Tumor suppressive function of IGF2BP1 in gastric cancer through decreasing MYC.

Gastric cancer is one of the most common causes of cancer-related death worldwide. The N6 -methyladenosine (m6 A) reader IGF2BP1 (insulin-like growth factor-2 mRNA binding protein 1) has been reported to promote cancer progression by stabilizing oncogenic mRNAs through its m6 A-binding activity in some tumors. However, the role of IGF2BP1 in gastric carcinogenesis remains unclear. In this study, we found that IGF2BP1 is significantly downregulated in tumor tissues from patients with gastric cancer. Lower expression of IGF2BP1 is associated with poor prognosis. Gastric cancer cell proliferation is suppressed by IGF2BP1 in an m6 A-dependent manner. Additionally, IGF2BP1 is able to significantly attenuate tumor growth of gastric cancer cells. Further m6 A sequencing and m6 A-RNA immunoprecipitation assays show that MYC (c-myc proto-oncogene) mRNA is a target transcript of IGF2BP1 in gastric cancer cells. IGF2BP1 inhibits gastric cancer cell proliferation by reducing the mRNA and protein expression of MYC. Mechanistically, IGF2BP1 promotes the degradation of MYC mRNA and inhibits its translation efficiency. Taken together, these data suggest that IGF2BP1 plays a tumor-suppressive role in gastric carcinogenesis by downregulating MYC in an m6 A-dependent manner, thereby making the IGF2BP1-MYC axis a potential target for gastric cancer treatment.

Transcription factor 7 like 2 promotes metastasis in hepatocellular carcinoma via NEDD9-mediated activation of AKT/mTOR signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system, and the exact mechanism of HCC is still unclear. Transcription factor 7 like 2 (TCF7L2) plays a pivotal role in cell proliferation and stemness maintenance. However, the exact mechanism of TCF7L2 in HCC remains unclear. METHODS: Clinical samples and public databases were used to analyze the expression and prognosis of TCF7L2 in HCC. The function of TCF7L2 in HCC was studied in vitro and in vivo. ChIP and luciferase assays were used to explore the molecular mechanism of TCF7L2. The relationship between TCF7L2 and NEDD9 was verified in HCC clinical samples by tissue microarrays. RESULTS: The expression of TCF7L2 was upregulated in HCC, and high expression of TCF7L2 was associated with poor prognosis of HCC patients. Overexpression of TCF7L2 promoted the metastasis of HCC in vitro and in vivo, while Knockdown of TCF7L2 showed the opposite effect. Mechanically, TCF7L2 activated neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) transcription by binding to the -1522/-1509 site of the NEDD9 promoter region, thereby increasing the phosphorylation levels of AKT and mTOR. The combination of TCF7L2 and NEDD9 could distinguish the survival of HCC patients. CONCLUSIONS: This study demonstrated that TCF7L2 promotes HCC metastasis by activating AKT/mTOR pathway in a NEDD9-dependent manner, suggesting that potential of TCF7L2 and NEDD9 as prognostic markers and therapeutic targets for HCC.

Revealing assembly mechanisms of algal communities in aquatic microniches: Shifts in diversity patterns, microbial interactions and stability along nutrient gradients.

Algal blooms threaten water quality and ecosystem stability in aquatic habitats globally, yet dynamics regulating phytoplankton community assembly, the basis of blooms, remain poorly characterized in small water bodies. Here, we employed high-throughput sequencing to analyze drivers structuring phytoplankton across a trophic gradient of 10 small water bodies over 12 consecutive months. Cyanobacteria and Chlorophyta were identified as potential seed banks priming blooms. Temporal variation in community composition was muted in nutrient-limited waters given Cyanobacteria dominance. Environmental factors and interspecific relationships jointly governed temporal phytoplankton dynamics. Phytoplankton, exhibiting greater sensitivity, responded more rapidly than bacterioplankton to environmental and biological fluctuations. This research provides a robust bench mark characterizing planktonic successional trajectories across small water bodies varying in trophic status. Results reinforce ecological mechanisms underpinning biological control strategies to mitigate algal proliferation and inform water quality management of these ubiquitous aquatic ecosystems.

Enhanced nitrogen removal of the anaerobic ammonia oxidation process by coupling with an efficient nitrate reducing bacterium (Bacillus velezensis M3-1).

