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Jing Zhang,1,* Xizhen Han,1,* Xiang Li,2 Yun Luo,1 Haiping Zhao,1 Ming Yang,1 Bin Ni,1 Zhenggen Liao11Key Laboratory of Modern Preparation of TCM, Ministry of Education, 2National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China*These authors contributed equally to this workPurpose: Novel panax notoginsenoside-loaded core-shell hybrid liposomal vesicles (PNS-HLV) were developed to resolve the restricted bioavailability of PNS and to enhance its protective effects in vivo on oral administration.Methods: Physicochemical characterizations of PNS-HLV included assessment of morphology, particle size and zeta potential, encapsulation efficiency (EE%), stability and in vitro release study. In addition, to evaluate its oral treatment potential, we compared the effect of PNS-HLV on global cerebral ischemia/reperfusion and acute myocardial ischemia injury with those of PNS solution, conventional PNS-loaded nanoparticles, and liposomes.Results: In comparison with PNS solution, conventional PNS-loaded nanoparticles and liposomes, PNS-HLV was stable for at least 12 months at 4°C. Satisfactory improvements in the EE% of notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were shown with the differences in EE% shortened and the greater controlled drug release profiles were exhibited from PNS-HLV. The improvements in the physicochemical properties of HLV contributed to the results that PNS-HLV was able to significantly inhibit the edema of brain and reduce the infarct volume, while it could markedly inhibit H2O2, modified Dixon agar, and serum lactate dehydrogenase, and increase superoxide dismutase (P < 0.05).Conclusion: The results of the present study imply that HLV has promising prospects for improving free drug bioactivity on oral administration.Keywords: liposomes, nanoparticles, panax notoginsenoside, physicochemical properties, in vivo animal models

There are discrepancy between MR findings and clinical presentations. The compressed cervical cord in patients of the spondylotic myelopathy may be normal on conventional MRI when it is at the earlier stage or even if patients had severe symptoms. Therefore, it is necessary to take a developed MR technique--diffusion tensor imaging (DTI)--to detect the intramedullary lesions. Prospective MR and DTI were performed in 53 patients with cervical compressive myelopathy and twenty healthy volunteers. DTI was performed along six non-collinear directions with single-shot spin echo echo-planar imaging (EPI) sequence. Intramedullary apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in four segments (C2/3, C3/4, C4/5, C5/6) for volunteers, in lesions (or the compressed cord) and normal cord for patients. DTI original images were processed to produce color DTI maps. In the volunteers' group, cervical cord exhibited blue on the color DTI map. FA values between four segments had a significant difference (P < 0.01), with the highest FA value (0.85 ± 0.03) at C2/3 level. However, ADC value between them had no significant difference (P > 0.05). For patients, only 24 cases showed hyperintense on T2-weighted image, while 39 cases shown patchy green signal on color DTI maps. ADC and FA values between lesions or the compressed cord and normal spinal cord of patients had a significant difference (both P < 0.01). FA value at C2/3 cord is the highest of other segments and it gradually decreases towards the caudal direction. Using single-shot spin echo EPI sequence and six non-collinear diffusion directions with b value of 400 s mm(-2), DTI can clearly show the intramedullary microstructure and more lesions than conventional MRI. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 NH 4 + -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/m 2 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.

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 SO 4 2- 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The incorporation of conductive materials to enhance electron transfer in bioelectrochemical systems (BES) is considered a promising approach. However, the specific effects and mechanisms of these materials on trichloroethylene (TCE) reductive dechlorination in BES remains are not fully understood. This study investigated the use of magnetite nanoparticles (MNP) and biochars (BC) as coatings on biocathodes for TCE reduction. Results demonstrated that the average dechlorination rates of MNP-Biocathode (122.89 μM Cl·d -1 ) and BC-Biocathode (102.88 μM Cl·d -1 ) were greatly higher than that of Biocathode (78.17 μM Cl·d -1 ). Based on MATLAB calculation, the dechlorination rate exhibited a more significantly increase in TCE-to-DCE step than the other dechlorination steps. Microbial community analyses revealed an increase in the relative abundance of electroactive and dechlorinating populations (e.g., Pseudomonas, Geobacter, and Desulfovibrio) in MNP-Biocathode and BC-Biocathode. Functional gene analysis via RT-qPCR showed the expression of dehalogenase (RDase) and direct electron transfer (DET) related genes was upregulated with the addition of MNP and BC. These findings suggest that conductive materials might accelerate reductive dechlorination by enhancing DET. The difference of physicochemical characteristics (e.g. particle size and specific surface area), electron transfer enhancement mechanism between MNP and BC as well as the reduction of Fe(III) by hydrogen may explain the superior dechlorination rate observed with MNP-Biocathode., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 H 2 -producing acetogenesis, leading to inhibited microbial dechlorination due to electron donor deficiencies. However, this inhibition can be effectively mitigated by the amendment of exogenous H 2 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 CH 4 -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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Doxorubicin has been used extensively as a potent anticancer agent, but its clinical use is limited by its cardiotoxicity. However, the underlying mechanisms remain to be fully elucidated. In this study, we tested whether NADPH oxidase 2 (Nox2) mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced heart failure. Nox2 knockout (KO) and wild-type (WT) mice were randomly assigned to receive a single injection of doxorubicin (15 mg/kg, i.p.) or saline. WT doxorubicin mice exhibited the decreases in survival rate, left ventricular (LV) wall thickness and LV fractional shortening and the increase in the lung wet-to-dry weight ratio 1 week after the injections. These alterations were attenuated in Nox2 KO doxorubicin mice. In WT doxorubicin mice, myocardial oxidative stress was increased, myocardial noradrenergic nerve fibers were reduced, myocardial expression of PGP9.5, GAP43, tyrosine hydroxylase and norepinephrine transporter was decreased, and these changes were prevented in Nox2 KO doxorubicin mice. Myocyte autophagy was increased and myocyte size was decreased in WT doxorubicin mice, but not in Nox2 KO doxorubicin mice. Nox2 mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy-both of which contribute to cardiac atrophy and failure after doxorubicin treatment., (© 2024. The Author(s).)

