•Cellular protein hnRNPAB interacts with avian influenza viral protein PB2.•hnRNPAB binds with PB2 mRNA.•hnRNPAB inhibits PB2 mRNA nuclear export and PB2 protein expression level.•hnRNPAB restricts ...the polymerase activity and replication of AIV.•AIV infection promotes the nuclear accumulation of hnRNPAB in DF-1 cells.
The PB2 protein of avian influenza virus (AIV) is essential for transcription and replication of virus genome. In this study, we reported that chicken heterogenous nuclear riboncleoprotein AB (hnRNPAB) cooperated with avian influenza viral protein PB2 and inhibited the polymerase activity and virus replication. We found that hnRNPAB was associated with PB2 mRNA and overexpression of hnRNPAB reduced PB2 mRNA nuclear export and PB2 protein level, but had no influence on PB2 mRNA level. At the same time, overexpression of hnRNPAB also reduced protein levels rather than mRNA levels of PA, PB1 and NP. In addition, overexpression of hnRNPAB restricted the polymerase activity and virus replication, while knockdown of hnRNPAB resulted in enhanced polymerase activity and virus replication. Lastly, virus infection induced the nuclear accumulation of hnRNPAB, but did not cause the change of expression level of endogenous hnRNPAB in DF-1 cells. Collectively, these findings suggested that hnRNPAB played a restrictive role in polymerase activity and virus replication potentially through inhibiting PB2 mRNA nuclear export and PB2 protein level.
In the JCOG0501 study, neoadjuvant chemotherapy (NAC) failed to demonstrate survival benefits for type 4 and large type 3 gastric cancer (GC). The prognosis of these patients is still poor. We ...conducted this study to explore the value of NAC with non-SP regimens for type 4 and large type 3 GC in the Chinese population.
We retrospectively collected data from our electronic medical record system. Patients with large type 3 or type 4 GC who underwent D2 gastrectomy and AC were included. Patients were divided into two groups based on whether they received NAC: the CSC (NAC + surgery + AC) and SC (surgery + AC) groups. The survival and perioperative outcomes for large type 3 or type 4 GC were analyzed between the CSC and SC groups, separately.
Between May 2009 and December 2018, 189 patients were reviewed. Among large type 3 GC, the 5-year overall survival (OS) rates for patients in the CSC and SC groups were 54.4 % and 28.0 %, respectively (P = 0.0008). Among type 4 GC, the 5-year OS rates for patients in the CSC and SC groups were 15.8 % and 24.8 %, respectively (P > 0.05).
This study showed NAC can improve the prognosis of large type 3 GC. However, NAC did not demonstrate significant survival advantages for type 4 GC.
•Large type 3 GC in the CSC group had better survival than those in the SC group.•For large type 3 GC, neoadjuvant chemotherapy not only reduced surgical complications but also improved patient survival.•There was no statistically significant difference in survival analysis for type 4 GC between the CSC and SC groups.
Neuroinflammation has been identified as another significant pathogenic factor in Alzheimer's disease following Aβ amyloid deposition and tau protein hyperphosphorylation, activated in the central ...nervous system by glial cells in response to injury-related and pathogen-related molecular patterns. Moderate glial cell activity can be neuroprotective; however, excessive glial cell activation advances the pathology of Alzheimer's disease and is accompanied by structural changes in the brain interface, with peripheral immune cells entering the brain through the blood-brain barrier, creating a vicious circle. The immunomodulatory properties of mesenchymal stem cells (MSCs) are primarily conveyed through extracellular vesicles (EVs). MSC-EVs participate in chronic inflammatory and immune processes by transferring nucleic acids, proteins and lipids from the parent cell to the recipient cell, thus MSC-EVs retain their immunomodulatory capacity while avoiding the safety issues associated with living cell therapy, making them a promising focus for immunomodulatory therapy. In this review, we discuss the modulatory effects of MSC-EVs on Alzheimer's disease-associated immune cells and the mechanisms involved in their treatment of the condition. We have found a clinical trial of MSC-EVs in Alzheimer's disease treatment and outlined the challenges of this approach. Overall, MSC-EVs have the potential to provide a safe and effective treatment option for Alzheimer's disease by targeting neuroinflammation.
