TFEB activation triggers pexophagy for functional adaptation during oxidative stress under calcium deficient-conditions.

BACKGROUND: Calcium is a ubiquitous intracellular messenger that regulates the expression of various genes involved in cell proliferation, differentiation, and motility. The involvement of calcium in diverse metabolic pathways has been suggested. However, the effect of calcium in peroxisomes, which are involved in fatty acid oxidation and scavenges the result reactive oxygen species (ROS), remains elusive. In addition, impaired peroxisomal ROS inhibit the mammalian target of rapamycin complex 1 (mTORC1) and promote autophagy. Under stress, autophagy serves as a protective mechanism to avoid cell death. In response to oxidative stress, lysosomal calcium mediates transcription factor EB (TFEB) activation. However, the impact of calcium on peroxisome function and the mechanisms governing cellular homeostasis to prevent diseases caused by calcium deficiency are currently unknown. METHODS: To investigate the significance of calcium in peroxisomes and their roles in preserving cellular homeostasis, we established an in-vitro scenario of calcium depletion. RESULTS: This study demonstrated that calcium deficiency reduces catalase activity, resulting in increased ROS accumulation in peroxisomes. This, in turn, inhibits mTORC1 and induces pexophagy through TFEB activation. However, treatment with the antioxidant N-acetyl-l-cysteine (NAC) and the autophagy inhibitor chloroquine impeded the nuclear translocation of TFEB and attenuated peroxisome degradation. CONCLUSIONS: Collectively, our study revealed that ROS-mediated TFEB activation triggers pexophagy during calcium deficiency, primarily because of attenuated catalase activity. We posit that calcium plays a significant role in the proper functioning of peroxisomes, critical for fatty-acid oxidation and ROS scavenging in maintaining cellular homeostasis. These findings have important implications for signaling mechanisms in various pathologies, including Zellweger's syndrome and ageing.

Association of systemic inflammatory response index and plaque characteristics with the severity and recurrence of cerebral ischemic events.

AIM: We aimed to investigate the relationship between systemic inflammatory response index (SIRI) and intracranial plaque features, as well as the risk factors related to the severity and recurrence of cerebral ischemic events. METHODS: We enrolled 170 patients with cerebral ischemic events. Baseline demographic characteristics and laboratory indicators were collected from all participants. All patients were assessed by high-resolution magnetic resonance vessel wall imaging for culprit plaque characteristics and intracranial atherosclerotic burden. Outpatient or telephone follow-up were conducted at 1, 3, and 6 months after discharge. RESULTS: SIRI levels were significantly associated with the enhanced plaque number (r = 0.205, p = 0.007), total plaque stenosis score (r = 0.178, p = 0.020), total plaque enhancement score (r = 0.222, p = 0.004), intraplaque hemorrhage (F = 5.630, p = 0.004), and plaque surface irregularity (F = 3.986, p = 0.021). Higher SIRI levels (OR = 1.892), total plaque enhancement score (OR = 1.392), intraplaque hemorrhage (OR = 3.370) and plaque surface irregularity (OR = 2.846) were independent risk factors for moderate-severe stroke, and these variables were significantly positively correlated with NIHSS (P < 0.05 for all). In addition, higher age (HR = 1.063, P = 0.015), higher SIRI levels (HR = 2.003, P < 0.001), and intraplaque hemorrhage (HR = 4.482, P = 0.008) were independently associated with recurrent stroke. CONCLUSIONS: Higher SIRI levels may have adverse effects on the vulnerability and burden of intracranial plaques, and links to the severity and recurrence of ischemic events. Therefore, SIRI may provide important supplementary information for evaluating intracranial plaque stability and risk stratification of patients.

POH1 induces Smad3 deubiquitination and promotes lung cancer metastasis.

Smad3 is the key mediator of TGF-ß1-triggered signal transduction and the related biological responses, promoting cell invasion and metastasis in various cancers, including lung cancer. However, the deubiquitinase stabilizing Smad3 remains unknown. In this study, we present a paradigm in which POH1 is identified as a novel deubiquitinase of Smad3 that plays a tumor-promoting role in lung adenocarcinoma (LUAD) by regulating Smad3 stability. POH1 markedly increased Smad3 protein levels and prolonged its half-life. POH1 directly interacted and colocalized with Smad3, leading to the removal of poly-deubiquitination of Smad3. Functionally, POH1 facilitated cell proliferation, migration, and invasion by stabilizing Smad3. Importantly, POH1 also promoted liver metastasis of lung cancer cells. The protein levels of both POH1 and Smad3 were raised in the tumor tissues of patients with LUAD, which predicts poor prognosis. Collectively, we demonstrate that POH1 acts as an oncoprotein by enhancing TGF-ß1/Smad3 signaling and TGF-ß1-mediated metastasis of lung cancer.

