Coronin 2B deficiency induces nucleolar stress and neuronal apoptosis.

In eukaryotes, the nucleolus is the critical non-membranous organelle within nuclei that is responsible for ribosomal DNA (rDNA) transcription and ribosome biogenesis. The transcription of rDNA, a rate-limiting step for ribosome biogenesis, is tightly regulated to meet the demand for global protein synthesis in response to cell physiology, especially in neurons, which undergo rapid changes in morphology and protein composition during development and synaptic plasticity. However, it is unknown how the pre-initiation complex for rDNA transcription is efficiently assembled within the nucleolus in neurons. Here, we report that the nucleolar protein, coronin 2B, regulates rDNA transcription and maintains nucleolar function through direct interaction with upstream binding factor (UBF), an activator of RNA polymerase I transcriptional machinery. We show that coronin 2B knockdown impairs the formation of the transcription initiation complex, inhibits rDNA transcription, destroys nucleolar integrity, and ultimately induces nucleolar stress. In turn, coronin 2B-mediated nucleolar stress leads to p53 stabilization and activation, eventually resulting in neuronal apoptosis. Thus, we identified that coronin 2B coordinates with UBF to regulate rDNA transcription and maintain proper nucleolar function in neurons.

Unraveling the Prefrontal Cortex-Basolateral Amygdala Pathway's Role on Schizophrenia's Cognitive Impairments: A Multimodal Study in Patients and Mouse Models.

BACKGROUND AND HYPOTHESIS: This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. STUDY DESIGN: This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. STUDY RESULTS: Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. CONCLUSIONS: Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method.

Potential of novel iron 1,3,5-benzene tricarboxylate loaded on biochar to reduce ammonia and nitrous oxide emissions and its associated biological mechanism during composting.

In this study, a novel iron 1,3,5-benzene tricarboxylate loaded on biochar (BC-FeBTC) was developed and applied to kitchen waste composting. The results demonstrated that the emissions of NH3 and N2O were significantly reduced by 57.2% and 37.8%, respectively, compared with those in control group (CK). Microbiological analysis indicated that BC-FeBTC addition altered the diversity and abundance of community structure as well as key functional genes. The nitrification genes of ammonia-oxidizing bacteria were enhanced, thereby promoting nitrification and reducing the emission of NH3. The typical denitrifying bacterium, Pseudomonas, and critical functional genes (nirS, nirK, and nosZ) were significantly inhibited, contributing to reduced N2O emissions. Network analysis further revealed the important influence of BC-FeBTC in nitrogen transformation driven by functional microbes. These findings offer crucial scientific foundation and guidance for the application of novel materials aimed at mitigating nitrogen loss and environmental pollution during composting.

Serum proteome profiling reveals heparanase as a candidate biomarker for chronic thromboembolic pulmonary hypertension.

Determining novel biomarkers for early identification of chronic thromboembolic pulmonary hypertension (CTEPH) could improve patient outcomes. We used the isobaric tag for relative and absolute quantitation approach to compare the serum protein profiles between CTEPH patients and the controls. Bioinformatics analyses and ELISA were also performed. We identified three proteins including heparanase (HPSE), gelsolin (GSN), and secreted protein acidic and rich in cysteine (SPARC) had significant changes in CTEPH. The receiver operating characteristic curve analysis showed that the areas under the curve of HPSE in CTEPH diagnosis were 0.988. Furthermore, HPSE was correlated with multiple parameters of right ventricular function. HPSE concentrations were significantly higher in patients with a low TAPSE/sPAP ratio (≤0.31 mm/mmHg) (65.4 [60.5,68.0] vs. 59.9 [35.9,63.2] ng/mL, p < 0.05). The CTEPH patients treated by balloon pulmonary angioplasty had significantly lower HPSE levels. The study demonstrates that HPSE may be a promising biomarker for noninvasive detection of CTEPH.

Responses of greenhouse gas emissions to aeration coupled with functional membrane during industrial-scale composting of dairy manure: Insights into bacterial community composition and function.