Bacillus velezensis M3-1 strain isolated from the sediment of Myriophyllum aquatium constructed wetlands was found to efficiently convert NO3--N to NO2--N, and the requirements for carbon source addition were not very rigorous. This work demonstrates, for the first time, the feasibility of using the synergy of anammox and Bacillus velezensis M3-1 microorganisms for nitrogen removal. In this study, the possibility of M3-1 that converted NO3--N produced by anammox to NO2--N was verified in an anaerobic reactor. The NO3--N reduction ability of M3-1 and denitrifying bacteria in coupling system was investigated under different C/N conditions, and it was found that M3-1 used carbon sources preferentially over denitrifying bacteria. By adjusting the ratio of NH4+-N to NO2--N, it was found that the NO2--N converted from NO3--N by M3-1 participated in the original anammox.The nitrogen removal efficacy (NRE) of the coupled system was increased by 12.1%, compared to the control group anammox system at C/N = 2:1. Functional gene indicated that it might be a nitrate reducing bacterium.This study shows that the nitrate reduction rate achieved by the Bacillus velezensis M3-1 can be high enough for removing nitrate produced by anammox process, which would enable improve nitrogen removal from wastewater.

Insulin-induced gene 2 protects against hepatic ischemia-reperfusion injury via metabolic remodeling.

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.

Production of biochar from squeezed liquid of fruit and vegetable waste: Impacts on soil N2O emission and microbial community.

The squeezed liquid from fruit and vegetable waste (LW) presents a unique wastewater challenge, marked by recalcitrance in treatment and amplified design risks with the application of conventional processes. Following coagulation of the squeezed liquid, the majority of particulate matter precipitates. The resulting precipitated floc (LWF) is reclaimed and subsequently utilized for the synthesis of biochar. The present study primarily explores the viability of repurposing LWF as biochar to enhance soil quality and mitigate N2O emissions. Findings indicate that the introduction of a 2% proportion of LWFB led to a remarkable 99.5% reduction in total N2O emissions in contrast to LWF. Concurrently, LWFB substantially enhanced nutrients content by elevating soil organic carbon (SOC) and nitrogen levels. Utilizing high-throughput sequencing in conjunction with qPCR, the investigation unveiled that the porous structure and substantial specific surface area of LWFB potentially fostered microbial adhesion and heightened diversity within the soil microbial community. Furthermore, LWFB notably diminished the relative abundance of AOB (Nitrosospira, Nitrosomonas), and NOB (Candidatus_Nitrotoga), thereby curbing the conversion of NH4+ into NO3-. The pronounced elevation in nosZ abundance implies that LWFB holds the potential to mitigate N2O emissions through a conversion to N2.

The predictive value of the modified AFP model for liver transplantation outcomes in multinodular hepatocellular carcinoma patients.

BACKGROUND: There is a lack of studies focusing on the benefit of liver transplantation (LT) in hepatocellular carcinoma (HCC) patients with > 3 tumors. This study aims to establish a model to effectively predict overall survival in Chinese HCC patients with multiple tumors (> 3 tumors) who undergo LT. METHODS: This retrospective study included 434 HCC liver transplant recipients from the China Liver Transplant Registry. All HCC patients had more than 3 tumor nodules. Three selection criteria systems (i.e., AFP, Metroticket 2.0, and Up-to-7) were compared regarding the prediction of HCC recurrence. The modified AFP model was established by univariate and multivariate competing risk analyses. RESULTS: The AFP score 2 and the AFP score ≥ 3 groups had 5-year recurrence rates of 19.6% and 40.5% in our cohort. The prediction of HCC recurrence based on the AFP model was associated with a c-statistic of 0.606, which was superior to the Up-to-7 and Metroticket 2.0 models. AFP level > 1000 ng/mL, largest tumor size ≥ 8 cm, vascular invasion, and MELD score ≥ 15 were associated with overall survival. The 5-year survival rate in the modified AFP score 0 group was 71.7%. CONCLUSIONS: The AFP model is superior in predicting tumor recurrence in HCC patients with > 3 tumors prior to LT. With the modified AFP model, patients likely to derive sufficient benefit from LT can be identified.

Transcriptomics Insights into Phosphorus Stress Response of Myriophyllum aquaticum.