Systematic pan-cancer analysis of RNF186 with potential implications in progression and prognosis in human cancer.

AIMS: Cancer remains a significant global public health issue. There is growing proof that Ring Finger Protein 186 (RNF186) may play a function in pan-cancer, however, this has not yet been thoroughly determined. This study aims to analyze RNF186 with potential implications in progression and prognosis in human cancer. MATERIALS AND METHODS: A comprehensive bioinformatics approaches combined with experimental verification were used across 33 types of cancers in this study to conduct a pan-cancer investigation of RNF186 from the perspectives of gene expression, prognosis, genomic alterations, immunological markers, gene set, and function. KEY FINDINGS: RNF186 is a valuable prognostic biomarker in several cancer types, especially breast invasive carcinoma (BRCA) and uterine corpus endometrial carcinoma (UCEC). The levels of RNF186 promoter methylation and genetic alterations may be responsible for some cancers' abnormal expression. Furthermore, RNF186 expression was determined to be associated with immune checkpoint genes. Analysis of RNF186-related genes revealed that proteasome and PI3K-AKT signaling pathway were primarily involved in the cellular function of RNF186. Additionally, our research first confirmed that RNF186 may function as an oncogene and contribute to cancer proliferation, migration and invasion in UCEC. In contrast, RNF186 may play an inhibitory role in BRCA progression. This function depends on the ligase activity of RNF186. SIGNIFICANCE: This study suggests that RNF186 is a novel critical target for tumor progression in BRCA and UCEC. It reveals that RNF186 may be associated with tumor immunotherapy, which may provide an effective predictive evaluation of the prognosis of immunotherapy.

Combined Therapy of Low-Dose Angiotensin Receptor-Neprilysin Inhibitor and Sodium-Glucose Cotransporter-2 Inhibitor Prevents Doxorubicin-Induced Cardiac Dysfunction in Rodent Model with Minimal Adverse Effects.

Although cancer-therapy-related cardiac dysfunction (CTRCD) is a critical issue in clinical practice, there is a glaring lack of evidence regarding cardiotoxicity management. To determine an effective and suitable dosage of treatment using angiotensin receptor-neprilysin inhibitors (ARNI) with sodium-glucose cotransporter 2 inhibitors (SGLT2i), we adopted a clinically relevant rodent model with doxorubicin, which would mimic cardiac dysfunction in CTRCD patients. After the oral administration of drugs (vehicle, SGLT2i, ARNI, Low-ARNI/SGLT2i, ARNI/SGLT2i), several physiologic parameters, including hemodynamic change, cardiac function, and histopathology, were evaluated. Bulk RNA-sequencing was performed to obtain insights into the molecular basis of a mouse heart response to Low-ARNI/SGLT2i treatment. For the first time, we report that the addition of low-dose ARNI with SGLT2i resulted in greater benefits than ARNI, SGLT2i alone or ARNI/SGLT2i combination in survival rate, cardiac function, hemodynamic change, and kidney function against doxorubicin-induced cardiotoxicity through peroxisome proliferator-activated receptor signaling pathway. Low-dose ARNI with SGLT2i combination treatment would be practically beneficial for improving cardiac functions against doxorubicin-induced heart failure with minimal adverse effects. Our findings suggest the Low-ARNI/SGLT2i combination as a feasible novel strategy in managing CTRCD patients.

Intracellular cholesterol transport inhibition Impairs autophagy flux by decreasing autophagosome-lysosome fusion.

