Hepatocyte-specific METTL3 ablation by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), resulted in acute liver failure (ALF) and postnatal lethality.

AIM: In 2019, to examine the functions of METTL3 in liver and underlying mechanisms, we generated mice with hepatocyte-specific METTL3 homozygous knockout (METTL3Δhep) by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT) or Alb-Cre mice (JAX), respectively. In this study, we explored the potential reasons why hepatocyte-specific METTL3 homozygous disruption by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), resulted in acute liver failure (ALF) and then postnatal lethality. MAIN METHODS: Mice with hepatocyte-specific METTL3 knockout were generated by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT; Strain No. T003814) purchased from the GemPharmatech Co., Ltd., (Nanjing, China) or with Alb-Cre mice (JAX; Strain No. 003574) obtained from The Jackson Laboratory, followed by combined-phenotype analysis. The publicly available RNA-sequencing data deposited in the NCBI Gene Expression Omnibus (GEO) database under the accession No.: GSE198512 (postnatal lethality), GSE197800 (postnatal survival) and GSE176113 (postnatal survival) were mined to explore the potential reasons why hepatocyte-specific METTL3 homozygous deletion by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), leads to ALF and then postnatal lethality. KEY FINDINGS: Firstly, we observed that hepatocyte-specific METTL3 homozygous deficiency by Alb-iCre mice (GPT) or by Alb-Cre mice (JAX) caused liver injury, abnormal lipid accumulation and apoptosis. Secondly, we are surprised to find that hepatocyte-specific METTL3 homozygous deletion by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), led to ALF and then postnatal lethality. Our findings clearly demonstrated that METTL3Δhep mice (GPT), which are about to die, exhibited the severe destruction of liver histological structure, suggesting that METTL3Δhep mice (GPT) nearly lose normal liver function, which subsequently contributes to ALF, followed by postnatal lethality. Finally, we unexpectedly found that as the compensatory growth responses of hepatocytes to liver injury induced by METTL3Δhep (GPT), the proliferation of METTL3Δhep hepatocytes (GPT), unlike METTL3Δhep hepatocytes (JAX), was not evidenced by the significant increase of Ki67-positive hepatocytes, not accompanied by upregulation of cell-cycle-related genes. Moreover, GO analysis revealed that upregulated genes in METTL3Δhep livers (GPT), unlike METTL3Δhep livers (JAX), are not functionally enriched in terms associated with cell cycle, cell division, mitosis, microtubule cytoskeleton organization, spindle organization, chromatin segregation and organization, and nuclear division, consistent with the loss of compensatory proliferation of METTL3Δhep hepatocytes (GPT) observed in vivo. Thus, obviously, the loss of the compensatory growth capacity of METTL3Δhep hepatocytes (GPT) in response to liver injury might contribute to, at least partially, ALF and subsequently postnatal lethality of METTL3Δhep mice (GPT). SIGNIFICANCE: These findings from this study and other labs provide strong evidence that these phenotypes (i.e., ALF and postnatal lethality) of METTL3Δhep mice (GPT) might be not the real functions of METTL3, and closely related with Alb-iCre mice (GPT), suggesting that we should remind researchers to use Alb-iCre mice (GPT) with caution to knockout gene in hepatocytes in vivo.

Continuous renal replacement therapy improves indicators and short-term survival in people with AIDS manifesting sepsis and acute kidney injury.

Acquired immune deficiency syndrome (AIDS) is susceptible to numerous complications such as sepsis and acute kidney injury (AKI), leading to adverse outcomes. Continuous renal replacement therapy (CRRT) is becoming increasingly popular in the treatment of sepsis and AKI. This study aimed to verify the effectiveness of CRRT in the treatment of AIDS with sepsis and AKI, to provide new directions for the treatment of severe AIDS. Data of 74 people with AIDS, sepsis and AKI were collected. They were divided into CRRT and non-CRRT groups. There was no difference in indicators between the two groups at admission. Vital signs, PH, serum potassium, renal function, blood lactate, APACHE II score, and SOFA score in CRRT group demonstrated significant improvements over those in the non-CRRT group both 24 and 72 hours after admission (P＜0.05). Level of Interleukin 6 and procalcitonin declined more significantly in CRRT group 72 hours after admission (P＜0.05). CRRT group had a higher 28-day survival rate (P＜0.05). CRRT improves the clinical indicators and increases the short-term survival rate of people with AIDS, sepsis and AKI.

lncRNA NEAT1 mediates LPS-induced pyroptosis of BEAS-2B cells via targeting miR-26a-5p/ROCK1 axis.