Through excellent absorption and transformation, the macrophyte Myriophyllum (M.) aquaticum can considerably remove phosphorus from wastewater. The results of changes in growth rate, chlorophyll content, and roots number and length showed that M. aquaticum could cope better with high phosphorus stress compared with low phosphorus stress. Transcriptome and differentially expressed genes (DEGs) analyses revealed that, when exposed to phosphorus stresses at various concentrations, the roots were more active than the leaves, with more DEGs regulated. M. aquaticum also showed different gene expression and pathway regulatory patterns when exposed to low phosphorus and high phosphorus stresses. M. aquaticum's capacity to cope with phosphorus stress was maybe due to its improved ability to regulate metabolic pathways such as photosynthesis, oxidative stress reduction, phosphorus metabolism, signal transduction, secondary metabolites biosynthesis, and energy metabolism. In general, M. aquaticum has a complex and interconnected regulatory network that deals efficiently with phosphorus stress to varying degrees. This is the first time that the mechanisms of M. aquaticum in sustaining phosphorus stress have been fully examined at the transcriptome level using high-throughput sequencing analysis, which may indicate the direction of follow-up research and have some guiding value for its future applications.

Strategies for energy conversion from sludge to methane through pretreatment coupled anaerobic digestion: Potential energy loss or gain.

Anaerobic digestion (AD) of wasted activated sludge from wastewater plants is recognized as an effective method to reclaim energy in the form of methane. AD performance has been enhanced by coupling various pretreatments that impact energy conversion from sludge. This paper mainly reviewed the development of pretreatments based on different technologies reported in recent years and evaluated their energy benefit. Significant increases in methane yield are generally obtained in AD with pretreatments demanding energy input, including thermal- and ultrasound-based methods. However, these energy-intense pretreatments usually gained negative energy benefit that the increase in methane yield consumed extra energy input. The unbalanced relationship counts against the goal of energy reclamation from sludge. Combined pretreatment consisting of multiple technologies normally outcompetes the single pretreatment, and the combination of energy-intense methods and chemicals potentially reduces energy input and simultaneously ensure high methane yield. For determining whether the energy reclamation from sludge via AD contribute to mitigating global warming, integrating greenhouse gas emission into the evaluation system of pretreated AD is further warranted.

Purification performance from bypass ecological treatment systems treating WWTPs effluents and improvement of water quality in receiving rivers: A case study in southern China.

Effluents from wastewater treatment plants (WWTPs) is the main source of pollution in rivers in developing countries. In this case study, three bypass ecological treatment systems along urban rivers achieved high removal efficiencies for chemical oxygen demand (COD; 55.7-64.0%), ammonium N (NH4+-N; 63.1-89.4%) and total phosphorous (TP; 27.6-76.7%). 16 S rRNA gene sequencing analysis confirmed that Proteobacteria was the main bacterial phylum (44.4%) in the ecological treatment system, and members were enriched significantly in the non-aeration area (59.3%). The relative abundance of Nitrospirae was highest in the inflow area (25.0%), but restrained in the non-aeration area (5.7%). 18 S rRNA gene annotation results indicated that phylum Rotifer was gradually inhibited with the direction of water flow and diffusion, while phylum Rhodophyta displayed the opposite trend. After implementation of bypass ecological treatment systems, receiving rivers were improved significantly from Grade Ⅴ to Ⅳ, and the biodiversity of zooplankton, zoobenthos and fish communities was greatly improved.

Fast start-up of anammox process: Effects of extracellular polymeric substances addition on performance, granule properties, and bacterial community structure.

The slow startup is the major obstacle to the application of anaerobic ammonium oxidation (anammox) process in mainstream wastewater treatment. Extracellular polymeric substances (EPS) are one potential resource for stable anammox reactor operation. Response surface analysis was used to optimize the specific anammox activity (SAA) with the addition of EPS; SAA was maximum at a temperature of 35 °C and the EPS concentration of 4 mg/L. By comparing the nitrogen removal of anammox reactors with no EPS (R0), immobilized EPS (EPS-alginate beads) (R1), and liquid EPS (R2), we found that EPS-alginate beads significantly speed up the startup of anammox process and enable the start time to be shortened from 31 to 19 days. As a result of the higher MLVSS content, higher zeta potential, and lower SVI30, anammox granules of R1 exhibited a stronger capacity to aggregate. Moreover, EPS extracted from R1 had higher flocculation efficiencies than EPS derived from R0 and R2. Phylogenetic analysis of 16S rRNA genes revealed that the main anammox species in R1 is Kuenenia taxon. To clarify the relative significance of stochastic vs deterministic processes in the anammox community, neutral model and network analysis are employed. In R1, community assembly became more deterministic and stable than in other cultures. Our results show that EPS might inhibit heterotrophic denitrification and thereby promote anammox activity. This study suggested a quick start-up strategy for the anammox process based on resource recovery, which is helpful for environmentally sustainable and energy-efficient wastewater treatment.