Greenhouse gas (GHG) emissions from manure management processes deserve more attention. Using three industrial-scale experiments, this study comprehensively evaluated the effects of different aeration coupled with semi-permeable membrane-covered strategies on the structure and function of bacterial communities and their impact on GHG emissions during dairy manure aerobic composting. The succession of the bacterial communities tended to be consistent for similar aeration strategies. Ruminiclostridium and norank_f__MBA03 were significantly positively correlated with the methane emission rate, and forced aeration coupled with semi-permeable membrane-covered decreased GHG emissions by inhibiting these taxa. Metabolism was the most active function of the bacterial communities, and its relative abundance accounted for 75.69%-80.23%. The combined process also enhanced carbohydrate metabolism and amino acid metabolism. Therefore, forced aeration coupled with semi-permeable membrane-covered represented a novel strategy for reducing global warming potential by regulating the structure and function of the bacterial communities during aerobic composting of dairy manure.

Lactate promotes Salmonella intracellular replication and systemic infection via driving macrophage M2 polarization.

IMPORTANCE: The important enteropathogen Salmonella can cause lethal systemic infection via survival and replication in host macrophages. Lactate represents an abundant intracellular metabolite during bacterial infection, which can also induce macrophage M2 polarization. In this study, we found that macrophage-derived lactate promotes the intracellular replication and systemic infection of Salmonella. During Salmonella infection, lactate via the Salmonella type III secretion system effector SteE promotes macrophage M2 polarization, and the induction of macrophage M2 polarization by lactate is responsible for lactate-mediated Salmonella growth promotion. This study highlights the complex interactions between Salmonella and macrophages and provides an additional perspective on host-pathogen crosstalk at the metabolic interface.

[Alda-1 alleviates brain injury after cardiopulmonary resuscitation by regulating acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 pathway-mediated ferroptosis in swine].

OBJECTIVE: To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine. METHODS: Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 ß protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting. RESULTS: Compared with the Sham group, the serum levels of NSE and S100ß after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 ß starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (µg/L): 24.1±2.4 vs. 28.2±2.1, S100 ß (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (µmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway. CONCLUSIONS: Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.

Increasing systemic chronic inflammation mediated the association between poor sleep during pregnancy and gestational cardiovascular health.

OBJECTIVES: This study aimed to examine the association between sleep behaviors and cardiovascular health (CVH) during pregnancy and test whether high-sensitivity C-reactive protein (hs-CRP) mediates this association. METHODS: The study included 4204 pregnant women from the Maternal and Infant Health cohort study in Hefei (MIH-Hefei). Information on sleep (chronotype, sleep duration, snoring, daytime sleepiness, and insomnia) was collected through a touch-screen structured questionnaire at 16-23 weeks' gestation. CVH (body mass index, blood pressure, total cholesterol, glucose, and smoking) and hs-CRP were measured at 24-28 weeks' gestation. The role of hs-CRP in the association between sleep and CVH was explored in a mediation analysis, while adjusting for multiple confounding factors. RESULTS: Poor sleep score was significantly associated with poor gestational CVH metrics, including an RR of 0.872 (95% CI, 0.810, 0.938) for having all ideal (vs. any nonideal) CVH metrics; hs-CRP level was significantly associated with poor gestational CVH metrics, including an RR of 0.531 (95% CI, 0.432, 0.609) for having all ideal (vs. any nonideal) CVH metrics. Sleep scores were positively correlated with hs-CRP level (ß, 0.020, 95% CI, 0.006, 0.034). Mediation analysis revealed that the association between sleep and CVH mediated by hs-CRP was 12.31% (indirect effect, -0.0095, 95% CI, -0.0167, -0.0042). CONCLUSIONS: Poor sleep during pregnancy, particularly late chronotype and snoring, may worsen CVH by increasing systemic chronic inflammation.

Imaging the metabolic reprograming of fatty acid synthesis pathway enables new diagnostic and therapeutic opportunity for breast cancer.

