Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. ...Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.
Emerging evidence indicates that M2-polarized tumor-associated macrophages (TAMs) directly participate in tumor initiation, progression and metastasis. However, to date, few studies have investigated ...novel strategies for inhibiting TAMs in order to overcome osteosarcoma. In this study, we reported that M2 macrophages were enriched in osteosarcoma tissues from patients, and M2-polarized TAMs enhanced cancer initiation and stemness of osteosarcoma cells, thereby establishing M2-polarized TAMs as a therapeutic target for blocking osteosarcoma formation. We also found that all-trans retinoic acid (ATRA) weakened TAM-induced osteosarcoma tumor formation by inhibiting M2 polarization of TAMs in vivo, and inhibited the colony formation, as well as sphere-formation capacity of osteosarcoma cells promoted by M2-type macrophages in vitro. Furthermore, M2-type macrophages enhanced cancer stem cells (CSCs) properties as assessed by increasing the numbers of CD117
Stro-1
cells accompanied by the upregulation of CSC markers (CD133, CXCR4, Nanog, and Oct4), which could clearly be reduced by ATRA. Taken together, the results of this study demonstrated the role of M2-polarized TAMs in osteosarcoma initiation and stemness by activating CSCs, and indicated that ATRA treatment is a promising approach for treating osteosarcoma by preventing M2 polarization of TAMs.
Background
The link between body mass index (BMI) and disease characteristics in rheumatoid arthritis (RA) remains controversial. Body composition (BC) has been more frequently recommended to be used ...instead of BMI for more accurate assessment. Our study aimed to investigate the characteristics of BC in RA patients and their associations with disease characteristics.
Methods
Body composition was assessed in consecutive Chinese RA patients and control subjects by bioelectric impedance analysis. Overfat was defined by body fat percentage (BF%) as ≥25% for men and ≥35% for women. Myopenia was defined by appendicular skeletal muscle mass index (ASMI) ≤7.0 kg/m2 in men and ≤5.7 kg/m2 in women. BMI and clinical data including disease activity, function, and radiographic assessment were collected. Active disease was defined by disease activity score in 28 joints with four variables including C‐reactive protein (DAS28‐CRP) ≥2.6. Functional limitation was defined as Stanford health assessment questionnaire disability index (HAQ‐DI) >1. Radiographic joint damage (RJD) was defined as the Sharp/van der Heijde modified sharp score (mTSS) >10.
Results
There were 457 RA patients (mean age 49.5 ± 13.1 years old with 82.7% women) and 1860 control subjects (mean age 34.3 ± 9.9 years old with 51.2% women) recruited. Comparisons of BMI and BC between RA patients and control subjects in age and gender stratification showed that lower BMI with 17.7% underweight and lower ASMI with 45.1% myopenia are the main characteristics in RA patients. Compared with those without myopenia, RA patients with myopenia had significantly higher DAS28‐CRP (median 3.5 vs. 3.0), higher HAQ‐DI (median 0.38 vs. 0.13) with higher rate of functional limitation (24.8% vs. 7.6%), and higher mTSS (median 22.3 vs. 9.0) with more RJD (71.8% vs. 45.8%) (all P < 0.001). Multivariate logistic regression analysis showed myopenia were positively associated with functional limitation (OR = 2.546, 95% CI: 1.043–6.217) and RJD (OR = 2.660, 95% CI: 1.443–4.904). All RA patients were divided into four BC subgroups according to overfat and myopenia. Those with both overfat and myopenia had the worst disease characteristics. After adjustment for confounding factors, significant additive interactions were observed between overfat and myopenia in active disease (AP = 0.528, 95% CI: 0.086–0.971), functional limitation (AP = 0.647, 95% CI: 0.356–0.937), and RJD (AP = 0.514, 95% CI: 0.139–0.890).
Conclusions
Myopenia is very common in RA patients that is associated with functional limitation and joint damage in RA. Further research on the underlying mechanism and the effect of skeletal muscle mass improvement in RA management are worth exploring in the future.
