Enhanced growth of wheat in contaminated fields via synthetic microbiome as revealed by genome-scale metabolic modeling.

The relationship between plants and soil microbial communities is complex and subtle, with microbes playing a crucial role in plant growth. Autochthonous bioaugmentation and nutrient biostimulation are promising bioremediation methods for herbicides in contaminated agricultural soils, but how microbes interact to promote biodegradation and plant growth on barren fields, especially in response to the treatment of the herbicide bromoxynil after wheat seedlings, remains poorly understood. In this study, we explored the microbial community reassembly process from the three-leaf stage to the tillering stage of wheat and put forward the idea of using the overlapping results of three methods (network Zi-Pi analysis, LEfSe analysis, and Random Forest analysis) as keystones for the simplification and optimization of key microbial species in the soil. Then we used genome-scale metabolic models (GSMMs) to design a targeted synthetic microbiome for promoting wheat seedling growing. The results showed that carbon source was more helpful in enriching soil microbial diversity and promoting the role of functional microbial communities, which facilitated the degradation of bromoxynil. Designed a multifunctional synthetic consortium consisting of seven non-degraders which unexpectedly assisted in the degradation of indigenous bacteria, which increased the degradation rate of bromoxynil by 2.05 times, and when adding nutritional supplementation, it increased the degradation rate by 3.65 times. In summary, this study provides important insights for rational fertilization and precise microbial consortium management to improve plant seedling growth in contaminated fields.

Bacterial growth and environmental adaptation via thiamine biosynthesis and thiamine-mediated metabolic interactions.

Understanding the ancestral transition from anaerobic to aerobic lifestyles is essential for comprehending life's early evolution. However, the biological adaptations occurring during this crucial transition remain largely unexplored. Thiamine is an important cofactor involved in central carbon metabolism and aerobic respiration. Here, we explored the phylogenetic and global distribution of thiamine-auxotrophic and thiamine-prototrophic bacteria based on the thiamine biosynthetic pathway in 154 838 bacterial genomes. We observed strong coincidences of the origin of thiamine-synthetic bacteria with the "Great Oxygenation Event," indicating that thiamine biosynthesis in bacteria emerged as an adaptation to aerobic respiration. Furthermore, we demonstrated that thiamine-mediated metabolic interactions are fundamental factors influencing the assembly and diversity of bacterial communities by a global survey across 4245 soil samples. Through our newly established stable isotope probing-metabolic modeling method, we uncovered the active utilization of thiamine-mediated metabolic interactions by bacterial communities in response to changing environments, thus revealing an environmental adaptation strategy employed by bacteria at the community level. Our study demonstrates the widespread thiamine-mediated metabolic interactions in bacterial communities and their crucial roles in setting the stage for an evolutionary transition from anaerobic to aerobic lifestyles and subsequent environmental adaptation. These findings provide new insights into early bacterial evolution and their subsequent growth and adaptations to environments.

Biodegradation of Cyromazine by Mycobacterium sp. M15: Performance, Degradation Pathways, and Key Enzymes.

Cyromazine, a triazine insecticide, raises food safety concerns due to residues in vegetables like cowpeas. Microbial metabolism is key for pesticide elimination, but bacteria efficient in cyromazine degradation are limited, with uncharacterized enzymes. This study isolated a highly efficient cyromazine-degrading bacterium, Mycobacterium sp. M15, from a cowpea field. M15 utilized cyromazine as the sole carbon source for its growth and completely degraded 0.5 mM cyromazine within 24 h. The degradation pathway involved hydrolyzing cyromazine to N-cyclopropylammeline and further to N-cyclopropylammelide, with amino groups removed sequentially. The cyclopropylamine group in N-cyclopropionamide continued to hydrolyze to cyanuric acid. A protein, CriA, identified as an aminohydrolase in M15, degraded cyromazine to N-cyclopropylammeline. Using CriA reduced cyromazine residues on cowpea surfaces and completely degraded them in immersion solutions. These findings offer insights into cyromazine's microbial degradation mechanism and highlight the potential of cyromazine-degrading enzymes in enhancing food safety.

