Preparation of Fresh-Keeping Paper Using Clove Essential Oil through Pickering Emulsion and Maintaining the Quality of Postharvest Cherry Tomatoes.

This study focused on developing a Pickering emulsion fresh-keeping paper that contained clove essential oil (CEO). Cherry tomatoes served as the test material for assessing the preservative efficacy of fresh-keeping paper. The results showed that Pickering emulsion had strong stability. Additionally, the fresh-keeping paper had a good antioxidant activity and sustained-release effect on CEO. In terms of the preservation effect, 0.75 wt% CEO Pickering emulsion paper reduced the decay incidence and weight loss of cherry tomatoes during 12-day storage. Fresh-keeping paper could also play a positive role in protecting the sensory index and color difference of tomatoes. It slowed the decline rate of soluble solid concentration (SSC) and titrable acid (TA). The vitamin C (Vc) and hardness of preserved tomatoes using fresh-keeping paper were maintained at a high level. The paper also inhibited the growth of microorganisms significantly. Therefore, 0.75 wt% CEO Pickering emulsion fresh-keeping paper displayed considerable potential for application in the preservation of postharvest fruits and vegetables. It is a novel fruit and vegetable preservation material worthy of development.

Characterization and Antioxidant and Antibacterial Activities of Carboxymethylated Tamarind Seed Polysaccharide Composite Films Incorporated with ε-Polylysine and Their Application in Fresh-Cut Green Bell Pepper Preservation.

Traditional petroleum-based food-packaging materials have poor permeability, limited active packaging properties, and difficulty in biodegradation, limiting their application. We developed a carboxymethylated tamarind seed polysaccharide composite film incorporated with ε-polylysine (CTPε) for better application in fresh-cut agricultural products. The CTPε films exhibit excellent water vapor barrier properties, but the mechanical properties are slightly reduced. Fourier transform infrared spectroscopy and X-ray diffraction spectra indicate the formation of hydrogen bonds between ε-PL and CTP, leading to their internal reorganization and dense network structure. With the increase of ε-PL concentration, composite films showed notable inhibition of postharvest pathogenic fungi and bacteria, a significant enhancement of 2,2'- azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activity, and gradual improvement of wettability performance. Cytotoxicity experiments confirmed the favorable biocompatibility when ε-PL was added at 0.3% (CTPε2). In fresh-cut bell pepper preservation experiments, the CTPε2 coating effectively delayed weight loss and malondialdehyde increase preserved the hardness, color, and nutrients of fresh-cut peppers and prolonged the shelf life of the fresh-cut peppers, as compared with the control group. Therefore, CTPε composite films are expected to be a valuable packaging material for extending the shelf life of freshly cut agricultural products.

CD11b + CD43 hi Ly6C lo splenocyte-derived macrophages exacerbate liver fibrosis via spleen-liver axis.

BACKGROUND AND AIMS: Monocyte-derived macrophages (MoMFs), a dominant population of hepatic macrophages under inflammation, play a crucial role in liver fibrosis progression. The spleen serves as an extra monocyte reservoir in inflammatory conditions; however, the precise mechanisms of involvement of the spleen in the pathogenesis of liver fibrosis remain unclear. APPROACH AND RESULTS: By splenectomy and splenocyte transfusion, it was observed that splenic CD11b + cells accumulated intrahepatically as Ly6C lo MoMFs to exacerbate CCl 4 -induced liver fibrosis. The splenocyte migration into the fibrotic liver was further directly visualized by spleen-specific photoconversion with KikGR mice and confirmed by CD45.1 + /CD45.2 + spleen transplantation. Spleen-derived CD11b + cells purified from fibrotic livers were then annotated by single-cell RNA sequencing, and a subtype of CD11b + CD43 hi Ly6C lo splenic monocytes (sM-1s) was identified, which was markedly expanded in both spleens and livers of mice with liver fibrosis. sM-1s exhibited mature feature with high expressions of F4/80, produced much ROS, and manifested preferential migration into livers. Once recruited, sM-1s underwent sequential transformation to sM-2s (highly expressed Mif , Msr1 , Clec4d , and Cstb ) and then to spleen-derived macrophages (sMφs) with macrophage features of higher expressions of CX 3 CR1, F4/80, MHC class II, and CD64 in the fibrotic hepatic milieu. Furthermore, sM-2s and sMφs were demonstrated capable of activating hepatic stellate cells and thus exacerbating liver fibrosis. CONCLUSIONS: CD11b + CD43 hi Ly6C lo splenic monocytes migrate into the liver and shift to macrophages, which account for the exacerbation of liver fibrosis. These findings reveal precise mechanisms of spleen-liver axis in hepatic pathogenesis and shed light on the potential of sM-1 as candidate target for controlling liver diseases.