Microbial community structure analyses and cultivable denitrifier isolation of Myriophyllum aquaticum constructed wetland under low C/N ratio.

With the rapid expansion of livestock production, the amount of livestock wastewater accumulated rapidly. Lack of biodegradable organic matter makes denitrification of livestock wastewater after anaerobic digestion more difficult. In this study, Myriophyllum aquaticum constructed wetlands (CWs) with efficient nitrogen removal performance were established under different carbon/nitrogen (C/N) ratios. Analysis of community composition reveals the change of M. aquaticum CWs in microbial community structure with C/N ratios. The proportion of Proteobacteria which is one of the dominant phyla among denitrifier communities increased significantly under low C/N ratio conditions. Besides, to obtain cultivable denitrifier that could be added into CWs in situ, 33 strains belonging to phylum Proteobacteria were isolated from efficient M. aquaticum CWs, while the best-performing denitrification strain M3-1 was identified as Bacillus velezensis JT3-1 (GenBank No. CP032506.1). Redundancy analysis and quadratic models showed that C/N ratio had significant effects on disposal of nitrate (NO3--N) and the strains isolated could perform well in denitrification when C/N ratio is relatively low. In addition, they have relatively wide ranges of carbon sources, temperature and a high NO3- removal rate of 9.12 mg/(L·hr) at elevated concentrations of 800 mg/L nitrate. Thus, strains isolated from M. aquaticum CWs with low C/N ratio have a practical application value in the treatment of nitrate-containing wastewater. These denitrifying bacteria could be added to CWs to enhance nitrogen removal efficiency of CWs for livestock wastewater with low C/N ratio in the future.

When immunotherapy meets liver transplantation for hepatocellular carcinoma: A bumpy but promising road.

Liver transplantation (LT) is a highly curative therapy for patients with hepatocellular carcinoma (HCC). However, due to the shortage of donor livers and rapid progression of HCC, a majority of patients are dropped out from the waitlist. Recently, immunotherapy has shown great promise in the treatment of advanced HCC. However, the use of immunotherapy is limited in LT mainly due to the potentially increasing risk of graft rejection. One of the main challenges for researchers is the protection of donor graft from an immunotherapy-boosted immune response mounted by the host. Besides, the safety, availability, and costs of immunotherapy are other challenges that need to be addressed. Here, we reviewed the literature involving patients who received immunotherapy prior to transplant to avoid waitlist dropouts and following transplantation to prevent the progression of tumor recurrence and metastasis. Statistically, the incidence of rejection was 25.0% pre-transplant and 18.5% post-transplant. Based on the review of these clinical studies, we can conclude that conducting clinical trials on the safety and efficacy of currently available immunotherapy drugs and identifying novel immunotherapy targets through extensive research may be promising for patients who do not meet the selection criteria for LT and who experience post-transplant recurrence. To date, the clinical experience on the use of immunotherapy before or after LT comes from individual case studies. Although some of the reported results are promising, they are not sufficient to support the standardized use of immunotherapy in clinical practice.

E2F7 promotes mammalian target of rapamycin inhibitor resistance in hepatocellular carcinoma after liver transplantation.

The mammalian target of rapamycin (mTOR) pathway is frequently deregulated and has critical roles in cancer progression. mTOR inhibitor has been widely used in several kinds of cancers and is strongly recommended in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). However, the poor response to mTOR inhibitors due to resistance remains a challenge. Hypoxia-associated resistance limits the therapeutic efficacy of targeted drugs. The present study established models of HCC clinical samples and cell lines resistance to mTOR inhibitor sirolimus and screened out E2F7 as a candidate gene induced by hypoxia and promoting sirolimus resistance. E2F7 suppressed mTOR complex 1 via directly binding to the promoter of the TSC1 gene and stabilizes hypoxia-inducible factor-1α activating its downstream genes, which are responsible for E2F7-dependent mTOR inhibitor resistance. Clinically, low E2F7 expression could be an effective biomarker for recommending patients with HCC for anti-mTOR-based therapies after LT. Targeting E2F7 synergistically inhibited HCC growth with sirolimus in vivo. E2F7 is a promising target to reverse mTOR inhibition resistance. Collectively, our study points to a role for E2F7 in promoting mTOR inhibitor resistance in HCC and emphasizes its potential clinical significance in patients with HCC after LT.

Liver transplantation in patients with liver failure: Twenty years of experience from China.