Doxorubicin is widely used for the treatment of human cancer, but its clinical use is limited by a cumulative dose-dependent cardiotoxicity. However, the mechanism of doxorubicin-induced cardiac atrophy and failure remains to be fully understood. In this study, we tested whether the specific NADPH oxidase 2 (Nox2) inhibitor GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, leading to the amelioration of cardiac atrophy and dysfunction in chronic doxorubicin-induced cardiomyopathy. Mice were randomized to receive saline, doxorubicin (2.5 mg/kg, every other day, 6 times) or doxorubicin plus GSK2795039 (2.5 mg/kg, twice a day, 9 weeks). Left ventricular (LV) total wall thickness and LV ejection fraction were decreased in doxorubicin-treated mice compared with saline-treated mice and the decreases were prevented by the treatment of the specific Nox2 inhibitor GSK2795039. The ratio of total heart weight to tibia length and myocyte cross-sectional area were decreased in doxorubicin-treated mice, and the decreases were attenuated by the GSK2795039 treatment. In doxorubicin-treated mice, myocardial Nox2 and 4-hydroxynonenal levels were increased, myocardial expression of GAP43, tyrosine hydroxylase and norepinephrine transporter, markers of sympathetic nerve terminals, was decreased, and these changes were prevented by the GSK2795039 treatment. The ratio of LC3 II/I, a marker of autophagy, and Atg5, Atg12 and Atg12-Atg5 conjugate proteins were increased in doxorubicin-treated mice, and the increases were attenuated by the GSK2795039 treatment. These findings suggest that inhibition of Nox2 by GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, thereby ameliorating cardiac atrophy and dysfunction after chronic doxorubicin treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The conventional perchlorate (ClO 4 - ) reduction typically necessitates anaerobic conditions. However, in this study, we observed efficient ClO 4 - reduction using CH 4 as the electron donor in a microaerobic environment. The maximum ClO 4 - removal flux of 2.18 g/m 2 ·d was achieved in CH 4 -based biofilm. The kinetics of ClO 4 - reduction showed significant differences, with trace oxygen increasing the reduction rate of ClO 4 - , whereas oxygen levels exceeding 2 mg/L decelerated the ClO 4 - reduction. In the absence of exogenous oxygen, anaerobic methanotrophic (ANME) archaea contribute more than 80% electrons through the reverse methanogenesis pathway for ClO 4 - reduction. Simultaneously, microorganisms activate CH 4 by utilizing oxygen generated from chlorite (ClO 2 - ) 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 ClO 4 - reduction under microaerobic condition. These findings provide new insights into biological CH 4 mitigation and ClO 4 - removal in hypoxic environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To explore the neuroprotective effects of ARA290 and the role of β-common receptor (βCR) in a mouse model of middle cerebral artery occlusion (MCAO)., Methods: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO-induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5-triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry-based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and βCR were measured by western blot., Results: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against βCR., Conclusion: ARA290 provided a neuroprotective effect via βCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

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&#95;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., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Different gradients of dissolved oxygen (DO) regulate the microbial community and nitrogen removal pathways of denitrifying anaerobic methane oxidation (DAMO) and anaerobic ammonium oxidation (Anammox) coupled process in a batch biofilm reactor. Under completely anaerobic condition, approximately 72 mg NO 3 - -N/L was removed at a daily rate of 6.55 mg N/L, whereas a peak accumulation of 95 mg NO 3 - -N/L was observed during DO reached 0.5 mg/L. There is a decrease in the abundance of Candidatus Methylomirabilis (24.1%), Candidatus Methanoperedens (23.3%), and Candidatus Kuenenia (22.6%) to below 5% when DO levels reached 0.2 mg/L. Moreover, key genes associated with the reverse methanogenesis (mcrA) and anaerobic ammonium oxidase (hzo) decreased. These findings indicate that during oxygen shock, methanotrophs and denitrifiers replace Anammox bacteria on the outer sphere of the biofilm, whereas DAMO bacteria and archaea are protected from external oxygen shock due to the microbial stratification of biofilm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.