Extrahepatic factors in hepatic immune regulation.

The liver is a site of complex immune activity. The hepatic immune system tolerates harmless immunogenic loads in homeostasis status, shelters liver function, while maintaining vigilance against possible infectious agents or tissue damage and providing immune surveillance at the same time. Activation of the hepatic immunity is initiated by a diverse repertoire of hepatic resident immune cells as well as non-hematopoietic cells, which can sense "danger signals" and trigger robust immune response. Factors that mediate the regulation of hepatic immunity are elicited not only in liver, but also in other organs, given the dual blood supply of the liver via both portal vein blood and arterial blood. Emerging evidence indicates that inter-organ crosstalk between the liver and other organs such as spleen, gut, lung, adipose tissue, and brain is involved in the pathogenesis of liver diseases. In this review, we present the features of hepatic immune regulation, with particular attention to the correlation with factors from extrahepatic organ. We describe the mechanisms by which other organs establish an immune association with the liver and then modulate the hepatic immune response. We discuss their roles and distinct mechanisms in liver homeostasis and pathological conditions from the cellular and molecular perspective, highlighting their potential for liver disease intervention. Moreover, we review the available animal models and methods for revealing the regulatory mechanisms of these extrahepatic factors. With the increasing understanding of the mechanisms by which extrahepatic factors regulate liver immunity, we believe that this will provide promising targets for liver disease therapy.

Integrated Proteomics and Metabolomics Analysis in Pregnant Rat Hippocampus After Circadian Rhythm Inversion.

To investigate the changes in proteins, metabolites, and related mechanisms in the hypothalamus of pregnant rats after circadian rhythm inversion during the whole pregnancy cycle. A total of 12 Wistar female rats aged 7 weeks were randomly divided into control (six rats) and experimental (six rats) groups at the beginning of pregnancy. The control group followed a 12-h light and dark cycle (6 a.m. to 6 p.m. light, 6 p.m. to 6 a.m. dark the next day), and the experimental group followed a completely inverted circadian rhythm (6 p.m. to 6 a.m. light the next day, 6 a.m. to 6 p.m. dark). Postpartum data were collected until 7-24 h after delivery, and hypothalamus samples were collected in two groups for quantitative proteomic and metabolism analyses. The differential proteins and metabolites of the two groups were screened by univariate combined with multivariate statistical analyses, and the differential proteins and metabolites enriched pathways were annotated with relevant databases to analyze the potential mechanisms after circadian rhythm inversion. A comparison of postpartum data showed that circadian rhythm inversion can affect the number of offspring and the average weight of offspring in pregnant rats. Compared with the control group, the expression of 20 proteins and 37 metabolites was significantly changed in the experimental group. The integrated analysis between proteins and metabolites found that RGD1562758 and lysophosphatidylcholine acyltransferase 1 (LPCAT1) proteins were closely associated with carbon metabolism (choline, NAD+, L-glutamine, theobromine, D-fructose, and pyruvate) and glycerophospholipid metabolism (choline, NAD+, L-glutamine, phosphatidylcholine, theobromine, D-fructose, pyruvate, and arachidonate). Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the differential metabolites enriched in adenosine triphosphate (ATP)-binding cassette (ABC) transporters. Our study suggested that circadian rhythm inversion in pregnant rats may affect the numbers, the average weight of offspring, and the expressions of proteins and metabolism in the hypothalamus, which may provide a comprehensive overview of the molecular profile of circadian rhythm inversion in pregnant groups.

