Pomelo peel biomass derived highly active advanced-oxidation-process catalyst: Complete elimination of organic pollutants.

The advanced oxidation process (AOPs) is playing an important role in the elimination of hazardous organic pollutants, but the development of inexpensive and highly active advanced catalysts is facing challenges. In this study, a low-cost and readily available agricultural waste resource pomelo peel-flesh (PPF) biomass was used as the basic raw material, and the uniformly dispersed small cobalt nanoparticles were effectively anchored in the biochar derived from pomelo peel-flesh (BDPPF) by impregnation adsorption/complexation combined with heat treatment. Co/BDPPF (BDPPF embedded with Co) can effectively activate peroxymonosulfate (PMS) to SO4·-, ·OH and 1O2 reactive oxygen species, and achieve nearly 100% degradation of tetracycline persistent organic pollutant. Co/BDPPF can not only degrade tetracycline efficiently in complex water environment, but also degrade most organic pollutants universally, and has long-term stability, which solves the problem of poor universality and stability of heterogeneous catalysts to a certain extent. Importantly, Co/BDPPF derived from waste biomass was also innovatively designed as the core of an integrated continuous purification device to achieve continuous purification of organic wastewater. In this study, agricultural waste resources were selected as biomass raw materials to achieve efficient capture of Co2+, and finally developed advanced AOPs catalyst with excellent performance to achieve the purification of organic wastewater. It also provides a promising solution for the preparation of simple, low-cost, large-scale production of AOPs catalysts that can be put into actual production.

Parental betaine supplementation promotes gosling growth with epigenetic modulation of IGF gene family in the liver.

Betaine is widely used as a feed additive in the chicken industry to promote laying performance and growth performance, yet it is unknown whether betaine can be used in geese to improve the laying performance of goose breeders and the growth traits of offspring goslings. In this study, laying goose breeders at 39 wk of age were fed basal (Control, CON) or betaine-supplemented diets at low (2.5 g/kg, LBT) or high (5 g/kg, HBT) levels for 7 wk, and the breeder eggs laid in the last week were collected for incubation. Offspring goslings were examined at 35 and 63 d of age. The laying rate tended to be increased (P = 0.065), and the feed efficiency of the breeders was improved by betaine supplementation, while the average daily gain of the offspring goslings was significantly increased (P < 0.05). Concentrations of insulin-like growth factor 2 (IGF-2) in serum and liver were significantly increased in the HBT group (P < 0.05), with age-dependent alterations of serum T3 levels. Concurrently, hepatic mRNA expression of the IGF gene family was significantly increased in goslings derived from betaine-treated breeders (P < 0.05). A higher ratio of proliferating cell nuclear antigen (PCNA)-immunopositive nuclei was found in the liver sections of the HBT group, which was confirmed by significantly upregulated hepatic expression of PCNA mRNA and protein (P < 0.05). Moreover, hepatic expression of thyroxine deiodinase type 1 (Dio1) and thyroid hormone receptor ß (TRß) was also significantly upregulated in goslings of the HBT group (P < 0.05). These changes were associated with significantly higher levels of global DNA 5-mC methylation, together with increased expression of methyl transfer genes (P < 0.05), including betaine-homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT), and DNA (cytosine-5-)-methyltransferase 1 (DNMT1). The promoter regions of IGF-2 genes, as well as the predicted TRß binding site on the IGF-2 gene, were significantly hypomethylated (P < 0.05). These results indicate that gosling growth can be improved by dietary betaine supplementation in goose breeders via epigenetic modulation of the IGF gene family, especially IGF-2, in the liver.

The goose industry plays important roles in economics, cultures, and ecosystems, yet the low laying and growth rates of many indigenous breeds hinders the development of the goose farming. Betaine, an important methyl donor, is commonly used as a feed additive in livestock and poultry to enhance animal growth. Dietary supplementation of betaine in laying hens or gestational sows has been reported to promote the growth of their offspring. Here, we sought to investigate whether and how dietary betaine supplementation affects the growth and development of offspring goslings. In this study, goose breeders, both male and female, were fed a basal diet supplemented respectively with 0, 2.5, or 5 g/kg betaine for 7 wk. Goslings hatched from the breeder eggs of different groups were raised under the same standard condition for assessing the growth performance. Parental betaine increases the growth rate of offspring goslings with decreased DNA methylation on the IGF-2 gene promoter and increased expression of the IGF-2 gene in the liver. These results provide scientific evidence for the inter-generational effect of betaine on gosling growth.

