Latest insights into the epidemiology, characteristics, and therapeutic strategies of chronic hepatitis B patients in indeterminate phase.

As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of liver-related complications, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC with HBV infection has a significantly increased morbidity and mortality, whereas it could be preventable. The current goal of antiviral therapy for HBV infection is to decrease CHB-related morbidity and mortality, and achieve sustained suppression of virus replication, which is known as a functional or immunological cure. The natural history of chronic HBV infection includes four immune phases: the immune-tolerant phase, immune-active phase, inactive phase, and reactivation phase. However, many CHB patients do not fit into any of these defined phases and are regarded as indeterminate. A large proportion of indeterminate patients are only treated with dynamic monitoring rather than recommended antiviral therapy, mainly due to the lack of definite guidelines. However, many of these patients may gradually have significant liver histopathological changes during disease progression. Recent studies have focused on the prevalence, progression, and carcinogenicity of indeterminate CHB, and more attention has been given to the prevention, detection, and treatment for these patients. Herein, we discuss the latest understanding of the epidemiology, clinical characteristics, and therapeutic strategies of indeterminate CHB, to provide avenues for the management of these patients.

Biochar modulates intracellular electron transfer for nitrate reduction in denitrifying anaerobic methane oxidizing archaea.

Denitrifying anaerobic methane oxidizing (DAMO) archaea plays a significant role in simultaneously nitrogen removal and methane mitigation, yet its limited metabolic activity hinders engineering applications. This study employed biochar to explore its potential for enhancing the metabolic activity and nitrate reduction capacity of DAMO microorganisms. Sawdust biochar (7 g/L) was found to increase the nitrate reduction rate by 2.85 times, although it did not affect the nitrite reduction rate individually. Scanning electron microscopy (SEM) and fluorescence excitation-emission matrix (EEM) analyses revealed that biochar promoted microbial aggregation, and stimulated the secretion of extracellular polymeric substances (EPS). Moreover, biochar bolstered the redox capacity and conductivity of the biofilm, notably enhancing the activity of the electron transfer system by 1.65 times. Key genes involved in intracellular electron transport (Hdr, MHC, Rnf) and membrane transport proteins (BBP, ABC, NDH) of archaea were significantly up-regulated. These findings suggest that biochar regulates electrons generated by reverse methanogenesis to the membrane for nitrate reduction.

Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma.

As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.

Achieving Long-Term Stability of Partial Nitrification and Autotrophic Denitrification in an MABR via Sulfide Dosing.

While partial nitrification (PN) has the potential to reduce energy for aeration, it has proven to be unstable when treating low-strength wastewater. This study introduces an innovative combined strategy incorporating a low rate of oxygen supply, pH control, and sulfide addition to selectively inhibit nitrite-oxidizing bacteria (NOB). This strategy led to a stable PN in a laboratory-scale membrane aerated biofilm reactor (MABR). Over a period of 260 days, the nitrite accumulation ratio exceeded 60% when treating synthetic sewage containing 50 mg NH4+-N/L. Through in situ activity testing and high-throughput sequencing, the combined strategy led to low levels of nitrite-oxidation activity (<5.5 mg N/m2 h), Nitrospira species (relative abundance <1%), and transcription of nitrite-oxidation genes (undetectable). The addition of sulfide led to simultaneous PN and autotrophic denitrification in the single-stage MABR, resulting in over 60% total inorganic nitrogen removal. Sulfur-based autotrophic denitrification consumed nitrite and inhibited NOB conversion of nitrite to nitrate. The combined strategy has potential to be applied in large-scale sewage treatment and deserves further exploration.

Long Noncoding RNAs in Response to Hyperosmolarity Stress, but Not Salt Stress, Were Mainly Enriched in the Rice Roots.

