that the chronic tinnitus group had increased connections between the parahippocampus gyrus, posterior cingulate cortex, and precuneus when compared with the healthy group. Alterations of local brain activity and connections between the parahippocampus gyrus and other nonauditory areas appeared in the transition from acute to chronic tinnitus. This indicates that the appearance and development of tinnitus is a dynamic process involving aberrant local neural activity and abnormal connectivity in multifunctional brain networks.

Solvent-Free and Phase-Selective Synthesis of Aluminum Trimesate Metal-Organic Frameworks.

Aluminum-based metal-organic frameworks (Al-MOFs) have shown promise as commercially valuable materials due to the variety of applications, excellent thermal, hydrothermal, and chemical stabilities, and the abundance of aluminum. In this work, for the first time, we report the solvent-free synthesis of the aluminum trimesate (Al-BTC) MOFs (MIL-100(Al), MIL-96(Al), and MIL-110(Al)) with phase selectivity and high yield. These MOFs were traditionally prepared with HF, HNO3, and bulk solvents, but these methods struggled to produce pure-phase isolations. The solvent-free strategy provides valuable insight into the future industrial scale-up production of the Al-MOFs and promotes the potential commercialization of such materials.

Synthetic reactions driven by electron-donor-acceptor (EDA) complexes.

The reversible, weak ground-state aggregate formed by dipole-dipole interactions between an electron donor and an electron acceptor is referred to as an electron-donor-acceptor (EDA) complex. Generally, upon light irradiation, the EDA complex turns into the excited state, causing an electron transfer to give radicals and to initiate subsequent reactions. Besides light as an external energy source, reactions involving the participation of EDA complexes are mild, obviating transition metal catalysts or photosensitizers in the majority of cases and are in line with the theme of green chemistry. This review discusses the synthetic reactions concerned with EDA complexes as well as the mechanisms that have been shown over the past five years.

Effectiveness and Safety of an Inactivated Enterovirus 71 Vaccine in Children Aged 6-71 Months in a Phase IV Study.

BACKGROUND: Evaluation of a licensed inactivated enterovirus type 71 (EV71) vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. METHODS: An open-label, controlled trial involving a large population of 155 995 children aged 6-71 months was performed; 40 724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected cases with hand, foot, and mouth disease were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th day postinoculation through the local database of the Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71-infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. RESULTS: An overall level of 89.7% (95% confidence interval, 24.0-98.6%) vaccine effectiveness against EV71 infection and a 4.58% rate of reported adverse events were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. CONCLUSIONS: The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. CLINICAL TRIALS REGISTRATION: NCT03001986.

Lysine-specific demethylase-1 regulates fibroblast activation in pulmonary fibrosis via TGF-ß1/Smad3 pathway.

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease with mysterious pathogenesis and limited effective therapies. The aberrantly activated lung myofibroblasts with resultant excessive accumulation of extracellular matrix is a central event in the progression of pulmonary fibrosis. Lysine-specific demethylase 1 (LSD1) has been suggested to epigenetically regulate cell differentiation, migration and invasion in tumor microenvironment. However, its function in pulmonary fibrosis remains unclear. The present study aimed to investigate the potential effect and underlying mechanisms of LSD1 in pulmonary fibrosis. Here, we found that LSD1 expression was elevated in lung tissues of mice with bleomycin-induced pulmonary fibrosis and lung fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). In vivo knockdown of LSD1 by lentiviral shRNA transfection attenuated pulmonary fibrosis in mice, as evidenced by improved lung morphology, decreased lung coefficient and collagen secretion, and down-regulated α-SMA, collagen type I alpha and fibronectin expression in lungs. Additionally, in vitro knockdown of LSD1 inhibited the differentiation of fibroblasts to myofibroblasts, and decreased myofibroblast migration. By further mechanistic analysis, we demonstrated that knockdown of LSD1 prevented fibroblast--to-myofibroblast differentiation and subsequent pulmonary fibrosis by suppressing TGF-ß1/Smad3 signaling pathway through modulation of a balance between histone H3 lysine 9 methylation and histone H3 lysine 4 methylation. Together, our data indicate that LSD1 activation contributes to pulmonary myofibroblast differentiation and fibrosis by targeting TGF-ß1/Smad3 signaling, and suggest LSD1 as a therapeutic target for the treatment of pulmonary fibrosis.

A two-stage water allocation strategy for developing regional economic-environment sustainability.

In this study, a new two-stage stochastic interval-parameter fuzzy programming strategy model is developed for regional economic-environment sustainability, considering the planning and management of water-resources and water-environment systems under uncertainty. The model is capable in addressing the complexity and uncertainties of the water system，which contains the concepts of economics and environment within an optimization framework. The objective of this research is to develop a participatory integrated assessment model, based on the water benefit and water environment security, with an application in the Sanjiang Plain area, China. The methodology intendeds to capture the complexity and scarcity of water management problems, incorporating the relevant sectors, as well as the different levels of water involved in water management decision. The model is applied through maximizing the benefits of water during livelihood, production and ecology. In addition, the model considers the constraints of water quantity and water quality. Then, a variety of decision results are calculated under different conditions of water shortage. The developed method is applied to plan resources management and develop regional environment sustainability. The generated results can assist the decision makers in not only making resources allocation strategies but also gaining insights into the benefit between economic and environment objective.