Inorganic arsenic and organochlorines are frequently co-occurring contaminants in anoxic groundwater environments, and the bioremediation of their composite pollution has long been a rigorous predicament. Currently, the dechlorination behaviors and stress responses of microbial dechlorination consortia to arsenic are not yet fully understood. This study assessed the reductive dechlorination performance of a Dehalococcoides-bearing microcosm DH under gradient concentrations of arsenate [As(V)] or arsenite [As(III)] and investigated the response patterns of different functional microorganisms. Our results demonstrated that although the dechlorination rates declined with increasing arsenic concentrations in both As(III/V) scenarios, the inhibitory impact was more pronounced in As(III)-amended groups compared to As(V)-amended groups. Moreover, the vinyl chloride (VC)-to-ethene step was more susceptible to arsenic exposure compared to the trichloroethene (TCE)-to-dichloroethane (DCE) step, while high levels of arsenic exposure [e.g. As(III) > 75 μM] can induce significant accumulation of VC. Functional gene variations and microbial community analyses revealed that As(III/V) affected reductive dechlorination by directly inhibiting organohalide-respiring bacteria (OHRB) and indirectly inhibiting synergistic populations such as acetogens. Metagenomic results indicated that arsenic metabolic and efflux mechanisms were identical among different Dhc strains, and variations in arsenic uptake pathways were possibly responsible for their differential responses to arsenic exposures. By comparison, fermentative bacteria showed high potential for arsenic resistance due to their inherent advantages in arsenic detoxification and efflux mechanisms. Collectively, our findings expanded the understanding of the response patterns of different functional populations to arsenic stress in the dechlorinating consortium and provided insights into modifying bioremediation strategies at co-contaminated sites for furtherance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bioelectrochemical system is considered as a promising approach for enhanced bio-dechlorination. However, the mechanism of extracellular electron transfer in the dechlorinating consortium is still a controversial issue. In this study, bioelectrochemical systems were established with cathode potential settings at -0.30 V (vs. SHE) for trichloroethylene reduction. The average dechlorination rate (102.0 μM Cl·d -1 ) of biocathode was 1.36 times higher than that of open circuit (74.7 μM Cl·d -1 ). Electrochemical characterization via cyclic voltammetry illustrated that electrostimulation promoted electrochemical activity for redox reactions. Moreover, bacterial community structure analyses indicated electrical stimulation facilitated the enrichment of electroactive and dechlorinating populations on cathode. Metagenomic and quantitative polymerase chain reaction (qPCR) analyses revealed that direct electron transfer (via electrically conductive pili, multi-heme c-type cytochromes) between Axonexus and Desulfovibrio/cathode and indirect electron transfer (via riboflavin) for Dehalococcoides enhanced dechlorination process in BES. Overall, this study verifies the effectiveness of electrostimulated bio-dechlorination and provides novel insights into the mechanisms of dechlorination process enhancement in bioelectrochemical systems through electron transfer networks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Peritoneal dialysis (PD) catheter-related infection (i.e. exit-site infection and tunnel infection) is one of the main causes of PD-related peritonitis. If it cannot be controlled effectively, it could lead to PD technique failure. Therefore, timely and effective diagnosis and treatment and active prevention so as to reduce PD catheter-related infection is an important treatment goal in PD patients. PD catheter exit-site infection (ESI) and tunnel infection can be caused by a variety of microorganisms, mainly bacteria, while fungi are very rare. Few public data can be used to guide treatment of PD catheter-related fungal infection, and there is no related report in China till now. Once fungal peritonitis occurred, the patient can only withdraw from PD treatment. Here, we report a case of fungal PD catheter ESI combined with tunnel infection which was successfully diagnosed and treated in our PD center. A 71-year-old woman came to clinic because of "PD for 5 years, secretions from exit site for 8 days and aggravation for 1 day". The patient suffered from peritonitis, ESI and tunnel infection for many times in the past 5 years, involving a variety of pathogens. Eight days before, she found white viscous discharge from exit site. The subcutaneous cuff completely came out of it and rubbed its skin. The Schaefer exit-site score was 3 points. Due to the suspected ESI 2 months before, the discharge swab for bacterial culture was positive for Pseudomonas aeruginosa , so the exit site swab for bacterial culture was done again, and gentamicin injection was applied topically once a day for empirical treatment. The exit site was evaluated one day before: The subcutaneous tunnel was significantly swollen and slightly tender at 2.5 cm away from the exit site, and with white medium amount of viscous secretions. The exit-site score increased to 4 points. Routine test of dialysis effluent was (-). The bacterial culture of the exit-site discharge was rechecked twice, and Candida parapsilosis was positive for two times, so the diagnosis of fungal PD catheter ESI combined with tunnel infection was clear. Immediately we searched for the causes of ESI and tunnel infection. We found that the patient had a suspicious history of gray toenail on the foot. The toenail smear was positive for fungi and visible hyphae. She washed feet with hands every day, and washed clothes on a low bench every day, which made the exit-site and tunnel squeezed for a long time. Based on the above causes, we gave her comprehensive treatment as follows: For ESI and tunnel fungal infections, fluco-nazole was used systemically according to the drug sensitivity results, and miconazole cream was applied to the exit-site locally. For the subcutaneous cuff that came out completely, daily iodophor disinfection was given locally. At the same time, local antifungal treatment was given to the foot. We followed up closely during treatment, evaluated the exit-site every 2-3 days, and took photos of the exit-site to dynamically observe the effect. After 14 days of treatment, the exit-site score continued to be 0-1, the bacterial culture of the exit-site was negative, the cuff culture was negative, and the tunnel B-ultrasound was normal. The patient had been followed up regularly once a month for 60 months, no ESI and tunnel infection occurred. Fungal PD catheter ESI and tunnel infection are rare complications of PD. When the standard anti-infection treatment is ineffective, the possibility of fungal infection should be considered, so as to avoid prolonged use of antibiotics, aggravating fungal infection, and even progressing to fungal peritonitis, leading to withdrawal from PD. Accurate exit-site evaluation is helpful for timely diagnosis and early treatment of ESI and tunnel infection. The exit-site discharge culture and drug sensitivity test before treatment are helpful to identify the pathogen and adjust subsequent treatment. At the same time, repeated discharge culture is required in order to exclude positive fungal culture results caused by contamination. Once fungal catheter-related infection is diagnosed, we should search for possible causes actively, subsequent targeted and comprehensive treatment plays a decisive role for the prognosis of patients.

Objective: To observe the differences in biochemical indexes and AIDS-related complications at baseline in HIV-infected patients with different levels of immune reconstitution to antiretroviral therapy (ART). Methods: The subjects were treat-naïve adult HIV-infected patients who were followed up for more than 24 months in the Guangzhou Eighth People's Hospital affiliated infection clinic at Guangzhou Medical University from January 2010 to December 2017. CD4 + T lymphocyte count at baseline at <200, 200-350, and >350 cells/µl levels were divided into poor, partial, and good immune reconstitution groups. The Kruskal-Wallis H and chi-square tests were used to analyze the differences in baseline sociodemographic characteristics, biochemical indexes, and AIDS-related complications among different groups. The SPSS 20.0 software was used for statistical analysis. Results: Among the 3 900 HIV-infected individuals, 385 cases (9.9%), 1 206 cases (30.9%), and 2 309 cases (59.2%) were grouped into poor, partial and good immune reconstitution groups, respectively. The baseline biochemical indexes of leukocyte, platelet, hemoglobin, TG, TC, FPG, AST, ALT and total bilirubin in the poor immune reconstitution group were significantly different from those in the good immune reconstitution group (all P <0.05). The proportion of AIDS-related complications at baseline in the poor immune reconstitution group, such as tuberculosis, pneumocystis yeli pneumonia, disseminated mycosis, esophageal candidiasis, extrapulmonary tuberculosis, dermatitis, oral candidiasis, oral mucous leukoplakia, continuous diarrhea for more than 1 month and continuous or intermittent fever for more than 1 month, was significantly higher than that in the good immune reconstitution group (all P <0.05). Conclusions: The biochemical indexes and AIDS-related complications in HIV-infected patients with different levels of immune reconstitution were significantly different at baseline. Attention should be paid to monitoring abnormal biomedical indicators and AIDS-related complications at baseline.