Due to their immobility and possession of underground parts, plants have evolved various mechanisms to endure and adapt to abiotic stresses such as extreme temperatures, drought, and salinity. However, the contribution of long noncoding RNAs (lncRNAs) to different abiotic stresses and distinct rice seedling parts remains largely uncharacterized beyond the protein-coding gene (PCG) layer. Using transcriptomics and bioinformatics methods, we systematically identified lncRNAs and characterized their expression patterns in the roots and shoots of wild type (WT) and ososca1.1 (reduced hyperosmolality-induced [Ca2+]i increase in rice) seedlings under hyperosmolarity and salt stresses. Here, 2937 candidate lncRNAs were identified in rice seedlings, with intergenic lncRNAs representing the largest category. Although the detectable sequence conservation of lncRNAs was low, we observed that lncRNAs had more orthologs within the Oryza. By comparing WT and ososca1.1, the transcription level of OsOSCA1.1-related lncRNAs in roots was greatly enhanced in the face of hyperosmolality stress. Regarding regulation mode, the co-expression network revealed connections between trans-regulated lncRNAs and their target PCGs related to OsOSCA1.1 and its mediation of hyperosmolality stress sensing. Interestingly, compared to PCGs, the expression of lncRNAs in roots was more sensitive to hyperosmolarity stress than to salt stress. Furthermore, OsOSCA1.1-related hyperosmolarity stress-responsive lncRNAs were enriched in roots, and their potential cis-regulated genes were associated with transcriptional regulation and signaling transduction. Not to be ignored, we identified a motif-conserved and hyperosmolarity stress-activated lncRNA gene (OSlncRNA), speculating on its origin and evolutionary history in Oryza. In summary, we provide a global perspective and a lncRNA resource to understand hyperosmolality stress sensing in rice roots, which helps to decode the complex molecular networks involved in plant sensing and adaptation to stressful environments.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer.

As a highly invasive malignancy, esophageal cancer (EC) is a global health issue, and was the eighth most prevalent cancer and the sixth leading cause of cancer-related death worldwide in 2020. Due to its highly immunogenic nature, emer-ging immunotherapy approaches, such as immune checkpoint blockade, have demonstrated promising efficacy in treating EC; however, certain limitations and challenges still exist. In addition, tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment (TIME); thus, understanding the TIME is urgent and crucial, especially given the im-portance of an immunosuppressive microenvironment in tumor progression. The aim of this review was to better elucidate the mechanisms of the suppressive TIME, including cell infiltration, immune cell subsets, cytokines and signaling pathways in the tumor microenvironment of EC patients, as well as the downregulated expression of major histocompatibility complex molecules in tumor cells, to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies. Therefore, personalized treatments could be developed to maximize the advantages of immunotherapy.

Influence of microbial inoculation site on trichloroethylene degradation in electrokinetic-enhanced bioremediation of low-permeability soils.

The integration of electrokinetic and bioremediation (EK-BIO) represents an innovative approach for addressing trichloroethylene (TCE) contamination in low-permeability soil. However, there remains a knowledge gap in the impact of the inoculation approach on TCE dechlorination and the microbial response with the presence of co-existing substances. In this study, four 1-dimensional columns were constructed with different inoculation treatments. Monitoring the operation conditions revealed that a stabilization period (∼40 days) was required to reduce voltage fluctuation. The group with inoculation into the soil middle (Group B) exhibited the highest TCE dechlorination efficiency, achieving a TCE removal rate of 84%, which was 1.1-3.2 fold higher compared to the others. Among degraded products in Group B, 39% was ethylene. The physicochemical properties of the post-soil at different regions illustrated that dechlorination coincided with the Fe(III) and SO42- reduction, meaning that the EK-BIO system promoted the formation of a reducing environment. Microbial community analysis demonstrated that Dehalococcoides was only detected in the treatment of injection at soil middle or near the cathode, with abundance enriched by 2.1%-7.2%. The principal components analysis indicated that the inoculation approach significantly affected the evolution of functional bacteria. Quantitative polymerase chain reaction (qPCR) analysis demonstrated that Group B exhibited at least 2.8 and 4.2-fold higher copies of functional genes (tceA, vcrA) than those of other groups. In conclusion, this study contributes to the development of effective strategies for enhancing TCE biodechlorination in the EK-BIO system, which is particularly beneficial for the remediation of low-permeability soils.

Efficient perchlorate reduction in microaerobic environment facilitated by partner methane oxidizers.