SLC1A1-mediated cellular and mitochondrial influx of R-2-hydroxyglutarate in vascular endothelial cells promotes tumor angiogenesis in IDH1-mutant solid tumors.

Mutant isocitrate dehydrogenase 1 (mIDH1) drives tumorigenesis via producing oncometabolite R-2-hydroxyglutarate (R-2-HG) across various tumor types. However, mIDH1 inhibitors appear only effective in hematological tumors. The therapeutic benefit in solid tumors remains elusive, likely due to the complex tumor microenvironment. In this study, we discover that R-2-HG produced by IDH1-mutant tumor cells is preferentially imported into vascular endothelial cells and remodels mitochondrial respiration to promote tumor angiogenesis, conferring a therapeutic vulnerability in IDH1-mutant solid tumors. Mechanistically, SLC1A1, a Na+-dependent glutamate transporter that is preferentially expressed in endothelial cells, facilitates the influx of R-2-HG from the tumor microenvironment into the endothelial cells as well as the intracellular trafficking of R-2-HG from cytoplasm to mitochondria. R-2-HG hijacks SLC1A1 to promote mitochondrial Na+/Ca2+ exchange, which activates the mitochondrial respiratory chain and fuels vascular endothelial cell migration in tumor angiogenesis. SLC1A1 deficiency in mice abolishes mIDH1-promoted tumor angiogenesis as well as the therapeutic benefit of mIDH1 inhibitor in solid tumors. Moreover, we report that HH2301, a newly discovered mIDH1 inhibitor, shows promising efficacy in treating IDH1-mutant cholangiocarcinoma in preclinical models. Together, we identify a new role of SLC1A1 as a gatekeeper of R-2-HG-mediated crosstalk between IDH1-mutant tumor cells and vascular endothelial cells, and demonstrate the therapeutic potential of mIDH1 inhibitors in treating IDH1-mutant solid tumors via disrupting R-2-HG-promoted tumor angiogenesis.

Splenectomy provides protective effects against CLP-induced sepsis by reducing TRegs and PD-1/PD-L1 expression.

The role of the spleen in sepsis is still controversial. Therefore, we investigated the effect of the spleen on sepsis-induced immune dysfunction in C57BL/6 mice subjected to caecal ligation and puncture (CLP). Changes in different immune cells and apoptotic cells in the spleen and peripheral blood were observed 4, 24 and 48 h after CLP. Then, we determined that 48 h following CLP was the most significant period of immunosuppression. Next, we divided the mice into four groups: control, CLP, CLP + spx (splenectomy 48 h after CLP) and spx + CLP (splenectomy surgery two weeks before CLP). Compared with the CLP mice, the CLP + spx and spx + CLP mice had improved survival rates and organ injuries, increased expression of inflammatory factors, a decreased proportion of regulatory T cells (Tregs), and reduced expression of the genes involved in the programmed cell death 1 and its ligand 1 (PD1-PDL1) pathway in immune cells and T-cell immunoglobulin-mucin domain 3 (Tim 3) and Galectin9 in the liver and lungs after 72 h in late-phase sepsis. In addition, the expression of PD-1 was significantly reduced in T cells in spx + CLP mice, and the expression of PD-L1 in myeloid-derived suppressor cells (MDSCs) was reduced in the CLP + spx group, especially in macrophages. These findings suggested that splenectomy could protect septic mice from exhaustion of immune cells by reducing the proliferation of Treg cells and expression of the PD-1/PD-L1 axis in immune cells during the immunosuppressive stage of sepsis. Splenectomy could also reduce liver and lung injuries possibly via the Tim 3 and/or Galectin-9 axis. The spleen is an important regulator of the occurrence and development of sepsis, which provides a new perspective to improve the prognosis of sepsis by regulating the spleen.