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 (S 0 ) 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.

DNA barcoding has greatly facilitated studies of taxonomy, biodiversity, biological conservation, and ecology. Here, we establish a reliable DNA barcoding library for Chinese snakes, unveiling hidden diversity with implications for taxonomy, and provide a standardized tool for conservation management. Our comprehensive study includes 1638 cytochrome c oxidase subunit I (COI) sequences from Chinese snakes that correspond to 17 families, 65 genera, 228 named species (80.6% of named species) and 36 candidate species. A barcode gap analysis reveals gaps, where all nearest neighbour distances exceed maximum intraspecific distances, in 217 named species and all candidate species. Three species-delimitation methods (ABGD, sGMYC, and sPTP) recover 320 operational taxonomic units (OTUs), of which 192 OTUs correspond to named and candidate species. Twenty-eight other named species share OTUs, such as Azemiops feae and A. kharini, Gloydius halys, G. shedaoensis, and G. intermedius, and Bungarus multicinctus and B. candidus, representing inconsistencies most probably caused by imperfect taxonomy, recent and rapid speciation, weak taxonomic signal, introgressive hybridization, and/or inadequate phylogenetic signal. In contrast, 43 species and candidate species assign to two or more OTUs due to having large intraspecific distances. If most OTUs detected in this study reflect valid species, including the 36 candidate species, then 30% more species would exist than are currently recognized. Several OTU divergences associate with known biogeographic barriers, such as the Taiwan Strait. In addition to facilitating future studies, this reliable and relatively comprehensive reference database will play an important role in the future monitoring, conservation, and management of Chinese snakes., (© 2023 John Wiley & Sons Ltd.)

Purpose: The present study aimed to investigate the clinical prognostic significance of radiomics signature (R-signature) in patients with gastric neuroendocrine neoplasm (GNEN)., Methods and Materials: A retrospective study of 182 patients with GNEN who underwent dual-phase enhanced computed tomography (CT) scanning was conducted. LASSO-Cox regression analysis was used to screen the features and establish the arterial, venous and the arteriovenous phase combined R-signature, respectively. The association between the optimal R-signature with the best prognostic performance and overall survival (OS) was assessed in the training cohort and verified in the validation cohort. Univariate and multivariate Cox regression analysis were used to identify the significant factors of clinicopathological characteristics for OS. Furthermore, the performance of a combined radiomics-clinical nomogram integrating the R-signature and independent clinicopathological risk factors was evaluated., Results: The arteriovenous phase combined R-signature had the best performance in predicting OS, and its C-index value was better than the independent arterial and venous phase R-signature (0.803 vs 0.784 and 0.803 vs 0.756, P<0.001, respectively). The optimal R-signature was significantly associated with OS in the training cohort and validation cohort. GNEN patients could be successfully divided into high and low prognostic risk groups with radiomics score median. The combined radiomics-clinical nomogram combining this R-signature and independent clinicopathological risk factors (sex, age, treatment methods, T stage, N stage, M stage, tumor boundary, Ki67, CD56) exhibited significant prognostic superiority over clinical nomogram, R-signature alone, and traditional TNM staging system (C-index, 0.882 vs 0.861, 882 vs 0.803, and 0.882 vs 0.870 respectively, P<0.001). All calibration curves showed remarkable consistency between predicted and actual survival, and decision curve analysis verified the usefulness of the combined radiomics-clinical nomogram for clinical practice., Conclusions: The R-signature could be used to stratify patients with GNEN into high and low risk groups. Furthermore, the combined radiomics-clinical nomogram provided better predictive accuracy than other predictive models and might aid clinicians with therapeutic decision-making and patient counseling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Han, Cheng, Wang, Li, Zhao and Gao.)

In our previous study, we identified a metabolite of Bacillus subtilis BS-Z15 (a strain with probiotic characteristics) that could improve immunity in mice. In the present study, we examined the effects of B. subtilis BS-Z15 and its metabolites on body weight gain and the intestinal microbiota of mice. Sixty 25-day-old male Kunming white mice were selected and randomly divided into four groups: control group (A), daily saline gavage; B. subtilis-treated group (B), single gavage (1 × 10 9  CFU/time/animal/day); group D, 14 consecutive gavages (1 × 10 9  CFU/time/animal/day); and B. subtilis metabolite-treated group (E), 30 consecutive gavages (90 mg kg -1 /time/animal/day). High-throughput sequencing technology was used to analyze intergroup differences in the mouse intestinal microbiota. The results showed that the three treated groups had significantly slower body weight gain compared with the control group, which lasted until the 45 days (P < 0.05), and the daily food intake of the treated mice was higher (P < 0.05). The intestinal microbiota structure of the mice in the treated groups was significantly altered compared with that in the control group, suggesting that B. subtilis BS-Z15 may regulate the weight gain of animals by affecting their intestinal bacterial composition. After stopping the gavage of B. subtilis BS-Z15, the abundance of this strain in the small intestine of the mice gradually decreased and its presence was undetectable at 45 days, indicating that B. subtilis BS-Z15 could not colonize the intestine of these mice. These findings suggest that B. subtilis BS-Z15 may regulate intestinal microbiota through its metabolites to reduce weight gain., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study quantitatively investigated the effect of dissolved oxygen (DO) concentration on aerobic denitrification, and showed the mechanism of aerobic denitrification from the perspective of electron competition by cultivating Pseudomonas stutzeri T13, a typical aerobic denitrifier, in an oxygen-based membrane biofilm reactor (O 2 -based MBfR). The experiments showed that when the O 2 pressure increased from 2 to 10 psig , the average effluent DO concentration during steady-state phases increased from 0.02 to 4.23 mg/L, and the corresponding mean NO 3 - -N removal efficiency slightly decreased from 97.2 % to 90.9 %. Compared to the maximum theoretical flux of O 2 in various phases, the actual O 2 transfer flux increased from a limited status (2.07 e - eq m -2 d -1 at 2 psig) to an excessive status (5.58 e - eq m -2 d -1 at 10 psig). The increase of DO inhibited the electron availability for aerobic denitrification, which decreased from 23.97 % to 11.46 %, accompanying the increased electron availability for aerobic respiration from 15.87 % to 28.36 %. Unlike the napA and norB genes, the expression of the nirS and nosZ genes was significantly affected by DO, with the highest relative fold-changes of 6.5 and 6.13 at 4 psig O 2 , respectively. The results contribute to clarifying the mechanism of aerobic denitrification from the quantitative perspective of electron distribution and the qualitative perspective of gene expression, which benefits the control and practical application of aerobic denitrification for wastewater treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis., Results: The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5)., Conclusions: BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity., (© 2023. The Author(s).)