The conventional perchlorate (ClO4-) reduction typically necessitates anaerobic conditions. However, in this study, we observed efficient ClO4- reduction using CH4 as the electron donor in a microaerobic environment. The maximum ClO4- removal flux of 2.18 g/m2·d was achieved in CH4-based biofilm. The kinetics of ClO4- reduction showed significant differences, with trace oxygen increasing the reduction rate of ClO4-, whereas oxygen levels exceeding 2 mg/L decelerated the ClO4- reduction. In the absence of exogenous oxygen, anaerobic methanotrophic (ANME) archaea contribute more than 80% electrons through the reverse methanogenesis pathway for ClO4- reduction. Simultaneously, microorganisms activate CH4 by utilizing oxygen generated from chlorite (ClO2-) disproportionation. In the presence of exogenous oxygen, methane oxidizers predominantly consume oxygen to drive the aerobic oxidation of methane. It is indicated that methane oxidizers and perchlorate reducing bacteria can form aggregates to resist external oxygen shocks and achieve efficient ClO4- reduction under microaerobic condition. These findings provide new insights into biological CH4 mitigation and ClO4- removal in hypoxic environment.

Enzyme-induced reactive oxygen species trigger oxidative degradation of sulfamethoxazole within a methanotrophic biofilm.

Although microorganisms carrying copper-containing membrane-bound monooxygenase (CuMMOs), such as particulate methane monooxygenase (pMMO) and ammonia monooxygenase (AMO), have been extensively documented for their capability to degrade organic micropollutants (OMPs), the underlying reactive mechanism remains elusive. In this study, we for the first time demonstrate biogenic reactive oxygen species (ROS) play important roles in the degradation of sulfamethoxazole (SMX), a representative OMP, within a methane-fed biofilm. Highly-efficient and consistent SMX biodegradation was achieved in a CH4-based membrane biofilm reactor (MBfR), manifesting a remarkable SMX removal rate of 1210.6 ± 39.0 µg·L-1·d-1. Enzyme inhibition and ROS clearance experiments confirmed the significant contribution of ROS, which were generated through the catalytic reaction of pMMO and AMO enzymes, in facilitating SMX degradation. Through a combination of density functional theory (DFT) calculations, electron paramagnetic resonance (EPR) analysis, and transformation product detection, we elucidated that the ROS primarily targeted the aniline group in the SMX molecule, inducing the formation of aromatic radicals and its progressive mineralization. In contrast, the isoxazole-ring was not susceptible to electrophilic ROS attacks, leading to accumulation of 3-amino-5-methylisoxazole (3A5MI). Furthermore, microbiological analysis suggested Methylosarcina (a methanotroph) and Candidatus Nitrosotenuis (an ammonia-oxidizing archaea) collaborated as the SMX degraders, who carried highly conserved and expressed CuMMOs (pMMO and AMO) for ROS generation, thereby triggering the oxidative degradation of SMX. This study deciphers SMX biodegradation through a fresh perspective of free radical chemistry, and concurrently providing a theoretical framework for the advancement of environmental biotechnologies aimed at OMP removal.

Electrokinetic bioremediation of trichloroethylene and Cr/As co-contaminated soils with elevated sulfate.

Co-contaminants and complex subsurface conditions pose great challenges to site remediation. This study demonstrates the potential of electrokinetic bioremediation (EK-BIO) in treating co-contaminants of chlorinated solvents and heavy metals in low-permeability soils with elevated sulfate. EK-BIO columns were filled with field soils, and were fed by the electrolyte containing 20 mg/L trichloroethylene (TCE), 250 µM Cr(VI), 25 µM As(III), 10 mM lactate, and 10 mM sulfate. A dechlorinating consortium containing Dehalococcoides (Dhc) was injected several times during a 199-d treatment at ∼1 V/cm. Sulfate reduction, Cr/As immobilization, and complete TCE biodechlorination were observed sequentially. EK-BIO facilitated the delivery of lactate, Cr(VI)/As(III), and sulfate to the soils, creating favorable reductive conditions for contaminant removal. Supplementary batch experiments and metagenomic/transcriptomic analysis suggested that sulfate promoted the reductive immobilization of Cr(VI) by generating sulfide species, which subsequently enhanced TCE biodechlorination by alleviating Cr(VI) toxicity. The dechlorinating community displayed a high As(III) tolerance. Metagenomic binning analysis revealed the dechlorinating activity of Dhc and the potential synergistic effects from other bacteria in mitigating heavy metal toxicity. This study justified the feasibility of EK-BIO for co-contaminant treatment and provided mechanistic insights into EK-BIO treatment.

Unveiling the inhibitory mechanisms of chromium exposure on microbial reductive dechlorination: Kinetics and microbial responses.