BACKGROUND: Reprogrammed metabolic network is a key hallmark of cancer. Profiling cancer metabolic alterations with spatial signatures not only provides clues for understanding cancer biochemical heterogeneity, but also helps to decipher the possible roles of metabolic reprogramming in cancer development. METHODS: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technique was used to characterize the expressions of fatty acids in breast cancer tissues. Specific immunofluorescence staining was further carried out to investigate the expressions of fatty acid synthesis-related enzymes. RESULTS: The distributions of 23 fatty acids in breast cancer tissues have been mapped, and the levels of most fatty acids in cancer tissues are significantly higher than those in adjacent normal tissues. Two metabolic enzymes, fatty acid synthase (FASN) and acetyl CoA carboxylase (ACC), which being involved in the de novo synthesis of fatty acid were found to be up-regulated in breast cancer. Targeting the up-regulation of FASN and ACC is an effective approach to limiting the growth, proliferation, and metastasis of breast cancer cells. CONCLUSIONS: These spatially resolved findings enhance our understanding of cancer metabolic reprogramming and give an insight into the exploration of metabolic vulnerabilities for better cancer treatment.

High oil content inhibits humification in food waste composting by affecting microbial community succession and organic matter degradation.

Composting is an effective technology to realize resource utilization of food waste in rural China. However, high oil content in food waste limits composting humification. This study investigated the effects of blended plant oil addition at different proportions (0, 10, 20, and 30%) on the humification of food waste composting. Oil addition at 10%-20% enhanced lignocellulose degradation by 16.6%-20.8% and promoted humus formation. In contrast, the high proportion of oil (30%) decreased the pH, increased the electrical conductivity, and reduced the seed germination index to 64.9%. High-throughput sequencing showed that high oil inhibited the growth and reproduction of bacteria (Bacillus, Fodinicurvataceae, and Methylococcaceae) and fungi (Aspergillus), attenuated their interaction, thus, reducing the conversion of organic matter, such as lignocellulose, fat, and total sugar, to humus, consequently leading to negative impacts on composting humification. The results can guide composting parameter optimization and improve effective management of rural food waste.

EFFECTS OF MESENCHYMAL STEM CELLS ON POSTRESUSCITATION RENAL AND INTESTINAL INJURIES IN A PORCINE CARDIAC ARREST MODEL.

ABSTRACT: Objectives: Systemic ischemia-reperfusion triggered by cardiac arrest (CA) and resuscitation often causes postresuscitation multiple organ injuries. Mesenchymal stem cells (MSCs) have been proven to be a promising treatment for regional renal and intestinal ischemia reperfusion injuries. This study aimed to investigate the effects of MSCs on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in a porcine CA model. Methods: Twenty-two male pigs were randomly assigned to the sham (n = 6), CA/CPR (n = 8), and CA/CPR + MSC (n = 8) groups. Mesenchymal stem cells were differentiated from human embryonic stem cells and then intravenously administered at a dose of 2.5 × 10 6 /kg at 1.5 and 3 d before the CA/CPR procedure. The experimental model was established by 8 min of untreated CA, followed by 8 min of CPR. Renal and intestinal injuries were evaluated based on the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid-binding protein, and diamine oxidase at 1, 2, 4, and 24 h after resuscitation. At the end of the experiment, pathological damage was determined by cell apoptosis and ferroptosis in the renal and intestinal tissues. Results: During CPR, five pigs in the CA/CPR group and seven pigs in the CA/CPR + MSC group were successfully resuscitated. After resuscitation, the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid-binding protein, and diamine oxidase were significantly increased in the CA/CPR and CA/CPR + MSC groups compared with those in the sham group. However, MSC administration significantly decreased the levels of renal and intestinal injury biomarkers compared with those in the CA/CPR group. Cell apoptosis and ferroptosis, which were indicated by the levels of apoptotic cells, iron deposition, lipid peroxidation, antioxidants, and ferroptosis-related proteins, were observed in renal and intestinal tissues after resuscitation in the CA/CPR and CA/CPR + MSC groups. Nevertheless, both were significantly milder in the CA/CPR + MSC group than in the CA/CPR group. Conclusions: MSC administration was effective in alleviating postresuscitation renal and intestinal injuries possibly through inhibition of cell apoptosis and ferroptosis in a porcine CA model.