Unveiling Cutting-Edge Developments in Electrocatalytic Nitrate-to-Ammonia Conversion.

The excessive enrichment of nitrate in the environment can be converted into ammonia (NH3) through electrochemical processes, offering significant implications for modern agriculture and the potential to reduce the burden of the Haber-Bosch (HB) process while achieving environmentally friendly NH3 production. Emerging research on electrocatalytic nitrate reduction (eNitRR) to NH3 has gained considerable momentum in recent years for efficient NH3 synthesis. However, existing reviews on nitrate reduction have primarily focused on limited aspects, often lacking a comprehensive summary of catalysts, reaction systems, reaction mechanisms, and detection methods employed in nitrate reduction. This review aims to provide a timely and comprehensive analysis of the eNitRR field by integrating existing research progress and identifying current challenges. This review offers a comprehensive overview of the research progress achieved using various materials in electrochemical nitrate reduction, elucidates the underlying theoretical mechanism behind eNitRR, and discusses effective strategies based on numerous case studies to enhance the electrochemical reduction from NO3 - to NH3. Finally, this review discusses challenges and development prospects in the eNitRR field with an aim to guide design and development of large-scale sustainable nitrate reduction electrocatalysts.

Altered sphingolipid pathway in SARS-CoV-2 infected human lung tissue.

Introduction: The SARS-CoV-2 mediated COVID-19 pandemic has impacted millions worldwide. Hyper-inflammatory processes, including cytokine storm, contribute to long-standing tissue injury and damage in COVID-19. The metabolism of sphingolipids as regulators of cell survival, differentiation, and proliferation has been implicated in inflammatory signaling and cytokine responses. Sphingosine-kinase-1 (SK1) and ceramide-synthase-2 (CERS2) generate metabolites that regulate the anti- and pro-apoptotic processes, respectively. Alterations in SK1 and CERS2 expression may contribute to the inflammation and tissue damage during COVID-19. The central objective of this study is to evaluate structural changes in the lung post-SARS-CoV-2 infection and to investigate whether the sphingolipid rheostat is altered in response to SARS-CoV-2 infection. Methods: Central and peripheral lung tissues from COVID-19+ or control autopsies and resected lung tissue from COVID-19 convalescents were subjected to histologic evaluation of airspace and collagen deposisiton, and immunohistochemical evaluation of SK1 and CERS2. Results: Here, we report significant reduction in air space and increase in collagen deposition in lung autopsy tissues from patients who died from COVID-19 (COVID-19+) and COVID-19 convalescent individuals. SK1 expression increased in the lungs of COVID-19+ autopsies and COVID-19 convalescent lung tissue compared to controls and was mostly associated with Type II pneumocytes and alveolar macrophages. No significant difference in CERS2 expression was noted. SARS-CoV-2 infection upregulates SK1 and increases the ratio of SK1 to CERS2 expression in lung tissues of COVID-19 autopsies and COVID-19 convalescents. Discussion: These data suggest an alteration in the sphingolipid rheostat in lung tissue during COVID-19, suggesting a potential contribution to the inflammation and tissue damage associated with viral infection.

Factors Associated With HIV Testing Among MSM in Guilin, China: Results From a Cross-Sectional Study.

Objectives: The objective of this study is to explore factors affecting the HIV testing behaviors among men who have sex with men (MSM) in China. Methods: A cross-sectional study was conducted in Guilin, China from April to June of 2021. Questionnaire data of 300 MSM were analyzed, and binary logistic regression models were used to examine the socio-demographic and sexual behavior characteristics associated with three HIV testing behaviors (self-testing, institutional testing, and regular testing). Results: The results showed that half of the respondents had the habit of regular HIV testing. Only 30.0% of MSM chose to do HIV testing after high-risk sexual behavior, and self-perceived luck was the main reason for not having HIV testing. Moreover, the influencing factors of three HIV testing behaviors after high-risk sexual behavior differ. Interestingly, income was not related to any of the three HIV testing behaviors among those MSM who participated. Conclusion: This research indicates insufficient health education on HIV testing behaviors among MSM in China. Health promotion practices targeting the MSM population to improve HIV-related knowledge, thus contributing to the HIV epidemic, are required.

The role of SPI1-TYROBP-FCER1G network in oncogenesis and prognosis of osteosarcoma, and its association with immune infiltration.