Engineering natural microbiomes toward enhanced bioremediation by microbiome modeling.

Engineering natural microbiomes for biotechnological applications remains challenging, as metabolic interactions within microbiomes are largely unknown, and practical principles and tools for microbiome engineering are still lacking. Here, we present a combinatory top-down and bottom-up framework to engineer natural microbiomes for the construction of function-enhanced synthetic microbiomes. We show that application of herbicide and herbicide-degrader inoculation drives a convergent succession of different natural microbiomes toward functional microbiomes (e.g., enhanced bioremediation of herbicide-contaminated soils). We develop a metabolic modeling pipeline, SuperCC, that can be used to document metabolic interactions within microbiomes and to simulate the performances of different microbiomes. Using SuperCC, we construct bioremediation-enhanced synthetic microbiomes based on 18 keystone species identified from natural microbiomes. Our results highlight the importance of metabolic interactions in shaping microbiome functions and provide practical guidance for engineering natural microbiomes.

Racialized and Immigrant Status and the Pursuit of Living Donor Kidney Transplant - a Canadian Cohort Study.

Introduction: Both immigrant and racialized status may be associated with the pursuit of living donor kidney transplant (LDKT). Methods: This study was a secondary analysis of a convenience cross-sectional sample of patients with kidney failure in Toronto, obtained from our "Comprehensive Psychosocial Research Data System" research database. The exposures included racialized, immigrant, and combined immigrant and racialized status (White nonimmigrant, racialized nonimmigrant, White immigrant and racialized immigrant). Outcomes include the following: (i) having spoken about LDKT with others, (ii) having a potential living donor (LD) identified, (iii) having allowed others to share the need for LDKT, (iv) having directly asked a potential donor to be tested, and (v) accept a hypothetical LDKT offer. We assessed the association between exposure and outcomes using univariable, and multivariable binary or multinominal logistic regression (reference: White or White nonimmigrant participants). Results: Of the 498 participants, 281 (56%) were immigrants; 142 (28%) were African, Caribbean, and Black (ACB); 123 (25%) were Asian; and 233 (47%) were White. Compared to White nonimmigrants, racialized immigrants (relative risk ratio [RRR]: 2.98; 95% confidence interval [CI]: 1.76-5.03) and racialized nonimmigrants (RRR: 2.84; 95% CI: 1.22-6.65) were more likely not to have spoken about LDKT with others (vs. having spoken or planning to do so). Both racialized immigrant (odds ratio [OR]: 4.07; 95% CI: 2.50-6.34), racialized nonimmigrants (OR: 2.68; 95% CI: 1.31-5.51) and White immigrants (OR: 2.68; 95% CI: 1.43-5.05) were more likely not to have a potential LD identified. Conclusion: Both racialized and immigrant status are associated with less readiness to pursue LDKT. Supporting patients to communicate their need for LDKT may improve equitable access to LDKT.

Sustained detoxification of 1,2-dichloroethane to ethylene by a symbiotic consortium containing Dehalococcoides species.