BACKGROUND: Autophagy is an intracellular degradation process crucial for homeostasis. During autophagy, a double-membrane autophagosome fuses with lysosome through SNARE machinery STX17 to form autolysosome for degradation of damaged organelle. Whereas defective autophagy enhances cholesterol accumulation in the lysosome and impaired autophagic flux that results Niemann-Pick type C1 (NPC1) disease. However, exact interconnection between NPC1 and autophagic flux remain obscure due to the existence of controversial reports. RESULTS: This study aimed at a comparison of the effects of three autophagic inhibitor drugs, including chloroquine, U18666A, and bafilomycin A1, on the intracellular cholesterol transport and autophagy flux. Chloroquine, an autophagic flux inhibitor; U1866A, a NPC1 inhibitor, and bafilomycin A, a lysosomotropic agent are well known to inhibit autophagy by different mechanism. Here we showed that treatment with U1866A and bafilomycin A induces lysosomal cholesterol accumulation that prevented autophagic flux by decreasing autophagosome-lysosome fusion. We also demonstrated that accumulation of cholesterol within the lysosome did not affect lysosomal pH. Although the clearance of accumulated cholesterol by cyclodextrin restored the defective autophagosome-lysosome fusion, the autophagy flux restoration was possible only when lysosomal acidification was not altered. In addition, a failure of STX17 trafficking to autophagosomes plays a key role in prevention of autophagy flux caused by intracellular cholesterol transport inhibitors. CONCLUSIONS: Our data provide a new insight that the impaired autophagy flux does not necessarily result in lysosomal cholesterol accumulation even though it prevents autophagosome-lysosome fusion. Video abstract.

Single cell profiling of primary and paired metastatic lymph node tumors in breast cancer patients.

The microenvironment of lymph node metastasized tumors (LNMT) determines tumor progression and response to therapy, but a systematic study of LNMT is lacking. Here, we generate single-cell maps of primary tumors (PTs) and paired LNMTs in 8 breast cancer patients. We demonstrate that the activation, cytotoxicity, and proliferation of T cells are suppressed in LNMT compared with PT. CD4+CXCL13+ T cells in LNMT are more likely to differentiate into an exhausted state. Interestingly, LAMP3+ dendritic cells in LNMT display lower T cell priming and activating ability than in PT. Additionally, we identify a subtype of PLA2G2A+ cancer-associated fibroblasts enriched in HER2+ breast cancer patients that promotes immune infiltration. We also show that the antigen-presentation pathway is downregulated in malignant cells of the metastatic lymph node. Altogether, we characterize the microenvironment of LNMT and PT, which may shed light on the individualized therapeutic strategies for breast cancer patients with lymph node metastasis.

A "Flexible" Purely Organic Molecule Exhibiting Strong Spin-Orbital Coupling: Toward Nondoped Room-Temperature Phosphorescence OLEDs.

Purely organic materials usually exhibit weak spin-orbital coupling (SOC) effect because of the lack of noble heavy metals, and the generation and direct emission from the triplet state is spin-forbidden. This would lead to slow intersystem crossing, long triplet lifetime, and low phosphorescence quantum yield. Herein, strong spin-orbital coupling between singlet and triplet was observed in a "flexible" and twist thianthrene-pyrimidine-based purely organic compound in an amorphous film state, which shows a fast intersystem crossing process and a high phosphorescence rate of 1.1 × 103 s-1. The heavy atom sulfur and nitrogen atoms in the molecule can provide n-π* transition character for efficient spin-orbital coupling. Moreover, the flexible molecule skeleton enables conformational change and molecular vibration in excited states, which was proved to be vital for efficient vibrational spin-orbital coupling. Benefitting from the strong SOC effect, a nondoped purely organic phosphorescence light-emitting diode was fabricated, which achieves a maximum external quantum efficiency of 7.98%, corresponding to an exciton utilization ratio exceeding 87.6%.

Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (GC) (EBVaGC) is a distinct molecular subtype of GC with a favorable prognosis. However, the exact effects and potential mechanisms of EBV infection on immune checkpoint blockade (ICB) efficacy in GC remain to be clarified. Additionally, EBV-encoded RNA (EBER) in situ hybridization (ISH), the traditional method to detect EBV, could cause false-positive/false-negative results and not allow for characterizing other molecular biomarkers recommended by standard treatment guidelines for GC. Herein, we sought to investigate the efficacy and potential biomarkers of ICB in EBVaGC identified by next-generation sequencing (NGS). DESIGN: An NGS-based algorithm for detecting EBV was established and validated using two independent GC cohorts (124 in the training cohort and 76 in the validation cohort). The value of EBV infection for predicting ICB efficacy was evaluated among 95 patients with advanced or metastatic GC receiving ICB. The molecular predictive biomarkers for ICB efficacy were identified to improve the prediction accuracy of ICB efficacy in 22 patients with EBVaGC. RESULTS: Compared with orthogonal assay (EBER-ISH) results, the NGS-based algorithm achieved high performance with a sensitivity of 95.7% (22/23) and a specificity of 100% (53/53). EBV status was identified as an independent predictive factor for overall survival and progression-free survival in patients with DNA mismatch repair proficient (pMMR) GC following ICB. Moreover, the patients with EBV+/pMMR and EBV-/MMR deficient (dMMR) had comparable and favorable survival following ICB. Twenty-two patients with EBV+/pMMR achieved an objective response rate of 54.5% (12/22) on immunotherapy. Patients with EBVaGC with a high cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) level were less responsive to anti-programmed death-1/ligand 1 (PD-1/L1) monotherapy, and the combination of anti-CTLA-4 plus anti-PD-1/L1 checkpoint blockade benefited patients with EBVaGC more than anti-PD-1/L1 monotherapy with a trend close to significance (p=0.074). There were nearly significant differences in tumor mutational burden (TMB) level and SMARCA4 mutation frequency between the ICB response and non-response group. CONCLUSIONS: We developed an efficient NGS-based EBV detection strategy, and this strategy-identified EBV infection was as effective as dMMR in predicting ICB efficacy in GC. Additionally, we identified CTLA-4, TMB, and SMARCA4 mutation as potential predictive biomarkers of ICB efficacy in EBVaGC, which might better inform ICB treatment for EBVaGC.

Roles and Mechanisms of Deubiquitinases (DUBs) in Breast Cancer Progression and Targeted Drug Discovery.

Deubiquitinase (DUB) is an essential component in the ubiquitin-proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug targets. DUBs have shown significant roles in regulating breast cancer growth, metastasis, resistance to current therapies, and several canonical oncogenic signaling pathways. In addition, specific DUB inhibitors have been identified and are expected to benefit breast cancer patients in the future. Here, we review current knowledge about the effects and molecular mechanisms of DUBs in breast cancer, providing novel insight into treatments of breast cancer-targeting DUBs.

A Multiple Excited-State Engineering of Boron-Functionalized Diazapentacene Via a Tuning of the Molecular Orbital Coupling.

Harvesting high-energy excited-state energy is still challenging in organic chromophores. An introduction of boron atoms along the short axis of the diazapentacene backbone induces multiple emission characteristics. Our studies reveal that the weak molecular orbital (MO) coupling of the S3-S1 transition is responsible for the slow internal conversion rates. Such MO coupling-regulated anti-Kasha emission is different from the large band gap-induced anti-Kasha emission character of classical azulene derivatives. Theoretical studies reveal that a strong MO coupling of the S3-S0 transition is responsible for the higher photoluminescence quantum yield of the anti-Kasha emission in a more polar solution (tetrahydrofuran: 11%; cyclohexane: 0%). Such an MO coupling factor is generally overlooked in anti-Kasha emitters reported previously. Furthermore, the multiple emission can be regulated by solvent polarity, solvent temperature, and fluoride anion binding. As a proof of concept of harvesting high-energy emission, the multiple emission character has allowed us to design single-molecule white-light-emitting materials.

Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes.

Peroxisome abundance is regulated by homeostasis between the peroxisomal biogenesis and degradation processes. Peroxin 16 (PEX16) is a peroxisomal protein involved in trafficking membrane proteins for de novo peroxisome biogenesis. The present study demonstrates that PEX16 also modulates peroxisome abundance through pexophagic degradation. PEX16 knockdown in human retinal pigment epithelial-1 cells decreased peroxisome abundance and function, represented by reductions in the expression of peroxisome membrane protein ABCD3 and the levels of cholesterol and plasmalogens, respectively. The activation of pexophagy under PEX16 knockdown was shown by (i) abrogated peroxisome loss under PEX16 knockdown in autophagy-deficient ATG5 knockout cell lines, and (ii) increased autophagy flux and co-localization of p62-an autophagy adaptor protein-with ABCD3 in the presence of the autophagy inhibitor chloroquine. However, the levels of cholesterol and plasmalogens did not recover despite the restoration of peroxisome abundance following chloroquine treatment. Thus, PEX16 is indispensable for maintaining peroxisome homeostasis by regulating not only the commonly known biogenesis pathway but also the autophagic degradation of peroxisomes.

Trichomonas vaginalis infection impairs anion secretion in vaginal epithelium.