Chromium and organochlorine solvents, particularly trichloroethene (TCE), are pervasive co-existing contaminants in subsurface aquifers due to their extensive industrial use and improper disposal practices. In this study, we investigated the microbial dechlorination kinetics under different TCE-Cr(Ⅲ/VI) composite pollution conditions and elucidated microbial response mechanisms based on community shift patterns and metagenomic analysis. Our results revealed that the reductive dechlorinating consortium had high resistance to Cr(III) but extreme sensitivity to Cr(VI) disturbance, resulting in a persistent inhibitory effect on subsequent dechlorination. Interestingly, the vinyl chloride-respiring organohalide-respiring bacteria (OHRB) was notably more susceptible to Cr(III/VI) exposure than the trichloroethene-respiring one, possibly due to inferior competition for growth substrates, such as electron donors. In terms of synergistic non-OHRB populations, Cr(III/VI) exposure had limited impacts on lactate fermentation but significantly interfered with H2-producing acetogenesis, leading to inhibited microbial dechlorination due to electron donor deficiencies. However, this inhibition can be effectively mitigated by the amendment of exogenous H2 supply. Furthermore, being the predominant OHRB, Dehalococcoides have inherent Cr(VI) resistance defects and collaborate with synergistic non-OHRB populations to achieve concurrent bio-detoxication of Cr(VI) and TCE. Our findings expand the understanding of the response patterns of different functional populations towards Cr(III/VI) stress, and provide valuable insights for the development of in situ bioremediation strategies for sites co-contaminated with chloroethene and chromium.

Factors associated with immunological non-response after ART initiation: a retrospective observational cohort study.

BACKGROUND: Among people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented. METHODS: We obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/µl after 24 months' treatment), immunological incomplete responders (ICRs) (200-350 cells/µl) and INRs (< 200 cells/µl). Multivariable logistic regression was used to assess factors associated with immunological non-response. RESULTS: A total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39-3.09), older age [40-49 years (vs. 18-29 years): 2.05, 1.29-3.25; 50-59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84-10.67], HBV co-infection (1.63, 1.14-2.34), HCV co-infection (2.01, 1.01-4.02), lower CD4 + T cell count [50-200 cells/µl (vs. 200-350 cells/µl): 40.20, 16.83-96.01; < 50 cells/µl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98-4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26-0.82). CONCLUSIONS: We found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor.

Complete degradation of di-n-butyl phthalate by Glutamicibacter sp. strain 0426 with a novel pathway.

Di-n-butyl phthalate (DBP) is widely used as plasticizer that has potential carcinogenic, teratogenic, and endocrine effects. In the present study, an efficient DBP-degrading bacterial strain 0426 was isolated and identified as a Glutamicibacter sp. strain 0426. It can utilize DBP as the sole source of carbon and energy and completely degraded 300 mg/L of DBP within 12 h. The optimal conditions (pH 6.9 and 31.7 °C) for DBP degradation were determined by response surface methodology and DBP degradation well fitted with the first-order kinetics. Bioaugmentation of contaminated soil with strain 0426 enhanced DBP (1 mg/g soil) degradation, indicating the application potential of strain 0426 for environment DBP removal. Strain 0426 harbors a distinctive DBP hydrolysis mechanism with two parallel benzoate metabolic pathways, which may account for the remarkable performance of DBP degradation. Sequences alignment has shown that an alpha/beta fold hydrolase (WP_083586847.1) contained a conserved catalytic triad and pentapeptide motif (GX1SX2G), of which function is similar to phthalic acid ester (PAEs) hydrolases and lipases that can efficiently catalyze hydrolysis of water-insoluble substrates. Furthermore, phthalic acid was converted to benzoate by decarboxylation, which entered into two different pathways: one is the protocatechuic acid pathway under the role of pca cluster, and the other is the catechol pathway. This study demonstrates a novel DBP degradation pathway, which broadens our understanding of the mechanisms of PAE biodegradation.

CCCTC-binding factor: the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 that upregulates the sialylation of anti-citrullinated protein antibodies in rheumatoid arthritis.