1,2-Dichloroethane (1,2-DCA) is a ubiquitous volatile halogenated organic pollutant in groundwater and soil, which poses a serious threat to the ecosystem and human health. Microbial reductive dechlorination has been recognized as an environmentally-friendly strategy for the remediation of sites contaminated with 1,2-DCA. In this study, we obtained an anaerobic microbiota derived from 1,2-DCA contaminated groundwater, which was able to sustainably convert 1,2-DCA into non-toxic ethylene with an average dechlorination rate of 30.70 ± 11.06 µM d-1 (N = 6). The microbial community profile demonstrated that the relative abundance of Dehalococcoides species increased from 0.53 ± 0.08% to 44.68 ± 3.61% in parallel with the dechlorination of 1,2-DCA. Quantitative PCR results showed that the Dehalococcoides species 16S rRNA gene increased from 2.40 ± 1.71 × 108 copies∙mL-1 culture to 4.07 ± 2.45 × 108 copies∙mL-1 culture after dechlorinating 110.69 ± 30.61 µmol of 1,2-DCA with a growth yield of 1.55 ± 0.93 × 108 cells per µmol Cl- released (N = 6), suggesting that Dehalococcoides species used 1,2-DCA for organohalide respiration to maintain cell growth. Notably, the relative abundances of Methanobacterium sp. (p = 0.0618) and Desulfovibrio sp. (p = 0.0001995) also increased significantly during the dechlorination of 1,2-DCA and were clustered in the same module with Dehalococcoides species in the co-occurrence network. These results hinted that Dehalococcoides species, the obligate organohalide-respiring bacterium, exhibited potential symbiotic relationships with Methanobacterium and Desulfovibrio species. This study illustrates the importance of microbial interactions within functional microbiota and provides a promising microbial resource for in situ bioremediation in sites contaminated with 1,2-DCA.

Site-specific ubiquitination of VDAC1 restricts its oligomerization and mitochondrial DNA release in liver fibrosis.

Mitochondrial DNA (mtDNA) released through protein oligomers, such as voltage-dependent anion channel 1 (VDAC1), triggers innate immune activation and thus contributes to liver fibrosis. Here, we investigated the role of Parkin, an important regulator of mitochondria, and its regulation of VDAC1-mediated mtDNA release in liver fibrosis. The circulating mitochondrial DNA (mtDNA) and protein levels of liver Parkin and VDAC1 were upregulated in patients with liver fibrosis. A 4-week CCl4 challenge induced release of mtDNA, activation of STING signaling, a decline in autophagy, and apoptosis in mouse livers, and the knockout of Parkin aggravated these effects. In addition, Parkin reduced mtDNA release and prevented VDAC1 oligomerization in a manner dependent on its E3 activity in hepatocytes. We found that site-specific ubiquitination of VDAC1 at lysine 53 by Parkin interrupted VDAC1 oligomerization and prevented mtDNA release into the cytoplasm under stress. The ubiquitination-defective VDAC1 K53R mutant predominantly formed oligomers that resisted suppression by Parkin. Hepatocytes expressing VDAC1 K53R exhibited mtDNA release and thus activated the STING signaling pathway in hepatic stellate cells, and this effect could not be abolished by Parkin. We propose that the ubiquitination of VDAC1 at a specific site by Parkin confers protection against liver fibrosis by interrupting VDAC1 oligomerization and mtDNA release.

Effects of Cigarette Smoke Exposure on the Gut Microbiota and Liver Transcriptome in Mice Reveal Gut-Liver Interactions.

Cigarette smoke exposure has a harmful impact on health and increases the risk of disease. However, studies on cigarette-smoke-induced adverse effects from the perspective of the gut-liver axis are lacking. In this study, we evaluated the adverse effects of cigarette smoke exposure on mice through physiological, biochemical, and histopathological analyses and explored cigarette-smoke-induced gut microbiota imbalance and changes in liver gene expression through a multiomics analysis. We demonstrated that cigarette smoke exposure caused abnormal physiological indices (including reduced body weight, blood lipids, and food intake) in mice, which also triggered liver injury and induced disorders of the gut microbiota and liver transcriptome (especially lipid metabolism). A significant correlation between intestinal bacterial abundance and the expression of lipid-metabolism-related genes was detected, suggesting the coordinated regulation of lipid metabolism by gut microbiota and liver metabolism. Specifically, Salmonella (harmful bacterium) was negatively and positively correlated with up- (such as Acsl3 and Me1) and downregulated genes (such as Angptl4, Cyp4a12a, and Plin5) involved in lipid metabolism, while Ligilactobacillus (beneficial bacterium) showed opposite trends with these genes. Our results clarified the key role of gut microbiota in liver damage and metabolism and improved the understanding of gut-liver interactions caused by cigarette smoke exposure.