Trichomonas vaginalis is a common protozoan parasite, which causes trichomoniasis associated with severe adverse reproductive outcomes. However, the underlying pathogenesis has not been fully understood. As the first line of defense against invading pathogens, the vaginal epithelial cells are highly responsive to environmental stimuli and contribute to the formation of the optimal luminal fluid microenvironment. The cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel widely distributed at the apical membrane of epithelial cells, plays a crucial role in mediating the secretion of Cl- and HCO3-. In this study, we investigated the effect of T. vaginalis on vaginal epithelial ion transport elicited by prostaglandin E2 (PGE2), a major prostaglandin in the semen. Luminal administration of PGE2 triggered a remarkable and sustained increase of short-circuit current (ISC) in rat vaginal epithelium, which was mainly due to Cl- and HCO3- secretion mediated by the cAMP-activated CFTR. However, T. vaginalis infection significantly abrogated the ISC response evoked by PGE2, indicating impaired transepithelial anion transport via CFTR. Using a primary cell culture system of rat vaginal epithelium and a human vaginal epithelial cell line, we demonstrated that the expression of CFTR was significantly down-regulated after T. vaginalis infection. In addition, defective Cl- transport function of CFTR was observed in T. vaginalis-infected cells by measuring intracellular Cl- signals. Conclusively, T. vaginalis restrained exogenous PGE2-induced anion secretion through down-regulation of CFTR in vaginal epithelium. These results provide novel insights into the intervention of reproductive complications associated with T. vaginalis infection such as infertility and disequilibrium in vaginal fluid microenvironment.

Pharmacological inhibition of catalase induces peroxisome leakage and suppression of LPS induced inflammatory response in Raw 264.7 cell.

Peroxisomes are metabolically active organelles which are known to exert anti-inflammatory effects especially associated with the synthesis of mediators of inflammation resolution. However, the role of catalase and effects of peroxisome derived reactive oxygen species (ROS) caused by lipid peroxidation through 4-hydroxy-2-nonenal (4-HNE) on lipopolysaccharide (LPS) mediated inflammatory pathway are largely unknown. Here, we show that inhibition of catalase by 3-aminotriazole (3-AT) results in the generation of peroxisomal ROS, which contribute to leaky peroxisomes in RAW264.7 cells. Leaky peroxisomes cause the release of matrix proteins to the cytosol, which are degraded by ubiquitin proteasome system. Furthermore, 3-AT promotes the formation of 4HNE-IκBα adduct which directly interferes with LPS induced NF-κB activation. Even though, a selective degradation of peroxisome matrix proteins and formation of 4HNE- IκBα adduct are not directly related with each other, both of them are could be the consequences of lipid peroxidation occurring at the peroxisome membrane.

CBP-mediated Slug acetylation stabilizes Slug and promotes EMT and migration of breast cancer cells.

Slug, a member of the Snail family of transcriptional repressors, plays a key role in cancer progression, cellular plasticity, and epithelial to mesenchymal transition (EMT). Slug is a fast-turnover protein and its stability is controlled by post-translational modifications. Here, we identified that Slug is acetylated by acetyltransferase CREB-binding protein (CBP) in breast cancer cells. CBP directly interacts with the C-terminal domain of Slug through its catalytic histone acetyltransferase (HAT) domain, leading to acetylation of Slug at lysines 166 and 211. Analysis with acetylation-specific antibodies revealed that Slug is highly acetylated in metastatic breast cancer cells. Notably, Slug acetylation, mediated by CBP at lysines 166 and 211, doubles its half-life and increases its stability. Further, acetylated Slug downregulates the expression of E-cadherin, the epithelial marker, and upregulates the expression of N-cadherin and vimentin, thereby promoting breast cancer cell migration. In conclusion, the present study demonstrates that CBP-mediated Slug acetylation increases its stability, promoting EMT and migration of breast cancer cells.

New potential stable structures of XMg n (X = Ge, C, Sn; n = 2-12) clusters: XMg8 with high stability.

Several potential stable structures of X-doped magnesium (X = Ge, C, Sn) clusters have been fully investigated by using CALYPSO structure searching software together with density functional theory calculations. XMg n (X = Ge, C, Sn; n = 3-7) clusters have similar geometric structure grows in tetrahedron, while the structures of XMg n (X = Ge, C, Sn; n = 8-12) are based on a kind of tower-like geometry. Interestingly, the relative stability computations indicate that XMg8 (X = Ge, C, Sn) are more stable than other clusters, and thus can be identified as magic clusters. In addition, XMg8's (X = Ge, C, Sn) high stability and atomic interactions contained in structures are studied through their electronic localization function and molecular orbitals. It is shown that the covalent σ bond interaction of X-Mg and Mg-Mg are mainly responsible for their robust stability. Finally, the theoretical calculations of IR and Raman spectra of XMg8 (X = Ge, C, Sn) clusters were implemented for guiding further experimental observation.