Liver transplantation (LT) is the only effective method of treating end-stage liver disease, such as various types of liver failure. China has the largest number of patients with hepatitis B virus-related disease, which is also the main cause of liver failure. From the first LT performed in 1977, and especially over the past two decades, LT has experienced rapid development as a result of continuous research and innovation in China. China performs the second-highest number of LTs every year worldwide, and the quality of LT continues to improve. Starting January 1, 2015, all donor's livers have been from deceased donors and familial donors. Thus, China entered into a new era of LT. However, LT is still a challenging procedure in China. In this review, we introduced the brief history of LT in China, the epidemiology, aetiology and clinical outcomes of LT for liver failure in China and summarized the experience of LT from Chinese LT surgeons and scholars. The future perspectives of LT were also discussed, and it is expected that China's LT research could be further integrated elsewhere in the world.

Impact of influent strengths on nitrous oxide emission and its molecular mechanism in constructed wetlands treating swine wastewater.

Constructed wetlands (CWs) can remove nitrogen (N) through plant assimilation and microbial nitrification and denitrification, while it also releases large greenhouse gas nitrous oxide (N2O) into the atmosphere. However, N2O emissions and the underlying microbial mechanisms of CWs when treating high-strength wastewater have not been systematically surveyed. Here, the effect of three influent strengths on N2O emissions in a pilot-scale CW treatment of swine wastewater was determined and the underlying microbial mechanisms were explored. The results showed that the removal rates of ammonium (NH4+) and total nitrogen (TN) increased significantly with the increasing influent strengths, however, the ratio of N2O emission/TN removal rose by 1.5 times at the same time. Quantitation of microorganisms responsible for N-cycle in the sediment indicated that the abundance of ammonia-oxidizing bacteria (AOB) in high influent strengths (COD, 962.38 ± 3.05 mg/L; NH4+, 317.89 ± 4.24 mg/L) was 51.6-fold compared with that in low influent strengths (COD, 516.94 ± 4.18 mg/L; NH4+, 100.65 ± 2.65), and AOB gradually replaced ammonia-oxidizing archaea (AOA) to dominate ammonia oxidizers. Structural equation models demonstrated that NO2- accumulations promoted the ratio of AOB/AOA, which further led to an increase in the ratio of N2O emission/TN removal. It is worth noting both the N removal rates and N2O emissions increased with the increasing influent strength. To obtain reduced N2O emissions, pretreatment technology for strength reduction should be supplemented before high-strength wastewater enters the CWs. This study may shed new light on the sustainable operation and application of CWs.

Oxidative stress of Microcystis aeruginosa induced by algicidal bacterium Stenotrophomonas sp. KT48.

Cyanobacterial harmful algal blooms are a worldwide problem with substantial adverse effects on the aquatic environment as well as human health. Among the multiple physicochemical and biotic approaches, algicidal bacterium is one of the most promising and eco-friendly ways to control bloom expansion. In this study, Stenotrophomonas sp. KT48 isolated from the pond where cyanobacterial blooms occurred exhibited a strong inhibitory effect on Microcystis aeruginosa. However, the algicidal performance and mechanisms of Stenotrophomonas sp. remain under-documented. To explore the algicidal performance and physiological response againt M. aeruginosa, further works were implemented here. Our results indicated that the algicidal rate of strain KT48 cultured in 1/8 LB medium supplemented with 0.3% starch or glucose was about 30% higher than that in 1/8 LB medium. Strain KT48 culture, cell-free filtrate, and cells re-suspended were inoculated into the M. aeruginosa culture, and the Chl-a content was determined. Those results indicated that the algicidal activity of cells re-suspended was far higher than that of cell-free filtrate and culture. Thus, strain KT48 exhibited algicidal activity mainly through direct attacking M. aeruginosa rather than excretion of algicides. Furthermore, strain KT48 led to an increase in cellular reactive oxygen species (ROS) and caused lipid peroxidation as supported by the increase in malondialdehyde (MDA) levels. The ROS and MDA levels in algal cells treated with strain KT48 cells re-suspended were about 3.23-fold and 2.80-fold higher than those of untreated algal cells on day 11. And a further inhibition to the antioxidant system is suggested by a sharp decrease in the superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities. In addition, we also observed that the morphology of most algal cells changed from integrity to break. This study not only indicated strain KT48 with strong algicidal activity, but also explored the underlying algicidal mechanisms to provide a source of bacterial agent for the biocontrol of cyanobacterial blooms. KEY POINTS: • Strain KT48 exhibited strong algicidal activity mainly through direct attacking M. aeruginosa. • The addition of glucose could enhance the algicidal rate of strain KT48 by about 30%. • Strain KT48 led to an increase in cellular reactive oxygen species (ROS) level that causes membrane damage as supported by the increase in malondialdehyde (MDA) levels.