Acute lung injury (ALI) is an adverse disease of the respiratory system, and one of its prevalent causes is sepsis induction. Cell pyroptosis facilitates the progression of ALI and lncRNAs play critical roles in ALI. Thus, this research seeks to investigate the specific mechanism of NEAT1 in sepsis-ALI.BEAS-2B cells were exposed to lipopolysaccharide (LPS) to construct a cell model of sepsis-induced ALI. The gene and protein expression were assessed using qRT-PCR and western blot. Cell viability was identified by CCK-8. Cell death was discovered using PI staining. The secretion of IL-1ß and IL-18 was examined using ELISA. The interconnections among NEAT1, miR-26a-5p, and ROCK1 were confirmed using starbase, luciferase assay, and RIP.LPS treatment augmented NEAT1 and ROCK1 levels while mitigating miR-26a-5p level in BEAS-2B cells. Additionally, LPS treatment facilitated cell death and cell pyroptosis, whereas NEAT1 silencing could reverse these effects in BEAS-2B cells. Mechanistically, NEAT1 positively mediated ROCK1 expression by targeting miR-26a-5p. Furthermore, miR-26a-5p inhibitor offset NEAT1 depletion-mediated suppressive effects on cell death and cell pyroptosis. ROCK1 upregulation decreased the inhibitory impacts produced by miR-26a-5p overexpression on cell death and cell pyroptosis. Our outcomes demonstrated NEAT1 could reinforce LPS-induced cell death and cell pyroptosis by repressing the miR-26a-5p/ROCK1 axis, thereby worsening ALI caused by sepsis. Our data indicated NEAT1, miR-26a-5p, and ROCK1 might be biomarkers and target genes for relieving sepsis-induced ALI.

Volatile sulfur compound emissions and health risk assessment from an A2/O wastewater treatment plant.

Anoxic/anaerobic/oxic (A2/O) wastewater treatment has emerged as a major process for treatment of domestic wastewater. One of the issues with wastewater treatment plants (WWTPs) is that volatile sulfur compounds (VSCs) are discharged from them and pose numerous health risks. This study characterized VSC emissions at the water-air interface and concentrations of ambient air exposure from different treatment units in an A2/O WWTP. AERMOD modeling was used to simulate the atmospheric behaviors of discharged VSCs. Results demonstrated that VSC emission fluxes and exposure concentrations had followed a descending order of pretreatment>biological treatment>advanced treatment. Emissions were affected by sulfate concentrations and chemical oxygen demand in the wastewater, and control strategies based on these values were proposed. The AERMOD results indicated that the majority of the total hydrogen sulfide (87%) and methyl mercaptan (65%) emissions came from the primary sedimentation tank, while the majority of dimethyl sulfide (81%), carbon disulfide (84%), and dimethyl disulfide (93%) were emitted from the oxic area. MT and DMS were the main odorous components of the VSCs in ambient air based on the indicator of odor activity values. Noncancer health risks, determined by having a hazard quotient >1, of the measured VSCs were beyond acceptable limits. Overall, efforts should be made to minimize noncancer health risks as individuals are exposed to VSCs not only in treatment units but also in areas surrounding WWTPs.

Emission characteristics of odorous volatile sulfur compound from a full-scale sequencing batch reactor wastewater treatment plant.

Volatile sulfur compounds (VSCs) generated and discharged as air pollutants from wastewater treatment plants (WWTPs) pose a threat to human health and the environment. This study characterized VSC emissions from a full-scale sequencing batch reactor (SBR) WWTP at the water-air interface for one year. Results demonstrated that higher ambient temperatures and aeration contributed significantly to VSC emissions as the highest emissions occurred over summer during the feeding synchronous aeration period. VSC emissions were related to chemical oxygen demand and sulfate concentrations in wastewater, and empirical formulas based on these values were proposed that can be used to model VSC emission fluxes from SBR WWTP. VSC emission factors (µg·ton-1 wastewater) throughout the SBR treatment process were: 361 ± 101 hydrogen sulfide (H2S), 82 ± 76 methyl mercaptan (MT), 61 ± 31 dimethyl sulfide, 17 ± 5 carbon disulfide, and 46 ± 24 dimethyl disulfide. H2S and MT were the dominant odors released. Findings from this study may be applicable for calculating VSC emissions during SBR wastewater treatment stages, and may be beneficial for determining methods and strategies to reduce VSCs.

Emission characteristics and assessment of odors from sludge anaerobic digestion with thermal hydrolysis pretreatment in a wastewater treatment plant.

Anaerobic digestion (AD) with thermal hydrolysis pre-treatment (THP) is an effective sludge treatment method which provides several advantages such as enhanced biogas formation and fertilizer production. The main limitation to THP-AD is that hazardous odors, including NH3 and volatile sulfur compounds (VSCs), are emitted during the sludge treatment process. In order to develop strategies to eliminate odors, it is necessary to identify the key odors and emissions sites. This study identified production of NH3 (741.60 g·dry sludge t-1) and VSCs (277.27 g·dry sludge t-1) during sludge AD after THP, and measured emissions in each of the THP-AD sludge treatment sites. Odor intensity, odor active values, permissible concentration-time weighted average, and non-carcinogenic risks were also assessed in order to determine the sensory impact, odor contribution, and health impacts of NH3 and VSCs. The results revealed that odor pollution existed in all of the test sites, particularly in the sludge pump room and pre-dehydration workshop. NH3, H2S, and methyl mercaptan caused very strong odors, and levels of NH3 and H2S were enough to impact the health of on-site employees.