Bisphenol-A inhibits improvement of testosterone in anxiety- and depression-like behaviors in gonadectomied male mice.

Bisphenol-A (BPA) is a well-known environmental endocrine disruptor. Developmental exposure to BPA affected a variety of behaviors in multiple model organisms. Our recent study found that exposure to BPA during adulthood aggravated anxiety- and depression-like states in male mice but not in females. In this study, 11-w-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5 mg/kg), TP and BPA (0.04, 0.4, or 4 mg/kg), or vehicle for 45 days. BPA (0.4 or 4 mg/kg) did not affect the elevated plus maze task of GDX mice but shortened the time on open arms and decreased the frequency of head dips of sham and TP-GDX mice. In forced swim task, BPA prolonged the total time of immobility of both sham and TP-GDX mice but not GDX mice. In addition, BPA reduced the levels of T in the serum and the brain of sham and TP-GDX mice. Western blot analysis further showed that BPA reduced the levels of androgen receptor (AR) and GABA(A)α2 receptor of the hippocampus and the amygdala in sham and inhibited the rescue of TP in these proteins levels of GDX mice. Meanwhile, BPA decreased the level of phospho-ERK1/2 in these two brain regions of sham and TP-GDX mice. These results suggest that long-term exposure to BPA inhibited TP-improved anxiety- and depression-like behaviors in GDX male mice. The down-regulated levels of GABA(A)α2 receptor and AR and an inhibited activity of ERK1/2 pathway in the hippocampus and the amygdala may be involved in these process.

Cumulibacter manganitolerans gen. nov., sp. nov., isolated from sludge of a manganese mine.

A Gram-stain-positive actinobacterium, designated as strain 2-36T, was isolated from sludge of a sewage outlet in a manganese mine. Phylogenetic analysis of 16S rRNA genes assigned strain 2-36T in a single lineage in the family Geodermatophilaceae and closely related to Modestobacter roseus KLBMP 1279T (93.8 % similarity), Blastococcus saxobsidens BC444T (93.1 %) and Geodermatophilus aquaeductus BMG801T (92.8 %). It contained iso-C16 : 0, iso-C15 : 0, C17 : 1ω6c, iso-C14 : 0 and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) as the major fatty acids (>5 %), with MK-9(H4), MK-8(H4) and MK-9(H6) as the quinones. The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid and the DNA G+C content was 70.1 mol%. The polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, an unknown glycolipid, an unknown aminophospholipid and two unknown phospholipids. Compared to closely related strains, strain 2-36T showed distinguishing characteristics, such as the distinct phylogenetic lineage, positive result for phenylacetic acid assimilation and negative result for α-glucosidase and having C17 : 1ω6c and iso-C14 : 0 as the major fatty acids. On the basis of the polyphasic analyses, strain 2-36T represents a novel species of a new genus within the family Geodermatophilaceae, for which the name Cumulibacter manganitolerans gen. nov., sp. nov. is proposed. The type strain of 'Cumulibacter manganitolerans' is 2-36T (=CCTCC AA 2016026T=DSM 103787T).

Pseudaminobacter manganicus sp. nov., isolated from sludge of a manganese mine.

A Gram-staining-negative, aerobic, non-motile, capsule-forming and rod-shaped bacterium, designated JH-7T, was isolated from sludge of a manganese mine. The 16S rRNA gene sequence of JH-7T showed highest similarities to those of Pseudaminobacter salicylatoxidans BN12T (97.4 %), Mesorhizobiumthiogangeticum SJTT (97.0 %) and Pseudaminobacter defluvii THI 051T (96.5 %). Phylogenetic trees clustered JH-7T together with P. salicylatoxidans BN12Tand P. defluvii THI 051T. The DNA-DNA hybridization values between JH-7T and P. salicylatoxidans DSM 6986T and between JH-7T and M. thiogangeticum DSM 17097T were 34.8 and 20.1 %, respectively. The major fatty acids of JH-7T (>10 %) were C18 : 1ω7c, C19 : 0cyclo ω8c and C16 : 0. The genomic DNA G+C content was 61.6 mol%. The polyamines of JH-7T were sym-homospermidine (83 %) and putrescine (17 %), and the respiratory quinone was ubiquinone-10. The major polar lipids were phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, two unidentified aminolipids and two unidentified lipids. Compared with the members of the genera Pseudaminobacter and Mesorhizobium, JH-7T showed some unique physiological and biochemical characters, such as being negative for H2S production, hydrolysis of Tween 40 and Tween 60, esterase lipase (C8) activity and assimilation of d-ribose and positive for acid production from d-galactose and assimilation of d-fructose. On the basis of the results of the polyphasic taxonomic analysis, JH-7T was considered to represent a novel species of the genus Pseudaminobacter, for which the name Pseudaminobacter manganicus sp. nov. is proposed. The type strain is JH-7T (=KCTC 52258T=CCTCC AB 2016107T).

Cytotoxic and Antitumor Effects of Curzerene from Curcuma longa.

Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicine Curcuma rhizomes. In this study, anticancer activity of curzerene was examined in both in vitro and in vivo models. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer IC50s were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effects in vivo. In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in both in vitro and in vivo models. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development.