Ecological selection of bacterial taxa with larger genome sizes in response to polycyclic aromatic hydrocarbons stress.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous priority pollutants that cause great damage to the natural environment and health. Average genome size in a community is critical for shedding light on microbiome's functional response to pollution stress within an environment. Here, microcosms under different concentrations were performed to evaluate the selection of PAHs stress on the average genome size in a community. We found the distinct communities of significantly larger genome size with the increase of PAHs concentration gradients in soils, and consistent trends were discovered in soils at different latitudes. The abundance of Proteobacteria and Deinococcus-Thermus with relatively larger genomes increased along with PAHs stress and well adapted to polluted environments. In contrast, the abundance of Patescibacteria with a highly streamlined and smaller genome decreased, implying complex interactions between environmental selection and functional fitness resulted in bacteria with larger genomes becoming more abundant. Moreover, we confirmed the increased capacity for horizontal transfer of degrading genes between communities by showing an increased connection number per node positively related to the nidA gene along the concentration gradients in the co-occurrence network. Our findings suggest PAHs tend to select bacterial taxa with larger genome sizes, with significant consequences for community stability and potential biodegradation strategies.

USP22 promotes hypoxia-induced hepatocellular carcinoma stemness by a HIF1α/USP22 positive feedback loop upon TP53 inactivation.

OBJECTIVE: We aimed to elucidate the mutual regulation mechanism of ubiquitin-specific protease 22 (USP22) and hypoxia inducible factor-1α (HIF1α), and the mechanism they promote the stemness of hepatocellular carcinoma (HCC) cells under hypoxic conditions. DESIGN: Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were established to detect the stemness of HCC cells. Immunoprecipitation, ubiquitination assay and chromatin immunoprecipitation assay were used to elucidate the mutual regulation mechanism of USP22 and HIF1α. HCC patient samples and The Cancer Genome Atlas data were used to demonstrate the clinical significance. In vivo USP22-targeting experiment was performed in mice bearing HCC. RESULTS: USP22 promotes hypoxia-induced HCC stemness and glycolysis by deubiquitinating and stabilising HIF1α. As direct target genes of HIF1α, USP22 and TP53 can be transcriptionally upregulated by HIF1α under hypoxic conditions. In TP53 wild-type HCC cells, HIF1α induced TP53-mediated inhibition of HIF1α-induced USP22 upregulation. In TP53-mutant HCC cells, USP22 and HIF1α formed a positive feedback loop and promote the stemness of HCC. HCC patients with a loss-of-function mutation at TP53 and high USP22 and/or HIF1α expression tend to have a worse prognosis. The USP22-targeting lipopolyplexes caused high tumour inhibition and high sorafenib sensitivity in mice bearing HCC. CONCLUSION: USP22 promotes hypoxia-induced HCC stemness by a HIF1α/USP22 positive feedback loop on TP53 inactivation. USP22 is a promising target for the HCC therapy.

Paenibacillus polymyxa biofertilizer application in a tea plantation reduces soil N2O by changing denitrifier communities.

Increasing the use of nitrogen fertilizers in tea orchards has led to intense nitrous oxide (N2O) emissions. Foliar application of Paenibacillus polymyxa biofertilizer has been proven to be beneficial for organic tea production. In this study, tea yield and quality were significantly improved after application of P. polymyxa biofertilizer compared with the control but were not significantly different from chemical fertilizer treatments. However, the average N2O fluxes in tea fields treated with chemical fertilizers and biofertilizers (225 kg N·ha-1·year-1 for both) were 50.6-973.7 and 0.6-29.1 times higher than those in the control treatment, respectively. Pot experiments conducted to explore the mechanism of N2O reduction induced by P. polymyxa biofertilizer showed that applying P. polymyxa in addition to urea could reduce N2O fluxes by 36.5%-73.1%. Quantitative PCR analysis suggested that a significant increase in the quantity of nirK and nosZ genes was linked to the reduction of N2O, and high-throughput sequencing of nosZ revealed active and potentially efficient denitrifiers in different treatments. Our findings suggest that P. polymyxa biofertilizer is in line with the requirements of modern agriculture, which aims to increase product yield and quality while reducing negative environmental impacts.