Gastric cancer (GC) is defined as the primary epithelial malignancy derived from the stomach, and it is a complicated and heterogeneous disease with multiple risk factors. Despite its overall declining trend of incidence and mortality in various countries over the past few decades, GC remains the fifth most common malignancy and the fourth leading cause of cancer-related death globally. Although the global burden of GC has shown a significant downward trend, it remains severe in certain areas, such as Asia. GC ranks third in incidence and mortality among all cancer types in China, and it accounts for nearly 44.0% and 48.6% of new GC cases and GC-related deaths in the world, respectively. The regional differences in GC incidence and mortality are obvious, and annual new cases and deaths are increasing rapidly in some developing regions. Therefore, early preventive and screening strategies for GC are urgently needed. The clinical efficacies of conventional treatments for GC are limited, and the developing understanding of GC pathogenesis has increased the demand for new therapeutic regimens, including immune checkpoint inhibitors, cell immunotherapy and cancer vaccines. The present review describes the epidemiology of GC worldwide, especially in China, summarizes its risk and prognostic factors, and focuses on novel immunotherapies to develop therapeutic strategies for the management of GC patients., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Electrokinetic-enhanced bioremediation (EK-Bio), particularly bioaugmentation with injection of biodehalogenation functional microbes such as Dehalococcoides , has been documented to be effective in treating a low-permeability subsurface matrix contaminated with chlorinated ethenes. However, the spatio-temporal variations of indigenous microbial community and biodehalogenation activity of the background matrix, a fundamental aspect for understanding EK-Bio, remain unclear. To fill this gap, we investigated the variation of trichloroethylene (TCE) biodehalogenation activity in response to indigenous microbial community succession in EK-Bio by both column and batch experiments. For a 195 day EK-Bio column (∼1 V/cm, electrolyte circulation, lactate addition), biodehalogenation activity occurred first near the cathode (<60 days) and then spread to the anode (>90 days), which was controlled by electron acceptor (i.e., Fe(III)) competition and microbe succession. Amplicon sequencing and metagenome analysis revealed that iron-reducing bacteria ( Geobacter , Anaeromyxobacter , Geothrix ) were enriched within initial 60 d and were gradually replaced by organohalide-respiring bacteria (versatile Geobacter and obligate Dehalobacter ) afterward. Iron-reducing bacteria required an initial long time to consume the competitive electron acceptors so that an appropriate reductive condition could be developed for the enrichment of organohalide-respiring bacteria and the enhancement of TCE biodehalogenation activity.

Doxorubicin (DOX), which is widely used for the treatment of cancer, induces cardiomyopathy associated with NADPH oxidase-derived reactive oxygen species. GSK2795039 is a novel small molecular NADPH oxidase 2 (Nox2) inhibitor. In this study, we investigated whether GSK2795039 prevents receptor-interacting protein kinase 1 (RIP1)-RIP3-mixed lineage kinase domain-like protein (MLKL)-mediated cardiomyocyte necroptosis in DOX-induced heart failure through NADPH oxidase inhibition. Eight-week old mice were randomly divided into 4 groups: control, GSK2795039, DOX and DOX plus GSK2795039. H9C2 cardiomyocytes were treated with DOX and GSK2795039. In DOX-treated mice, the survival rate was reduced, left ventricular (LV) end-systolic dimension was increased and LV fractional shortening was decreased, and these alterations were attenuated by the GSK2795039 treatment. GSK2795039 inhibited not only myocardial NADPH oxidase subunit gp91phox (Nox2) protein, but also p22phox, p47phox and p67phox proteins and prevented oxidative stress 8-hydroxy-2'-deoxyguanosine levels in DOX-treated mice. RIP3 protein and phosphorylated RIP1 (p-RIP1), p-RIP3 and p-MLKL proteins, reflective of their respective kinase activities, markers of necroptosis, were markedly increased in DOX-treated mice, and the increases were prevented by GSK2795039. GSK2795039 prevented the increases in serum lactate dehydrogenase and myocardial fibrosis in DOX-treated mice. Similarly, in DOX-treated cardiomyocytes, GSK2795039 improved cell viability, attenuated apoptosis and necrosis and prevented the increases in p-RIP1, p-RIP3 and p-MLKL expression. In conclusion, GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis through inhibition of NADPH oxidase-derived oxidative stress, leading to the improvement of myocardial remodeling and function in DOX-induced heart failure. These findings suggest that GSK2795039 may have implications for the treatment of DOX-induced cardiomyopathy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Two prenylated 2-arylbenzofurans were isolated from roots of Artocarpus heterophyllus, with a combination of various chromatographic approaches, including ODS, MCI, Sephadex LH-20, and semipreparative high performance liquid chromatography(HPLC). They were identified as 5-[6-hydroxy-4-methoxy-5,7-bis(3-methylbut-2-enyl)benzofuran-2-yl]-1,3-benzenediol(1) and 5-[2H,9H-2,2,9,9-tetramethyl-furo[2,3-f]pyrano[2,3-h][1]benzopyran-6-yl]-1,3-benzenediol(2) with spectroscopic methods, such as HR-ESI-MS, IR, 1D NMR, and 2D NMR, and named artoheterins B(1) and C(2), respectively. The anti-respiratory burst activities of the two compounds were evaluated with rat polymorphonuclear neutrophils(PMNs) stimulated by phorbol 12-myristate 13-acetate(PMA). The results showed that 1 and 2 exhibited significant inhibitory effect on respiratory burst of PMNs with IC&#95;(50) values of 0.27 and 1.53 μmol·L~(-1), respectively.