[Effect of ginger-separated moxibustion on fatigue, sleep quality and depression in patients with chronic fatigue syndrome: a randomized controlled trial].

OBJECTIVE: To observe the effect of ginger-separated moxibustion on fatigue, sleep quality and depression in the patients with chronic fatigue syndrome. METHODS: A total of 62 patients with chronic fatigue syndrome were randomized into an observation group (31 cases, 3 cases dropped off) and a control group (31 cases, 2 cases dropped off). In the control group, the patients had normal diet and proper physical exercise. In the observation group, on the basis of the control group, the ginger-separated moxibustion was added at Zhongwan (CV 12), Shenque (CV 8) and Guanyuan (CV 4), 30 min each time, once every two days, 3 times weekly. Separately, before treatment and after 4 weeks of treatment, the MOS item short form health survey (SF-36), the Pittsburgh sleep quality index (PSQI) scale and the self-rating depression scale (SDS) were adopted to evaluate the degrees of fatigue, sleep quality and depression in the patients of the two groups. RESULTS: In the observation group, the score of each item of SF-36, the score of each item of PSQI and SDS score after treatment were all improved significantly as compared with those before treatment respectively (P<0.05, P<0.01). In the control group, the scores of overall health, vitality and mental health in SF-36 and the score of sleep time of PSQI after treatment were improved as compared with those before treatment respectively (P<0.05). After treatment, the score of each item of SF-36, the scores of sleep quality, sleep time, sleep efficiency and sleep disorders of PSQI, as well as SDS score in the observation group were all better than those in the control group respectively (P<0.01, P<0.05). The score of SF-36 was relevant to the scores of PSQI and SDS in the patients of chronic fatigue syndrome (r =0.331, P<0.05; r =-0.706, P<0.01). The improvement value of SF-36 score was closely related to the improvement value of SDS score in the observation group (r =-0.657, P<0.01). CONCLUSION: The ginger-separated moxibustion effectively relieves fatigue and depression condition and improves sleep quality in the patients with chronic fatigue syndrome. The fatigue condition is relevant with sleep quality and depression condition to a certain extent in the patients.

Splenectomy enhances the Ly6Clow phenotype in hepatic macrophages by activating the ERK1/2 pathway during liver fibrosis.

BACKGROUND AND AIM: Splenectomy has been reported to attenuate liver fibrosis. In addition, phenotype transitions of infiltrating macrophages, including Ly6Chigh and Ly6Clow, play an essential role in the liver fibrosis. However, whether the spleen can regulate the phenotype switch of macrophages and the underlying mechanism still remain unclear. METHODS: Chronic liver fibrosis in mice was induced by intraperitoneal injection with carbon tetrachloride. Splenectomy or sham operation was performed with or without depletion of macrophages during liver fibrosis. Liver fibrosis and the proportion of Ly6Chigh and Ly6Clow macrophages were analyzed. Western blotting of ERK1/2 signals was performed in isolated macrophages to investigate the underlying mechanism of phenotype transition. RAW264.7 cells were stimulated by liver total cells conditioned medium with or without preincubation of SCH772984, the ERK1/2 inhibitor, and the phenotype switch of RAW264.7 cells was examined. In vivo, intraperitoneal injection of SCH772984 was performed on the splenectomy mice and the phenotype switch of liver infiltrating macrophages was tested. RESULTS: Splenectomy alleviated the liver inflammation and fibrosis and also promoted the phenotypic switch of infiltrating macrophages to a Ly6Clow phenotype in fibrotic liver. The p-ERK1/2 expression was upregulated in macrophages at the same time. Furthermore, splenectomy increased the percentage of Ly6Clow macrophages and decreased the percentage of Ly6Chigh macrophages both in vivo and in vitro, which was reversed by SCH772984. CONCLUSIONS: Splenectomy attenuates both the liver fibrosis and inflammation, and promotes the phenotype switch of infiltrating macrophages to an anti-inflammatory Ly6Clow phenotype by activating the ERK1/2 pathway during liver fibrosis.