OBJECTIVE: Sialylation of the crystallizable fragment (Fc) of ACPAs, which is catalysed by ß-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) could attenuate inflammation of RA. In this study, we screened the transcription factor of ST6GAL1 and elucidated the mechanism of transcriptionally upregulating sialylation of ACPAs in B cells to explore its role in the progression of RA. METHODS: Transcription factors interacting with the P2 promoter of ST6GAL1 were screened by DNA pull-down and liquid chromatography with tandem mass spectrometry (LC-MS/MS), and verified by chromatin immunoprecipitation (ChIP), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The function of the CCCTC-binding factor (CTCF) on the expression of ST6GAL1 and the inflammatory effect of ACPAs were verified by knocking down and overexpressing CTCF in B cells. The CIA model was constructed from B cell-specific CTCF knockout mice to explore the effect of CTCF on arthritis progression. RESULTS: We observed that the levels of ST6GAL1 and ACPAs sialylation decreased in the serum of RA patients and were negatively correlated with DAS28 scores. Subsequently, CTCF was screened and verified as the transcription factor interacting with the P2 promoter of ST6GAL1, which enhances the sialylation of ACPAs, thus weakening the inflammatory activity of ACPAs. Furthermore, the above results were also verified in the CIA model constructed from B cell-specific CTCF knockout mice. CONCLUSION: CCCTC-binding factor is the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 in B cells that upregulates the sialylation of ACPAs in RA and attenuates the disease progression.

Synthetic Nuclease-Producing Microbiome Achieves Efficient Removal of Extracellular Antibiotic Resistance Genes from Wastewater Effluent.

Antibiotic resistance gene (ARG) transmission poses significant threats to human health. The effluent of wastewater treatment plants is demonstrated as a hotspot source of ARGs released into the environment. In this study, a synthetic microbiome containing nuclease-producing Deinococcus radiodurans was constructed to remove extracellular ARGs. Results of quantitative polymerase chain reaction (qPCR) showed significant reduction in plasmid RP4-associated ARGs (by more than 3 orders of magnitude) and reduction of indigenous ARG sul1 and mobile genetic element (MGE) intl1 (by more than 1 order of magnitude) in the synthetic microbiome compared to the control without D. radiodurans. Metagenomic analysis revealed a decrease in ARG and MGE diversity in extracellular DNA (eDNA) of the treated group. Notably, whereas eight antibiotic-resistant plasmids with mobility risk were detected in the control, only one was detected in the synthetic microbiome. The abundance of the nuclease encoding gene exeM, quantified by qPCR, indicated its enrichment in the synthetic microbiome, which ensures stable eDNA degradation even when D. radiodurans decreased. Moreover, intracellular ARGs and MGEs and pathogenic ARG hosts in the river receiving treated effluent were lower than those in the river receiving untreated effluent. Overall, this study presents a new approach for removing extracellular ARGs and further reducing the risk of ARG transmission in receiving rivers.

Mechanism Underlying Bacillus subtilis BS-Z15 Metabolite-Induced Prevention of Grain Contamination by Aspergillus flavus.

Aspergillus flavus can cause mildew in corn, peanuts, and other foods as well as animal feed, which seriously endangers human and livestock health; thus, preventing A. flavus contamination is imperative. Previous studies have found that the secondary metabolites of Bacillus subtilis BS-Z15 have broad-spectrum-inhibiting fungal activity, further confirming that the main active inhibiting fungal substance is Mycosubtilin (Myco). In this paper, corn and peanuts were treated with 0, 100, and 200 µg/mL BS-Z15 secondary metabolites (BS-Z15-SMA) for 7 days, and the aflatoxin contamination prevention effect was examined. The results showed that with increasing BS-Z15-SMA concentration, the aflatoxin contamination prevention effect was significantly enhanced. The above toxicity phenomena became more significant with extended BS-Z15-SMA treatment time. Scanning electron microscopy showed that 4 µg/mL Myco treatment resulted in a dented A. flavus surface and breakage of both the conidial stem and the mycelium. Transcriptome results showed that Myco significantly affected gene expression in A. flavus spores. The downregulated genes were significantly enriched in cell wall synthesis, transcription and translation, transmembrane transport pathways, and pathways related to key enzymes for aflatoxin synthesis. These results suggest that Myco could be used as a new bioactive material to prevent aflatoxin synthesis and contamination.

The Secondary Metabolites of Bacillus subtilis Strain Z15 Induce Apoptosis in Hepatocellular Carcinoma Cells.