Osteosarcoma is an aggressive malignant bone sarcoma worldwide. A causal gene network with specific functions underlying both the development and progression of OS was still unclear. Here we firstly identified the differentially expressed genes (DEGs) between control and OS samples, and then defined the hub genes and top clusters in the protein-protein interaction (PPI) network of these DEGs. By focusing on the hub gene TYROBP in the top 1 cluster, a conserved TYROBP co-expression network was identified. Then the effect of the network on OS overall survival was analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and Gene Set Enrichment Analysis (GSEA) were used to explore the functions of the network. XCell platform and ssGSEA algorithm were conducted to estimate the status of immune infiltration. ChEA3 platform, GSEA enrichment analysis, and Drug Pair Seeker (DPS) were used to predict the key transcription factor and its upstream signal. We identified the downregulated SPI1-TYROBP-FCER1G network in OS, which were significantly enriched in immune-related functions. We also defined a two-gene signature (SPI1/FCER1G) that can predict poorer OS overall survival and the attenuated immune infiltration when downregulated. The SPI1-TYROBP-FCER1G network were potentially initiated by transcription factor SPI1 and would lead to the upregulated CD86, MHC-II, CCL4/CXCL10/CX3CL1 and hence increased immune infiltrations. With this study, we could better explore the mechanism of OS oncogenesis and metastasis for developing new therapies.

A Peptide-Based Enzyme-Linked Immunosorbent Assay for Detecting Antibodies Against Avian Infectious Bronchitis Virus.

Infectious bronchitis virus (IBV) causes substantial loss to the poultry industry despite extensive vaccination. Assessing the antibody response is important for the development and evaluation of effective vaccines. We have developed an enzyme-linked immunosorbent assay (ELISA) for the detection of IBV-specific antibodies, using a synthetic peptide based on a conserved sequence in the IBV spike protein. This peptide-based ELISA (pELISA) specifically detects antibodies to different genotypes of IBV but not antibodies against other common chicken viruses. This assay could detect IBV-specific antibody response on as early as day 7 postinfection. In the testing with field serum samples collected from chickens administered with IBV vaccines, the sensitivity, specificity, and accuracy of pELISA were 98.30, 94.12, and 98.8%, respectively, relative to indirect immunofluorescence assay. Our data demonstrate that the pELISA is of value for the detection of IBV antibody and the evaluation of IBV vaccines.

Efficacy and safety of accelerated partial breast irradiation: a meta-analysis of published randomized studies.

BACKGROUND AND PURPOSE: Accelerated partial breast irradiation (APBI) technology has theoretical advantages in comparison with traditional adjuvant radiation therapy (whole-breast irradiation; WBI) after breast-conserving surgery. However, published randomized controlled trials have shown inconsistent outcomes. Therefore, a comprehensive assessment of the effectiveness and safety of APBI technology is needed. RESULTS: A total of 7 studies of 7452 patients were included in this analysis. All 7 studies reported local recurrence as an outcome. Meta-analysis of 5 trials that included 6486 patients showed significantly different 5-year local recurrence rates for APBI and WBI groups (hazard ratio = 4.54, 95% confidence interval: 1.78-11.61, p = 0.002). Further analysis showed that this difference may be related to the choice of treatment methods. Benefit was conferred to the APBI group for the outcome of non-breast cancer deaths. There was no significant difference between the two groups in terms of nodal recurrence, systemic recurrence, overall survival, or mortality rates. Toxicity side effects and cosmetic effects were similar in both groups, but intraoperative radiotherapy seemed to have a greater acute response. MATERIAL AND METHODS: Searches for relevant randomized controlled trials of APBI versus WBI were performed using the following sources: PubMed, EMBASE, Cochrane Library, Web of Science. Two independent observers evaluated the identified studies. The meta-analysis was conducted using RevMan 5.2 software. CONCLUSIONS: Although the analysis showed that patients receiving APBI had a higher local recurrence rate, subgroup analyses suggested that this might be related to treatment options. Patients who receive accurate radiotherapy may have greater benefits. APBI is a promising treatment technology and more phase III clinical trials are expected based on new treatments.

Novel avian leukosis viruses from domestic chicken breeds in mainland China.