Gasdermin D expression and clinicopathologic outcome in primary osteosarcoma patients.

Gasdermin D (GSDMD), a recently discovered pyroptosis-related protein, has been extensively studied in inflammatory diseases. Research has indicated that inflammation is a causative factor of malignant tumors, including osteosarcoma. Nevertheless, the specific functions of GSDMD in osteosarcoma have not well been studied. This study aimed to explore the clinicopathologic values of GSDMD in osteosarcoma. The expression of GSDMD protein in 41 samples of primary osteosarcoma and 20 normal bone tissues were evaluated by immunohistochemistry and western blot. The χ2 test and Student's t test were applied to analyze the differences of GSDMD expression between osteosarcoma and normal bone tissues. The χ2 test and Fisher's exact test were used to assess the associations of GSDMD expression with clinicopathologic characteristics of osteosarcoma patients. Moreover, the Kaplan-Meier and Cox regression model methods were used to analyze the relations between GSDMD expression and disease-free survival (DFS) and overall survival (OS) of osteosarcoma patients. The GSDMD protein was significantly overexpressed in osteosarcoma compared to non-neoplastic bone samples. Additionally, GSDMD overexpression was related to poor chemotherapy response (P = 0.031), distant metastasis (P < 0.001), as well as worse prognosis of osteosarcoma patients. Furthermore, GSDMD protein overexpression was an independent predictor of poor survival time in primary osteosarcoma patients. In conclusion, GSDMD overexpression was related to adverse clinical outcome of osteosarcoma, and could be a therapy target in osteosarcoma. Further study should focus on the related mechanism of GSDMD in osteosarcoma.

Preferential Homing of Tumor-specific and Functional CD8+ Stem Cell-like Memory T Cells to the Bone Marrow.

The bone marrow (BM) harbors not only hematopoietic stem cells but also conventional memory T and B cells. Studies of BM-resident memory T cells have revealed the complex relationship between BM and immunologic memory. In the present study, we identified CD122 stem cells antigen-1 (Sca-1), B-cell lymphoma protein-2 (Bcl-2), CD8 stem cell-like memory T cells (TSCMs) as a distinct memory T-cell subset preferentially residing in the BM, where these cells respond vigorously to blood-borne antigens. We found that the most TSCMs favorably relocate to the BM by adhesion molecules such as vascular cell adhesion protein 1, P-selectin glycoprotein 1, and P-selectin or E-selectin. Moreover, the BM-resident TSCMs exhibited much higher levels of antitumor activity than the spleen-resident TSCMs. These results indicate that the BM provides an appropriate microenvironment for the survival of CD8 TSCMs, thereby broadening our knowledge of the memory maintenance of antigen-specific CD8 T lymphocytes. The present findings are expected to be instructive for the development of tumor immunotherapy.

Role of Wnt/ß-Catenin Pathway in the Arterial Medial Calcification and Its Effect on the OPG/RANKL System.

In this study, the hypothesis that Wnt/ß-catenin pathway is involved in the arterial calcification by regulating the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) system was tested. The ß-catenin expression was measured in the warfarin-induced calcified arteries and the osteoblast-like cells differentiating from smooth muscle cells (SMCs) by immunohistochemistry and Western blotting. The Wnt/ß-catenin pathway was activated or inhibited by lithium chloride (LiCl) or dickkopf 1 (DKK1) in vitro and in vivo. Then the calcification level was determined by von Kossa staining, Ca2+ content assay, and alkaline phosphatase (ALP) activity assay. The expression levels of osteocalcin, OPG and RANKL were detected by Western blotting or real-time PCR. The results showed that in calcified arteries and OBL cells, the activation of Wnt/ß-catenin pathway significantly enhanced the calcification as evidenced by increased von Kossa stains, Ca2+ contents, ALP activities, and osteocalcin expression levels (P<0.05), and it promoted the RANKL expression (P<0.05), but slightly affected the OPG expression. These results indicated that the activation of Wnt/ß-catenin pathway worsens the arterial calcification, probably by promoting the RANKL expression.