The lipopeptides produced by Bacillus subtilis have anti-cancer potential. We had previously identified a secondary metabolite of B. subtilis strain Z15 (BS-Z15), which has an operon that regulates lipopeptide synthesis, and also demonstrated that the fermentation products of this strain exerted antioxidant and pro-immune effects. The purpose of this study was to investigate in vitro and in vivo the anticancer effects of BS-Z15 secondary metabolites (BS-Z15 SMs) on hepatocellular carcinoma (HCC) cells. BS-Z15 SMs significantly inhibited H22 cell-derived murine xenograft tumor growth without any systemic toxicity. In addition, BS-Z15 SMs decreased the viability of H22 cells and BEL-7404 cells in vitro with respective IC50 values of 33.83 and 27.26 µg/mL. Consistent with this, BS-Z15 SMs induced apoptosis and G0/G1 phase arrest in the BEL-7404 cells, and the mitochondrial membrane potential was also significantly reduced in a dose-dependent manner. Mechanistically, BS-Z15 SMs upregulated the pro-apoptotic p53, Bax, cytochrome C, and cleaved-caspase-3/9 proteins and downregulated the anti-apoptotic Bcl-2. These findings suggest that the induction of apoptosis in HCC cells by BS-Z15 SMs may be related to the mitochondrial pathway. Thus, the secondary metabolites of B. subtilis strain Z15 are promising to become new anti-cancer drugs for the clinical treatment of liver cancer.

Simultaneous antibiotic removal and mitigation of resistance induction by manganese bio-oxidation process.

Microbial degradation to remove residual antibiotics in wastewater is of growing interest. However, biological treatment of antibiotics may cause resistance dissemination by mutations and horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs). In this study, a Mn(Ⅱ)-oxidizing bacterium (MnOB), Pseudomonas aeruginosa MQ2, simultaneously degraded antibiotics, decreased HGT, and mitigated antibiotic resistance mutation. Intracellular Mn(II) levels increased during manganese oxidation, and biogenic manganese oxides (BioMnOx, including Mn(II), Mn(III) and Mn(IV)) tightly coated the cell surface. Mn(II) bio-oxidation mitigated antibiotic resistance acquisition from an E. coli ARG donor and mitigated antibiotic resistance inducement by decreasing conjugative transfer and mutation, respectively. BioMnOx also oxidized ciprofloxacin (1 mg/L) and tetracycline (5 mg/L), respectively removing 93% and 96% within 24 h. Transcriptomic analysis revealed that two new multicopper oxidase and one peroxidase genes are involved in Mn(II) oxidation. Downregulation of SOS response, multidrug resistance and type Ⅳ secretion system related genes explained that Mn(II) and BioMnOx decreased HGT and mitigated resistance mutation by alleviating oxidative stress, which makes recipient cells more vulnerable to ARG acquisition and mutation. A manganese bio-oxidation based reactor was constructed and completely removed tetracycline with environmental concentration within 4-hour hydraulic retention time. Overall, this study suggests that Mn (II) bio-oxidation process could be exploited to control antibiotic contamination and mitigate resistance propagation during water treatment.

Novel Sulfate Reduction Coupled to Simultaneous Nitrification and Autotrophic Denitrification Process for Removing Nitrogen and Organics from Saline Wastewater.

Highly efficient sulfate reduction coupled to autotrophic denitrification plus nitrification is demonstrated by integrating an anaerobic membrane bioreactor (AnMBR) with a membrane aerated biofilm reactor (MABR). Concurrent chemical oxygen demand (COD) removal and sulfate reduction were accomplished in the AnMBR, while simultaneous nitrification and autotrophic denitrification were carried out in the MABR. Separate operation of the MABR achieved >90% total nitrogen (TN) removal when the N/S ratio was controlled at 0.4 gN/gS. The integrated AnMBR-MABR system efficiently resisted influent variability, realizing >95% COD removal in the AnMBR and >75% TN removal in the MABR when the influent COD/N ratio was above 4 gCOD/gN. Membrane fouling did not happen during ∼170 days of operation. Due to sulfide oxidation, a large amount of elemental sulfur (S0) accumulated in the MABR biofilm, where it served as an electron donor for denitrification. Microbial community analysis indicated that Nitrospira and Thiobacillus played key roles in nitrification and sulfide-driven denitrification, respectively, and that they occurred in different layers of the biofilm. This novel process offers advantages of a small land-area footprint, modular operation, and high efficiency electron-donor and oxygen utilizations, particularly for wastewater with a low COD/N ratio.