Two novel avian leukosis viruses (ALVs) were isolated from 1380 whole blood samples taken from domestic chicken breeds in China. The two ALVs were uniquely different from the env (Envelope) genes of ALV A-J and carried an LTR (long terminal repeat) cluster from ALV-E. Large scale sequence analysis further showed that these ALVs (with different env and LTRs) were recently endemic in domestic chicken breeds in both China and Japan. The emergence of these novel ALVs is challenging the current ALV eradication program, and as such novel ALVs should be monitored in a timely and careful manner to stop their transmission and further recombination in the future.

CHD7 interacts with BMP R-SMADs to epigenetically regulate cardiogenesis in mice.

Haploinsufficiency for CHD7, an ATP-dependent nucleosome remodeling factor, is the leading cause of CHARGE syndrome. While congenital heart defects (CHDs) are major clinical features of CHARGE syndrome, affecting >75% of patients, it remains unclear whether CHD7 can directly regulate cardiogenic genes in embryos. Our complementary yeast two-hybrid and biochemical assays reveal that CHD7 is a novel interaction partner of canonical BMP signaling pathway nuclear mediators, SMAD1/5/8, in the embryonic heart. Moreover, CHD7 associates in a BMP-dependent manner with the enhancers of a critical cardiac transcription factor, Nkx2.5, that contain functional SMAD1-binding elements. Both the active epigenetic signature of Nkx2.5 regulatory elements and its proper expression in cardiomyocytes require CHD7. Finally, inactivation of Chd7 in mice impairs multiple BMP signaling-regulated cardiogenic processes. Our results thus support the model that CHD7 is recruited by SMAD1/5/8 to the enhancers of BMP-targeted cardiogenic genes to epigenetically regulate their expression. Impaired BMP activities in embryonic hearts may thus have a major contribution to CHDs in CHARGE syndrome.

Exosome-like nanoparticles from intestinal mucosal cells carry prostaglandin E2 and suppress activation of liver NKT cells.

Regulation and induction of anergy in NKT cells of the liver can inhibit autoimmune and antitumor responses by mechanisms that are poorly understood. We investigated the effects of PGE2, delivered by intestinal, mucus-derived, exosome-like nanoparticles (IDENs), on NKT cells in mice. In this study, we demonstrate that IDENs migrate to the liver where they induce NKT cell anergy. These effects were mediated by an IDENs' PGE2. Blocking PGE2 synthesis attenuated IDENs inhibition of induction of IFN-γ and IL-4 by α-galactosylceramide (α-GalCer)-stimulated liver NKT cells in a PGE2 E-type prostanoid 2/E-type prostanoid 4 receptor-mediated manner. Proinflammatory conditions enhanced the migration of IDENs to the liver where α-GalCer and PGE2 induced NKT anergy in response to subsequent α-GalCer stimulation. These findings demonstrate that IDENs carrying PGE2 can be transferred from the intestine to the liver, where they act as immune modulators, inducing an anergic-like state of NKT cells. These reagents might be developed as therapeutics for autoimmune liver diseases.

TLR2-mediated expansion of MDSCs is dependent on the source of tumor exosomes.

Exosomes released from tumor cells having been shown to induce interleukin-6 release from myeloid-derived suppressor cells in a Toll-like receptor 2/Stat3-dependent manner. In this study, we show that exosomes released from tumor cells re-isolated from syngeneic mice are capable of inducing interleukin-6 in a Toll-like receptor 2-independent manner, whereas the data generated from exosomes of tumor cells having undergone numerous in vitro passages induce interleukin-6 in a Toll-like receptor 2-dependent manner. This discrepancy may be due to the source of tumor cells used to generate the exosomes for this study. These results suggest that exosomes released from tumor cells that are not within a tumor microenvironment may not realistically represent the role of tumor exosomes in vivo. This is an important consideration since frequently passing tumor cells in vivo is an accepted practice for studying tumor exosome-mediated inflammatory responses.

A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.

Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood. We show that the target specificity is determined by exosomes, and the improvement of curcumin activity is achieved by directing curcumin to inflammatory cells associated with therapeutic, but not toxic, effects. Furthermore, we validate the therapeutic relevance of this technique in a lipopolysaccharide (LPS)-induced septic shock mouse model. We further show that exosomes, but not lipid alone, are required for the enhanced anti-inflammatory activity of curcumin. The specificity of using exosomes as a drug carrier creates opportunities for treatments of many inflammation-related diseases without significant side effects due to innocent bystander or off-target effects.

Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells.