Interspecies Metabolic Interactions in a Synergistic Consortium Drive Efficient Degradation of the Herbicide Bromoxynil Octanoate.

Microbial communities play vital roles in biogeochemical cycles, allowing biodegradation of a wide range of pollutants. Although many studies have shown the importance of interspecies interactions on activities of communities, fully elucidating the complex interactions in microbial communities is still challenging. Here, we isolated a consortium containing two bacterial strains (Acinetobacter sp. AG3 and Bacillus sp. R45), which could mineralize bromoxynil octanoate (BO) with higher efficiency than either strain individually. The BO degradation pathway by the synergistic consortium was elucidated, and interspecies interactions in the consortium were explored using genome-scale metabolic models (GSMMs). Modeling showed that growth and degradation enhancements were driven by metabolic interactions, such as syntrophic exchanges of small metabolites in the consortium. Besides, nutritional enhancers were predicted to improve BO degradation, which were tested experimentally. Overall, our results will enhance our understanding of microbial mineralization of BO by consortia and promote the application of microbial communities for bioremediation.

Genetic redundancy of 4-hydroxybenzoate 3-hydroxylase genes ensures the catabolic safety of Pigmentiphaga sp. H8 in 3-bromo-4-hydroxybenzoate-contaminated habitats.

Genetic redundancy is prevalent in organisms and plays important roles in the evolution of biodiversity and adaptation to environmental perturbation. However, selective advantages of genetic redundancy in overcoming metabolic disturbance due to structural analogues have received little attention. Here, functional divergence of the three 4-hydroxybenzoate 3-hydroxylase (PHBH) genes (phbh1~3) was found in Pigmentiphaga sp. strain H8. The genes phbh1/phbh2 were responsible for 3-bromo-4-hydroxybenzoate (3-Br-4-HB, an anthropogenic pollutant) catabolism, whereas phbh3 was primarily responsible for 4-hydroxybenzoate (4-HB, a natural intermediate of lignin) catabolism. 3-Br-4-HB inhibited 4-HB catabolism by competitively binding PHBH3 and was toxic to strain H8 cells especially at high concentrations. The existence of phbh1/phbh2 not only enabled strain H8 to utilize 3-Br-4-HB but also ensured the catabolic safety of 4-HB. Molecular docking and site-directed mutagenesis analyses revealed that Val199 and Phe384 of PHBH1/PHBH2 were required for the hydroxylation activity towards 3-Br-4-HB. Phylogenetic analysis indicated that phbh1 and phbh2 originated from a common ancestor and evolved specifically in strain H8 to adapt to 3-Br-4-HB-contaminated habitats, whereas phbh3 evolved independently. This study deepens our understanding of selective advantages of genetic redundancy in prokaryote's metabolic robustness and reveals the factors driving the divergent evolution of redundant genes in adaptation to environmental perturbation.

Comparative Genomics of Three Aspergillus Strains Reveals Insights into Endophytic Lifestyle and Endophyte-Induced Plant Growth Promotion.

Aspergillus includes both plant pathogenic and beneficial fungi. Although endophytes beneficial to plants have high potential for plant growth promotion and improving stress tolerance, studies on endophytic lifestyles and endophyte-plant interactions are still limited. Here, three endophytes belonging to Aspergillus, AS31, AS33, and AS42, were isolated. They could successfully colonize rice roots and significantly improved rice growth. The genomes of strains AS31, AS33, and AS42 were sequenced and compared with other Aspergillus species covering both pathogens and endophytes. The genomes of AS31, AS33, and AS42 were 36.8, 34.8, and 35.3 Mb, respectively. The endophytic genomes had more genes encoding carbohydrate-active enzymes (CAZymes) and small secreted proteins (SSPs) and secondary metabolism gene clusters involved in indole metabolism than the pathogens. In addition, these endophytes were able to improve Pi (phosphorus) accumulation and transport in rice by inducing the expression of Pi transport genes in rice. Specifically, inoculation with endophytes significantly increased Pi contents in roots at the early stage, while the Pi contents in inoculated shoots were significantly increased at the late stage. Our results not only provide important insights into endophyte-plant interactions but also provide strain and genome resources, paving the way for the agricultural application of Aspergillus endophytes.