The efficient separation of Zr(IV) ions from strong acidic and radioactive solutions is a significant challenge, especially in the context of the aqueous reprocessing of nuclear fuels. The complexity ...of such solutions, which are often characterized by high acidity and the presence of radioactive elements, poses formidable challenges for separation processes. Herein, several mesoporous silicas (HMS, MCM-41, KIT-6, and SiO
-70 Å) with excellent acid and radiation resistance properties were employed as sorbents to remove Zr(IV) ions from simulated high-level liquid waste. The batch experiments were designed to investigate the influence of adsorption time, HNO
concentration, initial Zr(IV) concentration, adsorbent dosage, and temperature on the adsorption behavior of Zr(IV). The results indicate that the adsorption equilibrium time of mesoporous silica materials was approximately 8 h, and all the adsorption processes followed the pseudo-second-order kinetics equation. The isotherms of Zr(IV) adsorption by KIT-6 exhibited good agreement with the Langmuir model, while the Freundlich model could be utilized to fit the adsorption on HMS, MCM-41, and SiO
-70 Å. The adsorption capacity of MCM-41 for Zr(IV) in 3 mol/L HNO
was 54.91 mg/g, which is three times the adsorption capacity reported for commercial silica gel (17.91 mg/g). The thermodynamic parameters indicate that the adsorption processes for zirconium are endothermic reactions. Furthermore, the mesoporous silicas exhibited a pronounced selectivity in the adsorption of Zr(IV) within a simulated high-level liquid waste containing 10 co-existing cations (3 mol/L HNO
). This suggests that mesoporous silicas have great potential for Zr(IV) removal in actual radioactive liquids with high acidity during spent fuel reprocessing.
Soil moisture (SM) measurements from ground stations are often after quality control (QC) in the operational system, but the QC flags may not be reliable in some cases when precipitation events or ...manual watering happen. This study applies the triple collocation (TC) method to conduct a cross-evaluation of SM data from ERA5 reanalysis estimates, ESA-CCI estimates, and ~2000 ground stations across the China domain. The results show that all datasets can capture the spatial pattern of SM in China. TC-based correlation coefficient (CC) and root mean square error (RMSE) show that the station data have worse performance in western and central China. For most stations, TC-based CC is between 0.6~0.9, and TC-based RMSE is between 0.01~0.06 m3/m3. In addition, TC-based metrics show good agreement with the CC between precipitation and SM, indicating that these metrics can reflect the quality of station data. We further selected typical stations (e.g., CC ≤ 0.2, RMSE ≥ 0.06 m3/m3) to check the quality of the QC procedure. The comparison shows that TC-based metrics can better represent the actual quality for these stations compared to raw QC flags. This study indicates that TC has the potential to detect problematic stations and could be a supplement to traditional QC of station observations.
The goal of this study was to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3-5 cm).
We ...retrospectively collected 122 cases of small solitary HCC treated at our center from Jan 2011 to Dec 2015, with diameters in the range of 3-5 cm. According to the treatment program received at our center, the patients were divided into liver resection (72 patients) and RFA (50 patients) groups.
In comparison with the RFA group, the resection group had a longer operative time, greater intraoperative blood loss (P < 0.01), more hepatic inflow occlusion, and a longer postoperative hospital stay (P < 0.01). The 1-, 3-, and 5-year expected overall survival rates and tumor-free survival rates were comparable between the two groups. Cox regression analysis showed that neither resection nor RFA was a significant risk factor for overall or tumor-free survival in HCC.
For solitary HCC of 3-5 cm in diameter, RFA can achieve better in-hospital clinical results and similar long-term outcomes than resection and can be considered for wide application, especially for central-location cases.
Multiple upwelling systems develop in the Indian Ocean during the summer monsoon. The Sri Lanka dome (SLD), which occurs in the open ocean off the east coast of Sri Lanka from June to September, is ...distinct from those near the coast. The SLD is characterized by uplifted thermocline and increased chlorophyll concentration. Mechanisms of the upwelling and its biogeochemical response are not well understood. Here, we explored the dynamics of the chlorophyll and sea-to-air CO2 flux in the SLD using ocean color and altimetry remote sensing data, together with other reanalysis products. We found that the occurrence of high chlorophyll concentration and sea-to-air CO2 flux happens along the pathway of the southwest monsoon current (SMC). The annual cycle of chlorophyll in the SLD has a one-month lag relative to that in the southern coast of Sri Lanka. The positive wind stress curl that forms in the SLD during the summer does not fully explain the seasonal chlorophyll maximum. Transport of the SMC, eddy activity, and associated frontal processes also play an important role in regulating the variability in chlorophyll. In the SLD, upwelled subsurface water has excess dissolved inorganic carbon (DIC) relative to the conventional Redfield ratio between DIC and nutrients; thus, upwelling and sub-mesoscale processes determine this region to be a net carbon source to the atmosphere.