In this study we observed that mice pretreated with tumor exosomes had a significant acceleration of tumor metastasis in the lung. Tumor metastasis correlated significantly with an increase in recruitment of more Myeloid-derived suppressor cells (MDSCs) in the lung of C57BL/6j (B6) mice pretreated with tumor exosomes. These effects were blunted when MyD88 knockout (KO) mice were pretreated with tumor exosomes. MDSCs induced by tumor exosomes and isolated from wild-type B6 mice also more potently inhibited T cell activation and induction of interleukin-6 and tumor necrosis factor-alpha than MDSCs isolated from the lung of MyD88 KO mice. In vitro, addition of tumor exosomes to bone marrow-derived CD11b(+)Gr-1(+) cells isolated from wild-type B6 mice resulted in more cytokine production, including tumor necrosis factor-alpha, interleukin-6, and the chemokine CCL2, than CD11b(+)Gr-1(+) cells isolated from MyD88 KO mice. Moreover, lower levels of CCL2 were observed in the lungs in MyD88 KO mice pretreated with tumor exosomes than that in wild-type mice. Together these data demonstrate a pivotal role for MyD88 in tumor exosome-mediated expansion of MDSCs and tumor metastasis.

Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance.

OBJECTIVE: We sought to determine whether exosome-like vesicles (ELVs) released from adipose tissue play a role in activation of macrophages and subsequent development of insulin resistance in a mouse model. RESEARCH DESIGN AND METHODS: ELVs released from adipose tissue were purified by sucrose gradient centrifugation and labeled with green fluorescent dye and then intravenously injected into B6 ob/ob mice (obese model) or B6 mice fed a high-fat diet. The effects of injected ELVs on the activation of macrophages were determined through analysis of activation markers by fluorescence-activated cell sorter and induction of inflammatory cytokines using an ELISA. Glucose tolerance and insulin tolerance were also evaluated. Similarly, B6 mice with different gene knockouts including TLR2, TLR4, MyD88, and Toll-interleukin-1 receptor (TIR) domain-containing adaptor protein inducing interferon-beta (TRIF) were also used for testing their responses to the injected ELVs. RESULTS: ELVs are taken up by peripheral blood monocytes, which then differentiate into activated macrophages with increased secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Injection of obELVs into wild-type C57BL/6 mice results in the development of insulin resistance. When the obELVs were intravenously injected into TLR4 knockout B6 mice, the levels of glucose intolerance and insulin resistance were much lower. RBP4 is enriched in the obELVs. Bone marrow-derived macrophages preincubated with recombinant RBP4 led to attenuation of obELV-mediated induction of IL-6 and TNF-alpha. CONCLUSIONS: ELVs released by adipose tissue can act as a mode of communication between adipose tissues and macrophages. The obELV-mediated induction of TNF-alpha and IL-6 in macrophages and insulin resistance requires the TLR4/TRIF pathway.

Immature myeloid cells induced by a high-fat diet contribute to liver inflammation.

UNLABELLED: Chronic inflammation plays a critical role in promoting obesity-related disorders, such as fatty liver disease. The inflammatory cells that mediate these effects remain unknown. This study investigated the accumulation of immature myeloid cells in the liver and their role in liver inflammation. We found that the accumulation of immature myeloid cells, i.e., CD11b(+)Ly6C(hi)Ly6G(-) cells, in the liver of B6 mice fed a high-fat diet contribute to liver inflammation. Adoptive transfer of CD11b(+)Ly6C(hi)Ly6G(-) cells isolated from the liver of obese B6 mice, but not from lean B6 mice, resulted in liver damage that was evident by an increase in the activity of liver transferases in serum. CD11b(+)Ly6C(hi)Ly6G(-) cells isolated from the liver of obese mice are more easily activated by way of Toll-like receptor (TLR) stimulation resulting in interleukin 12 and other inflammatory cytokine expression in an MyD88-dependent fashion. TLR7-activated CD11b(+)Ly6C(hi)Ly6G(-) cells also enhance liver natural killer T cell (NKT) death in an Fas-dependent manner. Experiments using mice depleted of Gr-1(+) immature myeloid cells demonstrated the important role of CD11b(+)Ly6C(hi)Ly6G(-) in liver inflammation. Repeated injection of exosome-like particles causes CD11b(+) cell activation and subsequent homing to and accumulation of the cells in the liver. CONCLUSION: Consumption of a high-fat diet by B6 mice triggers an accumulation of immature myeloid cells in the liver. The immature myeloid cells release proinflammatory cytokines and induce NKT cell apoptosis. Activation-induced NKT apoptosis further promotes excessive production of Th-1 cytokines. This diet-induced accumulation of immature myeloid cells may contribute to obesity-related liver disease.