ICAM-1 Deficiency in the Bone Marrow Niche Impairs Quiescence and Repopulation of Hematopoietic Stem Cells.

The bone marrow niche plays a critical role in controlling the fate of hematopoietic stem cells (HSCs) by integrating intrinsic and extrinsic signals. However, the molecular events in the HSC niche remain to be investigated. Here, we report that intercellular adhesion molecule-1 (ICAM-1) maintains HSC quiescence and repopulation capacity in the niche. ICAM-1-deficient mice (ICAM-1-/-) displayed significant expansion of phenotypic long-term HSCs with impaired quiescence, as well as favoring myeloid cell expansion. ICAM-1-deficient HSCs presented normal reconstitution capacity during serial transplantation; however, reciprocal transplantation experiments showed that ICAM-1 deficiency in the niche impaired HSC quiescence and repopulation capacity. In addition, ICAM-1 deletion caused failure to retain HSCs in the bone marrow and changed the expression profile of stroma cell-derived factors, possibly representing the mechanism for defective HSCs in ICAM-1-/- mice. Collectively, these observations identify ICAM-1 as a regulator in the bone marrow niche.

Finasteride Enhances the Generation of Human Myeloid-Derived Suppressor Cells by Up-Regulating the COX2/PGE2 Pathway.

Myeloid-derived suppressor cells (MDSCs) have been known to be a key factor in the regulation of the immune system under numerous conditions such as tumors, infections, autoimmune diseases, and transplantations. In contrast to the proposed deleterious role of MDSCs in tumors and infections, MDSCs with their suppressive function are now proved to have the beneficial potential of suppressing the autoimmune response and promoting tolerance to transplantation. Therefore, the expansion of MDSCs could be a promising therapeutic strategy for many diseases. In this study, we aimed to identify FDA-approved drugs that could aid in the expansion of functional MDSCs. We performed a high-throughput screening (HTS) of FDA-approved drugs based on the in vitro human MDSC-differentiation system and identified finasteride (FIN) to have the best potency to aid the generation of human MDSCs. The FIN-induced MDSCs were quite similar to monocytic MDSCs with regard to their surface phenotype, morphology, immunosuppressive function, and related gene expression. Next, we aimed to determine the mechanism of action of FIN and found that FIN induced the expansion of MDSCs through up-regulation of the COX2/PGE2 pathway by enhancing the activity of COX2 promoter. In addition, the administration of indomethacin (IND), a COX2 inhibitor, abrogated the effect of FIN. Based on these results, we suggested that FIN could find applications in the future in the expansion of MDSCs. Further development of FIN-like compounds could be a novel strategy for generating functional MDSCs for immunosuppressive therapies in various immune disorder conditions.

Host Protein Moloney Leukemia Virus 10 (MOV10) Acts as a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein.