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•Molecular mechanisms of hepatic insulin resistance in nonalcoholic fatty liver disease.•Lipid metabolism and inflammation are the key basic mechanisms of all mechanisms.•For the ...treatment of NAFLD, improving lipid metabolism and inflammatory drugs is a potential direction.
The prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population is estimated at 25 %, and there is currently no effective treatment of NAFLD. Although insulin resistance (IR) is not the only factor causing the pathogenesis of NAFLD, hepatic IR has a cause-effective relationship with NAFLD. Improving hepatic IR is a potential therapeutic strategy to treat NAFLD. This review highlights the molecular mechanisms of hepatic IR in the development of NAFLD. Available data on potential drugs including glucagon-like peptide 1 receptor (GLP-1) agonists, peroxisome proliferator-activated receptor (PPAR-γ/α/δ) agonists, farnesoid X receptor (FXR) agonists, etc. are carefully discussed.
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•Gegen Qinlian Decoction abated nonalcoholic steatohepatitis associated liver injuries.•Gegen Qinlian Decoction could improve lipid metabolism.•Gegen Qinlian Decoction had ...anti-oxidative stress effect.•Gegen Qinlian Decoction had anti-inflammatory effect.•Anti-inflammatory effect involved inhibition of TLR4 signaling pathways.
Gegen Qilian Decoction (GGQLD) is a well-established classic Chinese medicine prescription in treating nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of GGQLD action on NASH is still not clear. This study aimed to assess the anti-NASH effect of GGQLD, and to explore its molecular mechanisms in vivo and in vitro. In HFD-fed rats, GGQLD decreased significantly serum triglyceride (TG), cholesterol (CHO), total bile acid (TBA), low-density lipoprotein (LDL), free fatty acid (FFA) and lipopolysaccharide (LPS) levels, increased levels of differentially expressed proteins (DEPs) Ahcy, Gpx1, Mat1a, GNMT, and reduced the expression of ALDOB. In RAW264.7 macrophages, GGQLD reduced the expression levels of inflammatory factors TNF-α and IL-6 mRNA, and diminished NASH by increasing differentially expressed genes (DEGs) CBS, Mat1a, Hnf4α and Pparα to reduce oxidative stress or lipid metabolism. The results of DEGs verification also showed that GGQLD up-regulated expressions of Hnf4α, Pparα and Cbs genes. In HepG2 cells, GGQLD decreased IL-6 levels and intracellular TG content, and inhibited FFA-induced expression of toll-like receptor 4 (TLR4). In summary, GGQLD abates NASH associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of TLR4 signal pathways. These findings provide new insights into the anti-NASH therapy by GGQLD.
Increasing number of resistant bacteria have emerged with the overuse of antibiotics, which indicates that the bacterial infection has become a global challenge. Furthermore, the pollution of ...antibiotics to the environment has become a serious threat to public health. It is known that toxins produced by bacteria are the main cause of bacterial infections. Photothermal therapy is an effective antibacterial approach. However, the photothermal reagents cannot eliminate bacterial toxins, and even some anti-bacterial materials are toxic. Here, we synthesized a biomimetic recycled nanoparticle, red blood cell (RBC) membrane-coated Fe3O4 nanoparticles (RBC@Fe3O4), as an antibacterial agent. The RBC@Fe3O4 nanoparticles act as nano-sponges to trap toxins and then kill them all with a photothermal effect. We can describe this process simply as a battle between two armies. Our strategy is to disarm the "enemy" so that we can easily kill the "enemy" who has no power, which results in enhancing the bactericidal efficacy. The toxin of methicillin-resistant Staphylococcus aureus (MRSA) was absorbed by RBC@Fe3O4in vitro. In addition, in vivo studies proved that the RBC@Fe3O4 nanoparticles confer obvious survival benefits against toxin-induced lethality by absorbing the toxin of MRSA. Furthermore, using a mouse model of MRSA wound infection, the RBC@Fe3O4 nanoparticles with laser irradiation were found to have a superior wound-healing effect. Simultaneously, the RBC@Fe3O4 nanoparticles could be recycled in a simple way without affecting the bactericidal efficacy. The highly biocompatible and recyclable RBC@Fe3O4 biomimetic nanoparticles based on photothermal therapy and bacterial toxin adsorption strategy are promising for treating bacterial infections.