Enhancing the Phytoremediation of Heavy Metals by Combining Hyperaccumulator and Heavy Metal-Resistant Plant Growth-Promoting Bacteria.

Heavy metals (HMs) have become a major environmental pollutant threatening ecosystems and human health. Although hyperaccumulators provide a viable alternative for the bioremediation of HMs, the potential of phytoremediation is often limited by the small biomass and slow growth rate of hyperaccumulators and HM toxicity to plants. Here, plant growth-promoting bacteria (PGPB)-assisted phytoremediation was used to enhance the phytoremediation of HM-contaminated soils. A PGPB with HM-tolerant (HMT-PGPB), Bacillus sp. PGP15 was isolated from the rhizosphere of a cadmium (Cd) hyperaccumulator, Solanum nigrum. Pot experiments demonstrated that inoculation with strain PGP15 could significantly increase the growth of S. nigrum. More importantly, strain PGP15 markedly improved Cd accumulation in S. nigrum while alleviating Cd-induced stress in S. nigrum. Specifically, PGP15 inoculation significantly decreased the contents of H2O2, MDA, and O 2 · - in S. nigrum, while the activities (per gram plant fresh weight) of SOD, APX, and CAT were significantly increased in the PGP15-inoculated plants compared with the control sample. These results suggested that the interactions between strain PGP15 and S. nigrum could overcome the limits of phytoremediation alone and highlighted the promising application potential of the PGPB-hyperaccumulator collaborative pattern in the bioremediation of HM-contaminated soils. Furthermore, the PGP15 genome was sequenced and compared with other strains to explore the mechanisms underlying plant growth promotion by HMT-PGPB. The results showed that core genes that define the fundamental metabolic capabilities of strain PGP15 might not be necessary for plant growth promotion. Meanwhile, PGP15-specific genes, including many transposable elements, played a crucial role in the adaptive evolution of HM resistance. Overall, our results improve the understanding of interactions between HMT-PGPB and plants and facilitate the application of HMT-PGPB in the phytoremediation of HM-contaminated soils.

Long-term effect of epigenetic modification in plant-microbe interactions: modification of DNA methylation induced by plant growth-promoting bacteria mediates promotion process.

BACKGROUND: Soil microbiomes are considered a cornerstone of the next green revolution, and plant growth-promoting bacteria (PGPB) are critical for microbiome engineering. However, taking plant-beneficial microorganisms from discovery to agricultural application remains challenging, as the mechanisms underlying the interactions between beneficial strains and plants in native soils are still largely unknown. Increasing numbers of studies have indicated that strains introduced to manipulate microbiomes are usually eliminated in soils, while others have reported that application of PGPB as inocula significantly improves plant growth. This contradiction suggests the need for a deeper understanding of the mechanisms underlying microbe-induced growth promotion. RESULTS: We showed PGPB-induced long-term plant growth promotion after elimination of the PGPB inoculum in soils and explored the three-way interactions among the exogenous inoculum, indigenous microbiome, and plant, which were key elements of the plant growth-promoting process. We found the rhizosphere microbiome assembly was mainly driven by plant development and root recruitments greatly attenuated the influence of inocula on the rhizosphere microbiome. Neither changes in the rhizosphere microbiome nor colonization of inocula in roots was necessary for plant growth promotion. In roots, modification of DNA methylation in response to inoculation affects gene expression related to PGPB-induced growth promotion, and disruptions of the inoculation-induced DNA methylation patterns greatly weakened the plant growth promotion. Together, our results showed PGPB-induced DNA methylation modifications in roots mediated the promotion process and these modifications remained functional after elimination of the inoculum from the microbiome. CONCLUSION: This study suggests a new mechanism in which PGPB affect DNA methylation in roots to promote plant growth, which provides important insights into microbiome-plant interactions and offers new strategies for plant microbiome engineering beyond the perspective of maintaining inoculum persistence in soils. Video abstract.

