How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs) are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated in vitro. However, none of current systems for in vitro differentiation of MDSCs have successfully achieved long-term immune tolerance. Herein, we combined dexamethasone (Dex), which is a classic immune regulatory drug in the clinic, with common MDSCs inducing cytokine granulocyte macrophage colony stimulating factor (GM-CSF) to generate MDSCs in vitro. Addition of Dex into GM-CSF system specifically increased the number of CD11b+ Gr-1int/low MDSCs with an enhanced immunosuppressive function in vitro. Adoptive transfer of these MDSCs significantly prolonged heart allograft survival and also favored the expansion of regulatory T cells in vivo. Mechanistic studies showed that inducible nitric oxide sythase (iNOS) signaling was required for MDSCs in the control of T-cell response and glucocorticoid receptor (GR) signaling played a critical role in the recruitment of transferred MDSCs into allograft through upregulating CXCR2 expression on MDSCs. Blockade of GR signaling with its specific inhibitor or genetic deletion of iNOS reversed the protective effect of Dex-induced MDSCs on allograft rejection. Together, our results indicated that co-application of Dex and GM-CSF may be a new and important strategy for the induction of potent MDSCs to achieve immune tolerance in organ transplantation.

This study was aimed to estimate the prevalences of chlamydia (CT) and gonococcal (NG) infections and explore risk factors associated with the CT infection among women in Shenzhen, China. We collected socio-demographic and clinical data from women (aged 20–60) and determined positivity of CT or NG by nucleic acid amplification test (NAAT) with self-collected urine specimens. We estimated prevalence of CT and NG and determined risk factors associated with CT infection. Among 9,207 participants, 4.12% (95% confidence interval [CI], 3.71%-4.53%) tested positive for CT and 0.17% (95% CIs, 0.09%-0.25%) for NG. Factors significantly associated with CT infection included being an ethnic minority (ethnicity other than Han China) (Adjusted odds ratio [AOR], 1.9; 95% CI, 1.2–3.0), using methods other than condom for contraception (AOR, 1.5; 95% CI, 1.2–1.8), having a history of adverse pregnancy outcomes (AOR, 1.4; 95% CI, 1.1–1.8), and experiencing reproductive tract symptoms in the past three months (AOR, 1.3; 95% CI, 1.0–1.7). we found that CT infection is prevalent among women in Shenzhen, China and associated with both demographic and behavioral factors. A comprehensive CT screening, surveillance and treatment programme targeting this population is warranted.

The asparagine (N)-linked Man9GlcNAc2 is required for glycoprotein folding and secretion. Understanding how its structure contributes to these functions has been stymied by our inability to produce this glycan as a homogenous structure of sufficient quantities for study. Here, we report the high yield chemoenzymatic synthesis of Man9GlcNAc2 and its biosynthetic intermediates by reconstituting the eukaryotic lipid-linked oligosaccharide (LLO) pathway. Endoplasmic reticulum mannosyltransferases (MTases) are expressed in E. coli and used for mannosylation of the dolichol mimic, phytanyl pyrophosphate GlcNAc2. These recombinant MTases recognize unique substrates and when combined, synthesize end products that precisely mimic those in vivo, demonstrating that ordered assembly of LLO is due to the strict enzyme substrate specificity. Indeed, non-physiological glycans are produced only when the luminal MTases are challenged with cytosolic substrates. Reconstitution of the LLO pathway to synthesize Man9GlcNAc2 in vitro provides an important tool for functional studies of the N-linked glycoprotein biosynthesis pathway.

Asparagine (N)-linked glycosylation is one of the most common co-and post-translational modifications of both intra-and extracellularly distributing proteins, which directly affects their biological functions, such as protein folding, stability and intercellular traffic. Production of the structural well-defined homogeneous N-glycans contributes to comprehensive investigation of their biological roles and molecular basis. Among the various methods, chemo-enzymatic approach serves as an alternative to chemical synthesis, providing high stereoselectivity and economic efficiency. This review summarizes some recent advances in the chemo-enzymatic methods for the production of N-glycans, including the preparation of substrates and sugar donors, and the progress in the glycosyltransferases characterization which leads to the diversity of N-glycan synthesis. We discuss the bottle-neck and new opportunities in exploiting the chemo-enzymatic synthesis of N-glycans based on our research experiences. In addition, downstream applications of the constructed N-glycans, such as automation devices and homogeneous glycoproteins synthesis are also described.

Background:Recent studies have suggested that the presence of a pathological fracture does not impact on oncologic outcomes and the feasibility of limb salvage surgery (LSS) in appropriately selected patients when combined with neoadjuvant chemotherapy. These have largely been single institutional studies with limited numbers. The Eastern Asian Musculoskeletal Oncology Group reviewed the data from three large volume Asian orthopedic oncology centers to determine whether the presence of a pathologic fracture affected outcomes in osteosarcoma patients.Methods:A retrospective review of the data was conducted. Ninety-five cases of nonmetastatic extremity osteosarcoma with a pathological fracture and 887 cases without fracture treated during the same period were compared.Results:In the fracture group, the LSS rate was 62.1%, and the rate of amputation was 37.9%. In the nonfracture group, the LSS rate was 74.7%, and the amputation was 25.3%. In patients with a pathologic fracture, the rate of local recurrence for LSS and amputation groups was 8.5% and 2.8%, respectively. In this group, the 5-year survival in the LSS group was 66% as against. 46.8% in the amputation group.Conclusions:Our study suggests that surgically treated patients with pathologic fractures in osteosarcoma have adequate local control and do not have a poorer outcome compared to patients without a fracture. Though osteosarcoma with a pathologic fracture is not a contraindication for limb salvage, appropriate case selection is important when deciding local control options to ensure adequate oncologic clearance.