HBV X Protein Induces Degradation of UBXN7, a Novel Negative Regulator of NF-κB Signaling, to Promote HBV Replication.

Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma. However, the function and mechanism of the effect of HBV on host protein ubiquitination remain largely unknown. We aimed at characterizing whether and how HBV promotes self-replication by affecting host protein ubiquitination. In this study, we identified UBXN7, a novel inhibitor for nuclear factor kappa B (NF-κB) signaling, was degraded via interaction with HBV X protein (HBx) to activate NF-κB signaling and autophagy, thereby affecting HBV replication. The expression of UBXN7 was analyzed by Western blot and quantitative reverse transcription polymerase chain reaction in HBV-transfected hepatoma cells and HBV-infected primary human hepatocytes (PHHs). The effects of UBXN7 on HBV replication were analyzed by using in vitro and in vivo assays, including stable isotope labeling by amino acids in cell culture (SILAC) analysis. Changes in HBV replication and the associated molecular mechanisms were analyzed in hepatoma cell lines. SILAC analyses showed that the ubiquitination of UBXN7 was significantly increased in HepG2.2.15 cells compared with control cells. After HBV infection, HBx protein interacted with UBXN7 to promote K48-linked ubiquitination of UBXN7 at K99, leading to UBXN7 degradation. On the other hand, UBXN7 interacted with the ULK domain of IκB kinase ß through its ubiquitin-associating domain to facilitate its degradation. This in turn reduced NF-κB signaling, leading to reduced autophagy and consequently decreased HBV replication.

Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue.

Ischemic stroke is the most common type of cerebrovascular disease with high mortality and poor prognosis, and cerebral ischemia-reperfusion (CI/R) injury is the main murderer. Here, we attempted to explore the effects and mechanism of Xuesaitong (XST) combined with dexmedetomidine (Dex) on CI/R injury in rats. First, a rat model of CI/R injury was constructed via the middle cerebral artery occlusion (MCAO) method and treated with XST and Dex alone or in combination. Then, on the 5th and 10th days of treatment, the neurological impairment was assessed using the modified neurological severity scores (mNSS), the 8-arm radial maze test (8ARMT), novel object recognition test (NORT), and fear conditioning test (FCT). H&E staining was performed to observe the pathological changes of the hippocampus. ELISA and related kits were used to assess the monoamine neurotransmitters and antioxidant enzyme activities in the hippocampus. The ATP, mitochondrial membrane potential levels, and qRT-PCR of genes related to mitochondrial function were determined to assess mitochondrial functions in the hippocampus and western blot to determine Keap1/Nrf2 signaling pathway and mitophagy-related protein expression. The results showed that XST combined with Dex significantly reduced mNSS, improved spatial memory and learning deficits, and enhanced fear memory and cognitive memory ability in CI/R rats, which was superior to single-drug treatment. Moreover, XST combined with Dex treatment improved hippocampal histopathological damage; significantly increased the levels of monoamine neurotransmitters, neurotrophic factors, ATP, and mitochondrial membrane potential; and upregulated the activities of antioxidant enzymes and the expression of mitophagy-related proteins in the hippocampus of CI/R rats. XST combined with Dex treatment also activated the Keap1/Nrf2 signaling and upregulated the protein expression of downstream antioxidant enzymes HO-1 and NQ. Altogether, this study showed that a combination of XST and Dex could activate the Keap1/Nrf2 signaling and mitophagy to protect rats from CI/R-related neurological impairment.