Producing stable nitrite is a necessity for anaerobic ammonium oxidation (anammox) but remains a huge challenge. Here, we describe the design and operation of a hydrogenotrophic denitratation system that stably reduced >90% nitrate to nitrite under self-alkaline conditions of pH up to 10.80. Manually lowering the pH to a range of 9.00-10.00 dramatically decreased the nitrate-to-nitrite transformation ratio to <20%, showing a significant role of high pH in denitratation. Metagenomics combined with metatranscriptomics indicated that six microorganisms, including a Thauera member, dominated the community and encoded the various genes responsible for hydrogen oxidation and the complete denitrification process. During denitratation at high pH, transcription of periplasmic genes napA , nirS , and nirK , whose products perform nitrate and nitrite reduction, decreased sharply compared to that under neutral conditions, while narG , encoding a membrane-associated nitrate reductase, remained transcriptionally active, as were genes involved in intracellular proton homeostasis. Together with no reduction in only nitrite-amended samples, these results disproved the electron competition between reductions of nitrate and nitrite but highlighted a lack of protons outside cells constraining biological nitrite reduction. Overall, our study presents a stably efficient strategy for nitrite production and provides a major advance in the understanding of denitratation.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) has been recognized as a sustainable process for simultaneous removal of nitrogen and methane. The metabolisms of denitrifying anaerobic methanotrophs, including Candidatus Methanoperedens and Candidatus Methylomirabilis, have been well studied. However, potential roles of heterotrophs co-existing with these anaerobic methanotrophs are generally overlooked. In this study, we pulse-fed methane and nitrate into an anaerobic laboratory sequencing batch bioreactor and enriched a mixed culture with stable nitrate removal rate (NRR) of ∼28 mg NO 3 - -N L -1 d -1 . Microbial community analysis indicates abundant heterotrophs, e.g., Arenimonas (5.3%-18.9%) and Fimbriimonadales ATM1 (6.4%), were enriched together with denitrifying anaerobic methanotrophs Ca. Methanoperedens (10.8%-13.2%) and Ca. Methylomirabilis (27.4%-34.3%). The results of metagenomics and batch tests suggested that the denitrifying anaerobic methanotrophs were capable of generating methane-derived intermediates (i.e., formate and acetate), which were employed by non-methanotrophic heterotrophs for denitrification and biomass growth. These findings offer new insights into the roles of heterotrophs in n-DAMO mixed culture, which may help to optimize n-DAMO process for nitrogen removal from wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this work, a simple one-step hydrothermal method was employed to prepare the Ce-doped Fe 2 O 3 ordered nanorod arrays (CFT). The Ce doping successfully narrowed the band gap of Fe 2 O 3 , which improved the visible light absorption performance. In addition, with the help of Ce doping, the recombination of electron/hole pairs was significantly inhibited. The external voltage will make the performance of the Ce-doped sample better. Therefore, the Ce-doped Fe 2 O 3 has reached superior photoelectrochemical (PEC) performance with a high photocurrent density of 1.47 mA/cm 2 at 1.6 V vs. RHE (Reversible Hydrogen Electrode), which is 7.3 times higher than that of pristine Fe 2 O 3 nanorod arrays (FT). The Hydrogen (H 2 ) production from PEC water splitting of Fe 2 O 3 was highly improved by Ce doping to achieve an evolution rate of 21 μmol/cm 2 /h.

Dissemination of antibiotic resistance genes (ARGs) through natural transformation is facilitated by factors that stabilize extracellular DNA (eDNA) and that induce reactive oxygen species (ROS) that permeabilize receptor cells and upregulate transformation competence genes. In this study, we demonstrate that Deinococcus radiodurans can mitigate this ARG dissemination pathway by removing both eDNA and ROS that make recipient cells more vulnerable to transformation. We used plasmid RP4 as source of extracellular ARGs ( tetA , aphA , and blaTEM-2 ) and the opportunistic pathogen Enterococcus faecalis as receptor. The presence of D. radiodurans significantly reduced the transformation frequency from 2.5 ± 0.7 × 10 -6 to 7.4 ± 1.4 × 10 -7 ( p < 0.05). Based on quantification of intracellular ROS accumulation and superoxide dismutase (SOD) activity, and quantitative polymerase chain reaction (qPCR) and transcriptomic analyses, we propose two mechanisms by which D. radiodurans mitigates E. faecalis transformation by ARGs: (a) residual antibiotics induce D. radiodurans to synthesize liposoluble carotenoids that scavenge ROS and thus mitigate the susceptibility of E. faecalis for eDNA uptake, and (b) eDNA induces D. radiodurans to synthesize extracellular nucleases that degrade eARGs. This mechanistic insight informs biological strategies (including bioaugmentation) to curtail the spread of ARGs through transformation.

Purpose: Preoperative evaluation of lymph node metastasis (LNM) is the basis of personalized treatment of locally advanced gastric cancer (LAGC). We aim to develop and evaluate CT-based model using deep learning features to preoperatively predict LNM in LAGC., Methods: A combined size of 523 patients who had pathologically confirmed LAGC were retrospectively collected between August 2012 and July 2019 from our hospital. Five pre-trained convolutional neural networks were exploited to extract deep learning features from pretreatment CT images. And the support vector machine (SVM) was employed as the classifier. We assessed the performance using the area under the receiver operating characteristics curve (AUC) and selected an optimal model, which was compared with a radiomics model developed from the training cohort. A clinical model was built with clinical factors only for baseline comparison., Results: The optimal model with features extracted from ResNet yielded better performance with AUC of 0.796 [95% confidence interval (95% CI), 0.715-0.865] and accuracy of 75.2% (95% CI, 67.2%-81.5%) in the testing cohort, compared with 0.704 (0.625-0.783) and 61.8% (54.5%-69.9%) for the radiomics model. The predictive performance of all the radiological models were significantly better than the clinical model., Conclusion: The novel and noninvasive deep learning approach could provide efficient and accurate prediction of lymph node metastasis in LAGC, and benefit clinical decision making of therapeutic strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhao, Li, Liang, Gao and Cheng.)