UNLABELLED: The viral ribonucleoprotein (vRNP) complex of influenza A viruses (IAVs) contains an RNA-dependent RNA polymerase complex (RdRp) and nucleoprotein (NP) and is the functional unit for viral RNA transcription and replication. The vRNP complex is an important determinant of virus pathogenicity and host adaptation, implying that its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor of IAV replication, since depletion of MOV10 resulted in a significant increase in virus yield. MOV10 inhibited the polymerase activity in a minigenome system through RNA-mediated interaction with the NP subunit of vRNP complex. Importantly, we found that the interaction between MOV10 and NP prevented the binding of NP to importin-α, resulting in the retention of NP in the cytoplasm. Both the binding of MOV10 to NP and its inhibitory effect on polymerase activity were independent of its helicase activity. These results suggest that MOV10 acts as an anti-influenza virus factor through specifically inhibiting the nuclear transportation of NP and subsequently inhibiting the function of the vRNP complex. IMPORTANCE: The interaction between the influenza virus vRNP complex and host factors is a major determinant of viral tropism and pathogenicity. Our study identified MOV10 as a novel host restriction factor for the influenza virus life cycle since it inhibited the viral growth rate. Conversely, importin-α has been shown as a determinant for influenza tropism and a positive regulator for viral polymerase activity in mammalian cells but not in avian cells. MOV10 disrupted the interaction between NP and importin-α, suggesting that MOV10 could also be an important host factor for influenza virus transmission and pathogenicity. Importantly, as an interferon (IFN)-inducible protein, MOV10 exerted a novel mechanism for IFNs to inhibit the replication of influenza viruses. Furthermore, our study potentially provides a new drug design strategy, the use of molecules that mimic the antiviral mechanism of MOV10.

The function and meaning of receptor activator of NF-κB ligand in arterial calcification.

Osteoclast-like cells are known to inhibit arterial calcification. Receptor activator of NF-κB ligand (RANKL) is likely to act as an inducer of osteoclast-like cell differentiation. However, several studies have shown that RANKL promotes arterial calcification rather than inhibiting arterial calcification. The present study was conducted in order to investigate and elucidate this paradox. Firstly, RANKL was added into the media, and the monocyte precursor cells were cultured. Morphological observation and Tartrate resistant acid phosphatase (TRAP) staining were used to assess whether RANKL could induce the monocyte precursor cells to differentiate into osteoclast-like cells. During arterial calcification, in vivo and in vitro expression of RANKL and its inhibitor, osteoprotegerin (OPG), was detected by real-time PCR. The extent of osteoclast-like cell differentiation was also assessed. It was found RANKL could induce osteoclast-like cell differentiation. There was no in vivo or in vitro expression of osteoclast-like cells in the early stage of calcification. At that time, the ratio of RANKL to OPG was very low. In the late stage of calcification, a small amount of osteoclast-like cell expression coincided with a relatively high ratio of RANKL to OPG. According to the results, the ratio of RANKL to OPG was very low during most of the arterial calcification period. This made it possible for OPG to completely inhibit RANKL-induced osteoclast-like cell differentiation. This likely explains why RANKL had the ability to induce osteoclast-like cell differentiation but acted as a promoter of calcification instead.

Interleukin 7 up-regulates CD95 protein on CD4+ T cells by affecting mRNA alternative splicing: priming for a synergistic effect on HIV-1 reservoir maintenance.

Interleukin-7 (IL-7) has been used as an immunoregulatory and latency-reversing agent in human immunodeficiency virus type 1 (HIV-1) infection. Although IL-7 can restore circulating CD4(+) T cell counts in HIV-1-infected patients, the anti-apoptotic and proliferative effects of IL-7 appear to benefit survival and expansion of HIV-1-latently infected memory CD4(+) T lymphocytes. IL-7 has been shown to elevate CD95 on CD4(+) T cells in HIV-1-infected individuals and prime CD4(+) T lymphocytes to CD95-mediated proliferative or apoptotic signals. Here we observed that through increasing microRNA-124, IL-7 down-regulates the splicing regulator polypyrimidine tract binding protein (PTB), leading to inclusion of the transmembrane domain-encoding exon 6 of CD95 mRNA and, subsequently, elevation of CD95 on memory CD4(+) T cells. Moreover, IL-7 up-regulates cellular FLICE-like inhibitory protein (c-FLIP) and stimulates c-Jun N-terminal kinase (JNK) phosphorylation, which switches CD95 signaling to survival mode in memory CD4(+) T lymphocytes. As a result, co-stimulation through IL-7/IL-7R and FasL/CD95 signal pathways augments IL-7-mediated survival and expansion of HIV-1-latently infected memory CD4(+) T lymphocytes. Collectively, we have demonstrated a novel mechanism for IL-7-mediated maintenance of HIV-1 reservoir.