Clinical features and metabolic reprogramming of atherosclerotic lesions in patients with chronic thromboembolic pulmonary hypertension.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) patients may present with atherosclerotic lesions in their pulmonary arteries, but their clinical characteristics remain unclear. The metabolic pathways associated with the atherosclerotic lesions may explain their occurrence and have implications for interventions, but they have not been investigated. Methods: We collected pulmonary endarterectomy (PEA) samples of CTEPH patients from December 2016 to August 2021. Following a detailed pathological examination of the PEA specimen, the patients were divided into those with and without lesions, and age- and sex matching were performed subsequently using propensity score matching (n = 25 each). Metabolomic profiling was used to investigate the metabolites of the proximal lesions in the PEA specimens. Results: In our study population, 27.2% of all PEA specimens were found to contain atherosclerotic lesions. CTEPH patients with atherosclerotic lesions were more likely to have a history of symptomatic embolism and had a longer timespan between embolism and surgery, whereas the classic risk factors of systemic and coronary circulation could not distinguish CTEPH patients with or without atherosclerotic lesions. Metabolomic profiling revealed that the formation of atherosclerotic lesions in CTEPH was closely related to altered glycine, serine, and threonine metabolic axes, possibly involved in cellular senescence, energy metabolism, and a proinflammatory microenvironment. Conclusion: The occurrence of atherosclerotic lesions in the pulmonary arteries of CTEPH was associated with symptomatic thromboembolic history and prolonged disease duration. The results revealed a new link between atherosclerotic lesions and aberrant amino acid metabolism in the context of CTEPH for the first time. This study has characterized the clinical and metabolic profiles of this distinct group of CTEPH patients, providing new insights into disease pathogenesis and potential interventions.

Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer.

Previous studies have shown that some anesthesia drugs can inhibit tumor growth and metastasis. As a clinical anesthetic drug, dezocine has been reported to play an important role in immune function. However, the effects of dezocine on ovarian cancer cell growth and metastasis are not fully understood. In this study, we found that dezocine dose-dependently inhibited the viability of ES-2 and SKOV3 cells. Dezocine suppressed the migration and invasion abilities of ovarian cancer cells, and promoted apoptosis. Moreover, the Akt/mTOR signaling pathway was also inhibited by dezocine. Furthermore, mechanism study showed that dezocine could significantly inhibit the expression of CRABP2, and CRABP2 overexpression reversed the inhibitory effects of dezocine on ovarian cancer cell proliferation and migration. In conclusion, dezocine has significant anti-tumor effects on the growth and metastatic potential of ovarian cancer cells, and CRABP2 functions as a downstream effector of dezocine.

Edible oleogels stabilized solely by stigmasterol: effect of oil type and gelator concentration.

BACKGROUND: Phytosterols are considered to be one of the most promising gelators for obtaining oleogel because of their additional health benefits and natural coexist with vegetable oils. Previous studies have confirmed that individual phytosterols are not capable of structuring vegetable oils unless they act synergistically with other components. However, based on the self-assembly properties of stigmasterol (ST) in organic solvents, we speculate that it can also structure vegetable oils as a gelator alone. RESULTS: For the first time, the present study confirmed the feasibility of using ST alone as a gelator for structuring of vegetable oils, including rapeseed oil (RSO), olive oil (OLO) and flaxseed oil (FSO). RSO had the lowest ST gelation concentration (4%, w/w), and the oil-binding capacity and firmness value of the oleogels were the highest. The rheological results showed that all the samples were gelatinous (G' > G″). The results of differential scanning calorimeter and X-ray diffraction further confirmed that the properties of RSO-based oleogels are superior to those prepared by OLO and FSO. The microscopic results also confirmed that the crystal structure of RSO oleogels was more uniform, smaller and more densely distributed. CONCLUSION: The structural properties of the oleogels were positively correlated with the ST concentration, and various analysis indicators showed that the performance of the oleogel based on RSO was better than that of OLO and FSO. In summary, the present study used ST as a gelator to successfully prepare oleogels with excellent properties, which provides a feasible reference for researchers in related fields. © 2022 Society of Chemical Industry.

Effects of the functional membrane covering on the gas emissions and bacterial community during aerobic composting.