Persistent microbial symbioses can confer greater fitness to their host under unfavorable conditions, but manipulating such beneficial interactions necessitates a mechanistic understanding of the consistently important microbiomes for the plant. Here, we examined the phylogenetic profiles and plant-beneficial traits of the core microbiota that consistently inhabits the rhizosphere of four divergent Cd hyperaccumulators and an accumulator. We evidenced the existence of a conserved core rhizosphere microbiota in each plant distinct from that in the non-hyperaccumulating plant. Members of Burkholderiaceae and Sphingomonas were the shared cores across hyperaccumulators and accumulators. Several keystone taxa in the rhizosphere networks were part of the core microbiota, the abundance of which was an important predictor of plant Cd accumulation. Furthermore, an inoculation experiment with synthetic communities comprising isolates belonging to the shared cores indicated that core microorganisms could facilitate plant growth and metal tolerance. Using RNA-based stable isotope probing, we discovered that abundant core taxa overlapped with active rhizobacteria utilizing root exudates, implying that the core rhizosphere microbiota assimilating plant-derived carbon may provide benefits to plant growth and host phenotype such as Cd accumulation. Our study suggests common principles underpinning hyperaccumulator-microbiome interactions, where plants consistently interact with a core set of microbes contributing to host fitness and plant performance. These findings lay the foundation for harnessing the persistent root microbiomes to accelerate the restoration of metal-disturbed soils.

Aims: To investigate the effect of erythropoietin (EPO) on the differentiation of neural stem cells (NSCs)/neural progenitors (NPs) in the treatment of hypoxic-ischemic injury and its potential mechanisms., Methods: Fetal NSCs/NPs were treated with EPO after oxygen and glucose deprivation/reoxygenation (OGD/R). Cell viability, proliferation, and differentiation of NSCs/NPs were detected by CellTiter-Glo, Edu assay, flow cytometry, and quantitative real-time PCR (qPCR). Immunofluorescence staining, co-immunoprecipitation (Co-IP), and western blotting were used to test the existence of EPO receptor/β common receptor (EPOR/βCR) heterodimer on NSCs/NPs and the possible pathway., Results: EPO treatment at different time points increased cell viability without affecting proliferation. EPO treatment immediately after OGD/R promoted oligodendrocyte and astrocyte differentiation, while decreasing neuronal differentiation of NSCs/NPs. EPOR/βCR heterodimer existed on the cell surface of the fetal cortical NSCs/NPs, EPO treatment significantly increased the mRNA expression of βCR and elevated the correlation between EPOR and βCR levels. In addition, mass spectrometry analysis identified Syne-1 as a downstream signaling molecule of the EPOR/βCR heterodimer. Immunofluorescence staining and western blotting indicated that the βCR/Syne-1/H3K9me3 pathway was possibly involved in the differentiation of fetal neural stem cells into the glial cell effect of EPO., Conclusion: EPO treatment immediately after OGD/R could not facilitate fetal NSCs/NPs neurogenesis but promoted the formation of the EPOR/βCR heterodimer on fetal NSCs/NPs, which mediates its function in glial differentiation., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The aphid parasitoid Aphelinus asychis Walker is an important biological control agent against many aphid species. In this study, we examined whether the rearing host aphid species (the pea aphid, Acyrthosiphon pisum and the grain aphid, Sitobion avenae ) affect the performance of A. asychis . We found that A. pisum -reared A. asychis showed a significantly larger body size (body length and hind tibia length) and shorter developmental time than S. avenae -reared A. asychis . There was no difference in the sex ratio between them. The longevity of A. pisum -reared A. asychis was also significantly longer than that of S. aveane -reared A. asychis . Furthermore, A. pisum -reared A. asychis presented stronger parasitic capacity and starvation resistance than S. aveane -reared A. asychi . In addition, host aphid alteration experiments showed that A. asychis only takes two generations to adapt to its new host. Taken together, these results revealed that A. pisum is a better alternative host aphid for mass-rearing and releasing of A. asychis . The body size plasticity of A. asychis is also discussed.

Microbial oxidation of organic compounds can promote arsenic release by reducing soil-associated arsenate to the more mobile form arsenite. While anaerobic oxidation of methane has been demonstrated to reduce arsenate, it remains elusive whether and to what extent aerobic methane oxidation (aeMO) can contribute to reductive arsenic mobilization. To fill this knowledge gap, we performed incubations of both microbial laboratory cultures and soil samples from arsenic-contaminated agricultural fields in China. Incubations with laboratory cultures showed that aeMO could couple to arsenate reduction, wherein the former bioprocess was carried out by aerobic methanotrophs and the latter by a non-methanotrophic bacterium belonging to a novel and uncultivated representative of Burkholderiaceae . Metagenomic analyses combined with metabolite measurements suggested that formate served as the interspecies electron carrier linking aeMO to arsenate reduction. Such coupled bioprocesses also take place in the real world, supported by a similar stoichiometry and gene activity in the incubations with natural paddy soils, and contribute up to 76.2% of soil-arsenic mobilization into pore waters in the top layer of the soils where oxygen was present. Overall, this study reveals a previously overlooked yet significant contribution of aeMO to reductive arsenic mobilization.