Induction of myeloid-derived suppressor cells by tumor exosomes.

Myeloid-derived suppressor cells (MDSCs) promote tumor progression. The mechanisms of MDSC development during tumor growth remain unknown. Tumor exosomes (T-exosomes) have been implicated to play a role in immune regulation, however the role of exosomes in the induction of MDSCs is unclear. Our previous work demonstrated that exosomes isolated from tumor cells are taken up by bone marrow myeloid cells. Here, we extend those findings showing that exosomes isolated from T-exosomes switch the differentiation pathway of these myeloid cells to the MDSC pathway (CD11b(+)Gr-1(+)). The resulting cells exhibit MDSC phenotypic and functional characteristics including promotion of tumor growth. Furthermore, we demonstrated that in vivo MDSC mediated promotion of tumor progression is dependent on T-exosome prostaglandin E2 (PGE2) and TGF-beta molecules. T-exosomes can induce the accumulation of MDSCs expressing Cox2, IL-6, VEGF, and arginase-1. Antibodies against exosomal PGE2 and TGF-beta block the activity of these exosomes on MDSC induction and therefore attenuate MDSC-mediated tumor-promoting ability. Exosomal PGE2 and TGF-beta are enriched in T-exosomes when compared with exosomes isolated from the supernatants of cultured tumor cells (C-exosomes). The tumor microenvironment has an effect on the potency of T-exosome mediated induction of MDSCs by regulating the sorting and the amount of exosomal PGE2 and TGF-beta available. Together, these findings lend themselves to developing specific targetable therapeutic strategies to reduce or eliminate MDSC-induced immunosuppression and hence enhance host antitumor immunotherapy efficacy.

COP9-associated CSN5 regulates exosomal protein deubiquitination and sorting.

Ubiquitinated endosomal proteins that are deposited into the lumens of multivesicular bodies are either sorted for lysosomal-mediated degradation or secreted as exosomes into the extracellular milieu. The mechanisms that underlie the sorting of cellular cargo proteins are currently unknown. In this study, we show that the COP9 signalosome (CSN)-associated protein CSN5 quantitatively regulated proteins that were sorted into exosomes. Western blot analysis of exosomal proteins indicated that small interfering (si)RNA knockdown of CSN5 results in increased levels of both ubiquitinated and non-ubiquitinated exosomal proteins, including heat shock protein 70, in comparison with exosomes isolated from the supernatants of 293 cells transfected with scrambled siRNA. Furthermore, 293 cells transfected with JAB1/MPN/Mov34 metalloenzyme domain-deleted CSN5 produced exosomes with higher levels of ubiquitinated heat shock protein 70, which did not affect non-ubiquitinated heat shock protein 70 levels. The loss of COP9-associated deubiquitin activity of CSN5 also led to the enhancement of HIV Gag that was sorted into exosomes as well as the promotion of HIV-1 release, suggesting that COP9-associated CSN5 regulates the sorting of a number of exosomal proteins in both a CSN5 JAB1/MPN/Mov34 metalloenzyme domain-dependent and -independent manner. We propose that COP9-associated CSN5 regulates exosomal protein sorting in both a deubiquitinating activity-dependent and -independent manner, which is contrary to the current idea of ubiquitin-dependent sorting of proteins to exosomes.

Tetra-ethyl-ammonium dicyanidobis(ethane-1,2-dithiol-ato)tetra-µ(3)-sulfido-dimolybdenum(V)dicopper(I).

The title compound, (C(8)H(20)N)(2)[Cu(2)Mo(2)(C(2)H(4)S(2))(2)(CN)(2)S(4)], is a sulfide-bridged tetranuclear complex in which the complex anion comprises one [(edt)(2)Mo(2)S(2)(µ-S)(2)](2-) unit (edt = ethanedithiol-ate) and two CuCN units joined through six Cu-µ(3)-S bonds, thus forming a cubane-like [Mo(2)S(4)Cu(2)] core. There are two independent cation-anion complex entities in the asymmetric unit. Bond distances are normal for this type of complex [ranges: Mo-S = 2.193 (2)-2.390 (2); Cu-S = 2.266 (2)-2.470 (2); Cu-C = 1.899 (7)-1.911 (9) Å]. One of the thiol-ato C atoms is disordered over two sites in a 0.52 (3):0.48 (3) ratio.