The efficiently renewable bioethanol can help to alleviate energy crisis and environmental pollution. Genetically modified strains for efficient use of xylose and developing lignocellulosic ...hydrolysates play an essential role in facilitating cellulosic ethanol production. Here we present a promising strain GRE3
via
overexpressed in a previously reported
strain WXY70. A comprehensive evaluation of the fermentation level of GRE3
in alkaline-distilled sweet sorghum bagasse, sorghum straw and xylose mother liquor hydrolysate. Under simulated corn stover hydrolysate, GRE3
produced 53.39 g/L ethanol within 48 h. GRE3
produced about 0.498 g/g total sugar in sorghum straw hydrolysate solution. Moreover, GRE3
consumed more xylose than WXY70 in the high-concentration xylose mother liquor. Taken together, GRE3
could be a candidate strain for industrial ethanol development, which is due to its remarkable fermentation efficiency during different lignocellulosic hydrolysates.
Microbiota from herbivore rumen is of great interest for mining glycoside hydrolases for lignocellulosic biomass biorefinement. We previously isolated a highly active but poorly thermostable xylanase ...(LXY) from a rumen fluid fosmid library of Hu sheep, a local high-reproductive species in China. In this study, we used a universal enzyme-engineering strategy called SpyTag/SpyCatcher molecular cyclization to improve LXY stability via isopeptide-bond-mediated ligation. Both linear and cyclized LXY (L- and C-LXY, respectively) shared similar patterns of optimal pH and temperature, pH stability, and kinetic constants (
k
m
and
V
max
). However, the C-LXY showed enhanced thermostability, ion stability, and resilience to aggregation and freeze–thaw treatment than L-LXY, without compromise of its catalytic efficiency. Circular dichroism and intrinsic and 8-anilino-1-naphthalenesulfonic acid-binding fluorescence analysis indicated that the cyclized enzyme was more capable of maintaining its secondary and tertiary structures than the linear enzyme. Taken together, these results promote the cyclized enzyme for potential applications in the feed, food, paper pulp, and bioenergy industries.
Reaction rates, product distributions, and catalyst deactivation are reported for SAPO-34, MgO, MoO3, and physical blends of these materials in fixed-bed reactors. Methanol is converted to small ...olefins (C2 and C3 primarily) over SAPO-34. A small fraction of the methanol oligomerizes further, forming coke that deactivates the catalyst. Methanol is dehydrogenated to CO and H2 over MgO catalysts. Methanol is oxidized to CO2 over MoO3 catalysts. Physically blending SAPO-34 with MgO or MoO3 reduces the reaction selectivity for the methanol to olefins (MTO) reaction. Physical mixing of SAPO-34 and MgO favorably extends the catalyst lifetimes by reducing the rate of coke formation on SAPO-34. This is explained by opening up parallel reaction pathways involving oxygenated reaction intermediates. In contrast, SAPO-34 deactivation is more rapid when SAPO-34 is physically blended with MoO3. MgO by itself shows almost no catalytic activity for methanol. However, when MgO is sandwiched between layers of SAPO-34, the catalytic activity and production distribution from methanol is significantly altered to favor carbon oxides in comparison to SAPO-34 by itself. MgO is only catalytically active when it is sandwiched between layers of SAPO-34, demonstrating that reaction intermediates are transported from SAPO-34 to MgO and back again. Blends of MoO3 and SAPO-34 showed that catalyst deactivation was more rapid in comparison to SAPO-34 alone; methanol was oxidized to formaldehyde over MoO3, which was transported to SAPO-34, where the acidic SAPO-34 catalyst is assumed to polymerize the formaldehyde. The data indicate that acid-catalyzed reactions critical to MTO, oligomerization, and scission reactions occur on SAPO-34. MgO-catalyzed methanol dehydrogenation and MoO3-catalyzed methanol oxidation. Physical blends of catalysts can open up new reaction pathways through coupling of different catalyst functionalities that may provide a simple and convenient method for tuning catalytic performance.
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