Effects of carbon monoxide on quality, nutrients and antioxidant activity of post-harvest jujube.

BACKGROUND: To effectively extend the shelf life of fresh jujube, carbon monoxide (CO), as a small molecular gas, was applied to fumigate fresh jujube. The quality and antioxidant activity of jujubes fumigated with carbon monoxide at concentrations of 0 (control), 5, 10, 20 and 40 µmol L⁻¹ for 1 h under ambient temperature were investigated. RESULTS: The jujube fumigated with 10 µmol L⁻¹ CO showed the best preserving effect amongst all samples. At 30 days, the decay incidence of jujube fumigated with 10 µmol L⁻¹ CO is only two-thirds of that of control sample; its red index and weight loss rate were 22.8% and 19.4% lower, and its firmness, soluble solids content (SSC) and acidity were 18.7%, 5.4% and 12.2% higher than that of control samples, respectively. Its vitamin C and total flavonoid contents were also the highest. However, no significant difference in total polyphenol content was found. The jujubes treated with 10 µmol L⁻¹ CO exhibited the highest antioxidant activity in terms of reducing power and 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radical scavenging activity. However, the jujubes fumigated with 40 µmol L⁻¹ CO showed inferior characteristics compared with the control sample. CONCLUSION: Fumigating jujubes with proper concentration of CO probably is a potential novel method for post-harvest jujube preservation in the future.

Carbon Monoxide Fumigation Improved the Quality, Nutrients, and Antioxidant Activities of Postharvest Peach.

Peaches (Prunus persica cv. Yanhong) were fumigated with carbon monoxide (CO) at 0, 0.5, 5, 10, and 20 µmol/L for 2 hours. The result showed that low concentration CO (0.5-10 µmol/L) might delay the decrease of firmness and titrable acid content, restrain the increase of decay incidence, and postpone the variation of soluble solids content, but treating peaches with high concentration CO (20 µmol/L) demonstrated adverse effects. Further research exhibited that exogenous CO could induce the phenylalnine ammonialyase activity, maintain nutrient contents such as Vitamin C, total flavonoid, and polyphenol, and enhance antioxidant activity according to reducing power and 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl radical scavenging activity. Treating peaches with appropriate concentration CO was beneficial to the quality, nutrients, and antioxidant activity of postharvest peaches during storage time. Therefore, CO fumigation might probably become a novel method to preserve postharvest peach and other fruits in the future.

Deficiency of ubiquitin A20 promotes antigen transport across airway epithelial cells via a transcellular pathway.

The epithelial barrier dysfunction is associated with the pathogenesis of a number of diseases. Ubiquitin E3 ligase A20 (A20) plays a critical role in maintaining the homeostasis in the body. This study aimed to investigate the role of A20 in the degradation of endocytic antigens in airway epithelial cells. The expression of A20 in the human nasal epithelial cell line, RPMI 2650 cells (Rpcs), was evaluated. The role of A20 in maintaining the intracellular permeability in Rpc monolayers was assessed in Transwells. The endosome/lysosome fusion in epithelial cells was observed by immunocytochemistry. On the absorption of antigen, the expression of A20 was increased in Rpcs. The knockdown of the A20 gene in Rpcs increased the amounts of the endocytic antigens across the Rpc monolayers. A20 was required in the process of the endosome/lysosome fusion. The antigens transported to the basal compartment by A20-deficient Rpc monolayers still kept strong antigenicity. The nasal epithelial cell line, Rpcs, expresses A20 that facilitates the degradation of endocytic antigens in Rpcs by facilitating the endosome/lysosome fusion.