The effects of the functional membrane covering on the gas emissions and bacterial community during dairy cow manure aerobic composting were investigated. A lab-scale aerobic composting experiment was conducted with the control group (CK), Gore group (Gore), and ZT group (ZT), namely, without and with two functional membranes. Covering the functional membrane retained heat and improved the seed germination index in Gore and ZT groups. Compared with the CK group, the Gore membrane decreased NH3 and N2O emissions by 11.77% and 26.40%, respectively. The ZT membrane decreased N2O and CO2 emissions by 68.44% and 1.56%, respectively. The Gore and ZT membranes decreased the global warming potential by 16.97% and 53.41%, respectively. Moreover, Covering the two functional membranes improved the Actinobacteria relative abundance and were conducive to the degradation of volatile solid. Altogether, membrane-covered aerobic composting is an important technology for the resource utilization of organic waste.

Effects of semi-permeable membrane covering coupled with intermittent aeration on gas emissions during aerobic composting from the solid fraction of dairy manure at industrial scale.

In this study, the effects of covering the compost pile with a semi-permeable membrane in combination with intermittent aeration on the gas emissions during aerobic composting from the solid fraction of dairy manure at industrial scale were investigated. A large-scale composting experiment was carried out to compare a membrane-covered (CT) group with a control (CK) group. The results indicated that the CT group could maintain a suitable aerobic and positive micro-pressure environment. The carbon dioxide, methane, nitrous oxide, and ammonia emissions outside the membrane during the aeration interval were reduced by 64.23%, 70.07%, 54.87%, and 11.32%, respectively, compared with that inside the membrane. It was also determined that the methane and nitrous oxide emissions from the CT group were reduced by 99.89% and 60.48% relative to the CK group, confirming that the combined process represented a novel strategy for reducing gas emissions during dairy manure composting.

Salmonella Typhimurium reprograms macrophage metabolism via T3SS effector SopE2 to promote intracellular replication and virulence.

Salmonella Typhimurium establishes systemic infection by replicating in host macrophages. Here we show that macrophages infected with S. Typhimurium exhibit upregulated glycolysis and decreased serine synthesis, leading to accumulation of glycolytic intermediates. The effects on serine synthesis are mediated by bacterial protein SopE2, a type III secretion system (T3SS) effector encoded in pathogenicity island SPI-1. The changes in host metabolism promote intracellular replication of S. Typhimurium via two mechanisms: decreased glucose levels lead to upregulated bacterial uptake of 2- and 3-phosphoglycerate and phosphoenolpyruvate (carbon sources), while increased pyruvate and lactate levels induce upregulation of another pathogenicity island, SPI-2, known to encode virulence factors. Pharmacological or genetic inhibition of host glycolysis, activation of host serine synthesis, or deletion of either the bacterial transport or signal sensor systems for those host glycolytic intermediates impairs S. Typhimurium replication or virulence.

Downregulation of a novel flagellar synthesis regulator AsiR promotes intracellular replication and systemic pathogenicity of Salmonella typhimurium.

The intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits host macrophage as a crucial survival and replicative niche. To minimize host immune response stimulated by flagellin, the expression of flagellar genes is downregulated during S. Typhimurium growth within host macrophages. However, the underlying mechanisms are largely unknown. In this study, we show that STM14_1285 (named AsiR), a putative RpiR-family transcriptional regulator, which is downregulated within macrophages as previously reported and also confirmed here, positively regulates the expression of flagellar genes by directly binding to the promoter of flhDC. By generating an asiR mutant strain and a strain that persistently expresses asiR gene within macrophages, we confirmed that the downregulation of asiR contributes positively to S. Typhimurium replication in macrophages and systemic infection in mice, which could be attributed to decreased flagellar gene expression and therefore reduced flagellin-stimulated secretion of pro-inflammatory cytokines IL-1ß and TNF-α. Furthermore, the acidic pH in macrophages is identified as a signal for the downregulation of asiR and therefore flagellar genes. Collectively, our results reveal a novel acidic pH signal-mediated regulatory pathway that is utilized by S. Typhimurium to promote intracellular replication and systemic pathogenesis by repressing flagellar gene expression.