Comparative Genomic Analysis of Pseudoxanthomonas sp. X-1, a Bromoxynil Octanoate-Degrading Bacterium, and Its Related Type Strains.

Most Pseudoxanthomonas species described have been derived from water, plants, or contaminated soils. Here, a strain Pseudoxanthomonas sp. X-1 isolated from bromoxynil octanoate (BO)-contaminated soil is presented. Strain X-1 could degrade BO and produce bromoxynil. The optimal conditions for degradation of BO by strain X-1 were an initial BO concentration of 0.1 mM, 30 °C, pH 7, and Mn2+ concentration of 1.0 mM. The bacterial morphological, physiological, and biochemical characteristics of strain X-1 were described, which showed differences comparing with other related type strains. The genome of strain X-1 was sequenced, and a comparative genomic analysis of X-1 and other Pseudoxanthomonas species was conducted to explore the mechanisms underlying the differences among these strains. The genome of strain X-1 encodes 4160 genes, 4078 of which are protein-coding genes and 68 are RNA coding genes. Specifically, strain X-1 encodes enzymes belonging to 778 Enzyme Commission (EC) numbers, much more than those of other related strains, and 62 of them are unique. Eight genes coding esterase are detected in strain X-1 which leads to the ability of BO degradation. This study provides strain, enzyme, and genome resources for the microbial remediation of environments polluted by herbicide BO.

Bioaugmentation of Atrazine-Contaminated Soil With Paenarthrobacter sp. Strain AT-5 and Its Effect on the Soil Microbiome.

Atrazine, a triazine herbicide, is widely used around the world. The residue of atrazine due to its application in the fore-rotating crop maize has caused phytotoxicity to the following crop sweet potato in China. Bioaugmentation of atrazine-contaminated soil with atrazine-degrading strains is considered as the most potential method to remove atrazine from soil. Nevertheless, the feasibility of bioaugmentation and its effect on soil microbiome still need investigation. In this study, Paenarthrobacter sp. AT-5, an atrazine-degrading strain, was inoculated into agricultural soils contaminated with atrazine to investigate the bioaugmentation process and the reassembly of the soil microbiome. It was found that 95.9% of 5 mg kg-1 atrazine was removed from the soils when inoculated with strain AT-5 with 7 days, and the phytotoxicity of sweet potato caused by atrazine was significantly alleviated. qRT-PCR analysis revealed that the inoculated strain AT-5 survived well in the soils and maintained a relatively high abundance. The inoculation of strain AT-5 significantly affected the community structure of the soil microbiome, and the abundances of bacteria associated with atrazine degradation were improved.

Bacteria-driven phthalic acid ester biodegradation: Current status and emerging opportunities.

The extensive use of phthalic acid esters (PAEs) has led to their widespread distribution across various environments. As PAEs pose significant threats to human health, it is urgent to develop efficient strategies to eliminate them from environments. Bacteria-driven PAE biodegradation has been considered as an inexpensive yet effective strategy to restore the contaminated environments. Despite great advances in bacterial culturing and sequencing, the inherent complexity of indigenous microbial community hinders us to mechanistically understand in situ PAE biodegradation and efficiently harness the degrading power of bacteria. The synthetic microbial ecology provides us a simple and controllable model system to address this problem. In this review, we focus on the current progress of PAE biodegradation mediated by bacterial isolates and indigenous bacterial communities, and discuss the prospective of synthetic PAE-degrading bacterial communities in PAE biodegradation research. It is anticipated that the theories and approaches of synthetic microbial ecology will revolutionize the study of bacteria-driven PAE biodegradation and provide novel insights for developing effective bioremediation solutions.

Sustained remission of multi-line relapsed extranodal NK/T-cell lymphoma, nasal type, following sintilimab and chidamide: A case report.