Little is known about the transition mechanisms that govern early lymphoid lineage progenitors from common lymphoid progenitors (CLPs). Pellino2 (PELI2) is a newly discovered E3 ubiquitin ligase, ...which plays important roles in inflammation and immune system. However, the physiological and molecular roles of PELI2 in the differentiation of immune cells are largely unknown. Here, by using a conditional knockout mouse model, we demonstrated that PELI2 is required for the early B-cell development and stressed hematopoiesis. PELI2 interacted with and stabilized PU.1 via K63- polyubiquitination to regulate IL-7R expression. The defects of B cell development induced by PELI2 deletion were restored by overexpression of PU.1. Similarly, PELI2 promoted TCF3 protein stability via K63- polyubiquitination to regulate IL-7R expression, which is required for the proliferation of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. These results underscore the significance of PELI2 in both normal B lymphopoiesis and malignant B-cell acute lymphoblastic leukemia via the regulation of IL-7R expression, providing a potential therapeutic approach for BCP-ALL.
Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most common chronic liver disorders in the world, and yet has no approved pharmacotherapy due to the etiology is complex. ...In the last ten years, increasing evidence have identified the environmental pollutants as risk factors for MAFLD. However, the underlying mechanism remains unclear. Our study found that bromoacetic acid (BAA, a typical kind of environmental toxin) increased triglycerides and total cholesterol levels as well as induced obvious hepatic steatosis and inflammation. The lipidomics showed that ferroptosis was implicated in the environmental toxin–linked MAFLD. Besides, the analysis of microbial metabolomics showed significant change of gut microbiome in BAA groups and the content of gut microbiota metabolite (glycochenodeoxycholate, GCDCA) increased sharply. In vitro study, we observed features of ferroptotic cells by transmission electron microscopy after BAA/GCDCA treatment. Besides, we demonstrated that BAA/GCDCA significantly increased iron contents, with upregulating transferrin receptor (TFR) and acyl-CoA synthetase long-chain family 4 (ACSL4) expression levels. By contrast, iron chelator or silencing TFR relieved BAA/GCDCA-induced lipid metabolism disorder and inflammation. What's more, the interaction between TFR and ACSL4 was also identified. Taken together, we found that, in response to environmental toxin, gut microbiota metabolite GCDCA activates TFR-ACSL4-mediated ferroptosis, which triggered subsequent lipid metabolism disorder and inflammation. Moreover, these findings firstly highlighted the functional relevance among ferroptosis, lipid metabolism and gut microbiota metabolite during environmental pollutant exposure, which shed light on the deep mechanism of environmental toxin-related MAFLD, providing potential targets for the prevention of MAFLD.
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•BAA could promote the development of MAFLD.•Ferroptosis was involved in environmental toxin–linked MAFLD.•BAA changed gut microbiome profile and led to the elevation of GCDCA.•Gut microbiota metabolite GCDCA was associated with the activation of ferroptosis.•TFR-ACSL4 was the key ferroptotic signaling pathway in response to BAA/GCDCA.
•VD sufficiency activates VDR/RXR heterodimer to recruit NCOA1 and transactivate SPP1 in osteoblast cells.•VD deficiency impairs the NCOA1-VDR/RXR-mediated overexpression of SPP1, causing Akt1 ...inactivation and FOXO3a accumulation.•FOXO3a upregulates the expression of BAX, BID, and BIM, and subsequently induces apoptosis.•VD supplementation reactivates the SPP1-dependent antiapoptotic signaling and improves the outcomes of CHOM.
Chronic hematogenous osteomyelitis (CHOM) is a common bone disease characterized by the development of sequestra after bacterial infection. Emerging evidence has shown that vitamin D (VD) deficiency raises the risk of osteomyelitis, but the underlying mechanisms remain obscure. Here, we establish a CHOM model in VD diet-deficient mice by intravenous inoculation of Staphylococcus aureus. Whole-genome microarray analyses using osteoblast cells isolated from sequestra reveal significant downregulation of SPP1 (secreted phosphoprotein 1). Molecular basis investigations show that VD sufficiency activates the VDR/RXR (VD receptor/retinoid X receptor) heterodimer to recruit NCOA1 (nuclear receptor coactivator 1) and transactivate SPP1 in healthy osteoblast cells. Secreted SPP1 binds to the cell surface molecule CD40 to activate serine/threonine-protein kinase Akt1, which then phosphorylates forkhead box O3a (FOXO3a), blocking FOXO3a-mediated transcription. By contrast, VD deficiency impairs the NCOA1-VDR/RXR-mediated overexpression of SPP1, leading to the inactivation of Akt1 and the accumulation of FOXO3a. FOXO3a then upregulates the expression of the apoptotic genes BAX (Bcl2-associated X-protein), BID (BH3 interacting death domain), and BIM (Bcl2-interacting mediator of cell death), to induce apoptosis. Administration of the NCOA1 inhibitor gossypol to the CHOM mice also promotes the occurrence of sequestra. VD supplementation can reactivate the SPP1-dependent antiapoptotic signaling and improve the outcomes of CHOM. Collectively, our data reveal that VD deficiency promotes bone destruction in CHOM by the removal of SPP1-dependent antiapoptotic signaling.
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