Background: The gut microbiota (GM) has been proven to play a role in the regulation of host lipid metabolism, which provides a new theory about the pathogenesis of dyslipidemia. However, the associations of GM with dyslipidemia based on sex differences remain unclear and warrant elucidation., Aim: To investigate the associations of GM features with serum lipid profiles based on sex differences in a Chinese population., Methods: This study ultimately recruited 142 participants (73 females and 69 males) at Honghui Hospital, Xi'an Jiaotong University. The anthropometric and blood metabolic parameters of all participants were measured. According to their serum lipid levels, female and male participants were classified into a high triglyceride (H&#95;TG) group, a high total cholesterol (H&#95;CHO) group, a low high-density lipoprotein cholesterol (L&#95;HDL-C) group, and a control (CON) group with normal serum lipid levels. Fresh fecal samples were collected for 16S rRNA gene sequencing. UPARSE software, QIIME software, the RDP classifier and the FAPROTAX database were used for sequencing analyses., Results: The GM composition at the phylum level included Firmicutes and Bacteroidetes as the core GM. Different GM features were identified between females and males, and the associations between GM and serum lipid profiles were different in females and males. The GM features in different dyslipidemia subgroups changed in both female patients and male patients. Proteobacteria, Lactobacillaceae, Lactobacillus and Lactobacillus&#95;salivarius were enriched in H&#95;CHO females compared with CON females, while Coriobacteriia were enriched in L&#95;HDL-C females. In the comparison among the three dyslipidemia subgroups in females, Lactobacillus&#95;salivarius were enriched in H&#95;CHO females, and Prevotellaceae were enriched in L&#95;HDL-C females. Compared with CON or H&#95;TG males, Prevotellaceae, unidentified&#95;Ruminococcaceae , Roseburia and Roseburia&#95;inulinivorans were decreased in L&#95;HDL-C males ( P value < 0.05), and linear discriminant analysis effect size analysis indicated an enrichment of the above GM taxa in H&#95;TG males compared with other male subgroups. Additionally, Roseburia&#95;inulinivorans abundance was positively correlated with serum TG and total cholesterol levels, and Roseburia were positively correlated with serum TG level. Furthermore, Proteobacteria (0.724, 95%CI: 0.567-0.849), Lactobacillaceae (0.703, 95%CI: 0.544-0.832), Lactobacillus (0.705, 95%CI: 0.547-0.834) and Lactobacillus&#95;salivarius (0.706, 95%CI: 0.548-0.835) could distinguish H&#95;CHO females from CON females, while Coriobacteriia (0.710, 95%CI: 0.547-0.841), Coriobacteriales (0.710, 95%CI: 0.547-0.841), Prevotellaceae (0.697, 95%CI: 0.534-0.830), Roseburia (0.697, 95%CI: 0.534-0.830) and Roseburia&#95;inulinivorans (0.684, 95%CI: 0.520-0.820) could discriminate H&#95;TG males from CON males. Based on the predictions of GM metabolic capabilities with the FAPROTAX database, a total of 51 functional assignments were obtained in females, while 38 were obtained in males. This functional prediction suggested that cellulolysis increased in L&#95;HDL-C females compared with CON females, but decreased in L&#95;HDL-C males compared with CON males., Conclusion: This study indicates associations of GM with serum lipid profiles, supporting the notion that GM dysbiosis may participate in the pathogenesis of dyslipidemia, and sex differences should be considered., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The growth and development of biological tissues and organs strongly depend on the requirements of their multiple functions. Plant veins yield efficient nutrient transport and withstand various external loads. Victoria cruziana , a tropical species of the Nymphaeaceae family of water lilies, has evolved a network of three-dimensional and rugged veins, which yields a superior load-bearing capacity. However, it remains elusive how biological and mechanical factors affect their unique vein layout. In this paper, we propose a multi-functional and large-scale topology optimization method to investigate the morphomechanics of Victoria cruziana veins, which optimizes both the structural stiffness and nutrient transport efficiency. Our results suggest that increasing the branching order of radial veins improves the efficiency of nutrient delivery, and the gradient variation of circumferential vein sizes significantly contributes to the stiffness of the leaf. In the present method, we also consider the optimization of the wall thickness and the maximum layout distance of circumferential veins. Furthermore, biomimetic leaves are fabricated by using the three-dimensional printing technique to verify our theoretical findings. This work not only gains insights into the morphomechanics of Victoria cruziana veins, but also helps the design of, for example, rib-reinforced shells, slabs and dome skeletons.

Effective conservation of threatened biota relies on accurate assessments and scientific guidance. As an unfortunate example, Chinese giant salamanders ( Andrias , CGS) remain critically endangered in nature. Misguided conservation efforts, e.g., commercial propagation and releasing of millions of likely non-indigenous or interspecific hybrids, have further compromised conservation initiatives. Limited information on wild populations of CGS poses a significant conservation challenge. Following 18-month long field monitoring, we now report the discovery of a wild population of CGS in a closed nature reserve in Jiangxi Province, China. Genomic assessments reveal its genetic distinctiveness and do not detect genetic admixture with other species. Based on morphological and molecular evidences, we describe this CGS as a new species Andrias jiangxiensis sp. nov. This is the only known species of CGS today with a genetically pure, reproducing, in situ population. This discovery emphasizes the important role that closed nature reserves play in protecting species, and the necessity of integrating long-term field monitoring and genetic assessments. It sets a new pathway for discovering and conserving endangered species, especially for those biotas that are similarly being extirpated by anthropogenic translocations and overexploitation.

Activated sludge of wastewater treatment plants harbors a very high diversity of both microorganisms and viruses, wherein the latter control microbial dynamics and metabolisms by infection and lysis of cells. However, it remains poorly understood how viruses impact the biochemical processes of activated sludge, for example in terms of treatment efficiency and pollutant removal. Using metagenomic and metatranscriptomic deep sequencing, the present study recovered thousands of viral sequences from activated sludge samples of three conventional wastewater treatment plants. Gene-sharing network indicated that most of viruses could not be assigned to known viral genera, implying activated sludge as an underexplored reservoir for new viruses and viral diversity. In silico predictions of virus-host linkages demonstrated that infected microbial hosts, mostly belonging to bacteria, were transcriptionally active and able to hydrolyze polymers including starches, celluloses, and proteins. Some viruses encode auxiliary metabolic genes (AMGs) involved in carbon, nitrogen, and sulfur cycling, and antibiotic resistance genes (ARGs) for resistance to multiple drugs. The virus-encoded AMGs may enhance the biodegradation of contaminants like starches and celluloses, suggesting a positive role for viruses in strengthening the performance of activated sludge. However, ARGs would be disseminated to different microorganisms using viruses as gene shuttles, demonstrating the possibility for viruses to facilitate the spread of antibiotic resistance in the environment. Collectively, this study highlights the mixed blessing of viruses in wastewater treatment plants, and deciphers how they manipulate the biochemical processes in the activated sludge, with implications for both environmental protection and ecosystem security., (Copyright © 2022. Published by Elsevier Ltd.)