INTRODUCTION: There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell - ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors. PATIENT CONCERNS: A 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010. DIAGNOSIS: positron emission tomography-computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014. INTERVENTIONS: The patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient's condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg. OUTCOMES: PET-CT imaging showed his lesions obtained remission after 8 months post-treatment. CONCLUSION: Thus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched.

Bioaugmentation of acetamiprid-contaminated soil with Pigmentiphaga sp. strain D-2 and its effect on the soil microbial community.

Bioaugmentation, a strategy based on microbiome engineering, has been proposed for bioremediation of pollutant-contaminated environments. However, the complex microbiome engineering processes for soil bioaugmentation, involving interactions among the exogenous inoculum, soil environment, and indigenous microbial microbiome, remain largely unknown. Acetamiprid is a widely used neonicotinoid insecticide which has caused environmental contaminations. Here, we used an acetamiprid-degrading strain, Pigmentiphaga sp. D-2, as inoculum to investigate the effects of bioaugmentation on the soil microbial community and the process of microbiome reassembly. The bioaugmentation treatment removed 94.8 and 92.5% of acetamiprid within 40 days from soils contaminated with 50 and 200 mg/kg acetamiprid, respectively. A decrease in bacterial richness and diversity was detected in bioaugmentation treatments, which later recovered with the removal of acetamiprid from soil. Moreover, the bioaugmentation treatment significantly influenced the bacterial community structure, whereas application of acetamiprid alone had little influence on the soil microbial community. Furthermore, the bioaugmentation treatment improved the growth of bacteria associated with acetamiprid degradation, and the inoculated and recruited taxa significantly influenced the keystone taxa of the indigenous microbiome, resulting in reassembly of the bacterial community yielding higher acetamiprid-degrading efficiency than that of the indigenous and acetamiprid-treated communities. Our results provide valuable insights into the mechanisms of microbiome engineering for bioaugmentation of acetamiprid-contaminated soils.

Deletion of the E3 ubiquitin ligase, Parkin, exacerbates chronic alcohol intake-induced cardiomyopathy through an Ambra1-dependent mechanism.

BACKGROUND AND PURPOSE: Chronic alcohol consumption contributes to contractile dysfunction and unfavourable geometric changes in myocardium, accompanied by altered autophagy and disturbed mitochondrial homeostasis. The E3 ubiquitin ligase Parkin encoded by PARK2 gene maintains a fundamental role in regulating mitophagy and mitochondrial homeostasis, although little is known of its role in the aetiology of alcoholic cardiomyopathy. Here we assessed the effects of Parkin deletion in chronic alcohol-evoked cardiotoxicity. EXPERIMENTAL APPROACH: Following alcohol (4%) or control diet intake for 8 weeks, adult male wild-type (WT) and PARK2 knockout (Parkin-/- ) mice were examined using echocardiography. Cardiomyocyte mechanical properties, morphology of myocardium, and mitochondrial damage were also evaluated. Autophagy and mitophagy levels were assessed by LC3B and GFP-LC3 puncta, and lysosome-dependent autophagic flux was scrutinized using GFP-mRFP-LC3 puncta and Bafilomycin A1 treatment. KEY RESULTS: Chronic alcohol exposure provoked unfavourable geometric changes in myocardium and led to mitochondrial dysfunction and cardiac contractile defects, effects further exacerbated by Parkin knockout. Chronic alcohol exposure provoked autophagy and PINK1/Parkin-mediated mitophagy without affecting lysosome-dependent autophagic flux, the effects of which were diminished by Parkin deletion. Parkin adenovirus infection in neonatal rat cardiomyocytes further increased autophagy and protected against alcohol-induced myocardial injury, effects blocked by siRNA for Ambra1 (Autophagy and Beclin1 regulator 1). Immunofluorescence staining and co-immunoprecipitation assays showed interactions between Parkin and Ambra1. CONCLUSIONS AND IMPLICATIONS: Parkin was essential for cardiac homeostasis in alcohol challenge, accompanied by increased autophagy/mitophagy and maintenance of mitochondrial integrity through its interaction with Ambra1.