Arming Anti-EGFRvIII CAR-T With TGFß Trap Improves Antitumor Efficacy in Glioma Mouse Models.

Glioblastoma (GBM) is an aggressive malignancy with poor prognosis. New therapeutic strategies for GBM are urgently needed. Although clinical studies have demonstrated the feasibility and safety of chimeric antigen receptor (CAR) T cell therapy for GBM, its efficacy has not been that impressive. The major limitation for anti-tumor efficacy of CAR-Ts is the immunosuppressive milieu of the GBM tumor microenvironment (TME). TGFß, a substantial component in GBM, compromises the immune response and contributes to immune evasion and tumor progression. To overcome this limitation and improve the efficacy of CAR-T cells for GBM, we optimized an EGFRvIII-specific CAR construct with TGFRII ectodomain as a TGFß-trap and generated TGFß-resistant CAR-Ts for GBM therapy. We demonstrated that this TGFß-trapped architecture enhanced anti-tumor efficacy of EGFRvIII-specific CAR-T and prolonged the survival of mice bearing GBM. In addition, the GBM-infiltrated microglia, typically considered tumorigenic, showed increased expression of M1 polarization markers after treatment with the TGFß-trap CAR-Ts group, indicating that these microglia were polarized toward a pro-inflammatory and anti-tumorigenic phenotype. Overall, these results indicated that arming CAR-T cells with a TGFß-trap diminishes the immunosuppressive effect and is a potential strategy to improve CAR-T efficacy for GBM therapy.

Four and a half LIM domains protein 1 can be as a double-edged sword in cancer progression.

Four and a half LIM domains protein 1 (FHL1), as the name suggests, contains four and a half LIM domains capable of interacting with various molecules, including structural proteins, kinases, and transcriptional machinery. FHL1 contains a zinc-finger domain and performs diverse roles in regulation of gene transcription, cytoarchitecture, cell proliferation, and signal transduction. Several studies have validated the importance of FHL1 in muscle development, myopathy, and cardiovascular diseases. Mutations in the FHL1 gene are associated with various myopathies. Recently, FHL1 was identified as a major host factor for chikungunya virus (CHIKV) infection in both humans and mice. Based on more recent findings over the last decade, FHL1 is proposed to play a dual role in cancer progression. On the one hand, FHL1 expression is suppressed in several cancer types, which correlates with increased metastatic disease and decreased survival. Moreover, FHL1 is reported to inhibit tumor cell growth and migration by associating with diverse signals, such as TGF-ß and ER, and therefore considered a tumor suppressor. On the other hand, FHL1 can function as an oncogenic protein that promotes tumor progression upon phosphorylation, reflecting complex roles in cancer. This review primarily focuses on the dual role and underlying mechanisms of action of FHL1 in human cancer progression and its clinical relevance.

An indigenous bacterium Bacillus XZM for phosphate enhanced transformation and migration of arsenate.

A number of arsenate-reducing bacteria respire adsorbed As(V), producing As(III) and thus contributing to arsenic mobilization from the solid phase to the aqueous phase. Two arsenate reducing genes, arsC and arrA, were both amplified in an indigenous bacterium Bacillus XZM isolated from high arsenic aquifer sediments. The effect of phosphate input on this novel bacterium in terms of mediating the biogeochemical behavior of arsenic was investigated for the first time. The results show bacterial growth and arsenate reduction appear to increase with the addition of phosphate. Input of 1 mM phosphate reduced the negative effects of As(V) on bacterial growth, resulting in 55-60% greater biomass production compared to lower phosphate inputs (0.01 and 0.1 mM). The data of real-time quantitative PCR (qPCR) indicated arsenate was involved in the expressions of two arsenate reductase genes (arsC and arrA genes) in indigenous bacterium Bacillus XZM. Overall, the addition of phosphate (from 0.1 to 1 mM) resulted in a doubling of arsenate bio-desorption from the sediment into the aqueous medium. Oxidation-reduction potential, as an environmental indicator of the bacterial reduction of metals, declined to -200 mV in the presence of strain XZM and 1 mM phosphate in the microcosm. Phosphate input enhanced arsenic biomigration, indicating the effect of phosphate concentration should be considered when studying the biogeochemical behavior of arsenic.