Search

Abstract Patients diagnosed with acute respiratory distress syndrome are generally severely distressed and associated with high morbidity and mortality despite aggressive treatments such as extracorporeal membrane oxygenation (ECMO) support. To identify potential biomarker of predicting value for appropriate use of this intensive care resource, plasma interleukin-10 along with relevant inflammatory cytokines and immune cell populations were examined during the early and subsequent disease courses of 51 critically ill patients who received ECMO support. High interleukin-10 levels at the time of ECMO installation and during the first 6 hours after ECMO support of these patients stand as a promising biomarker associated with grave prognosis. The initial interleukin-10 level is correlated to other conventional risk evaluation scores as a predictive factor for survival, and furthermore, elevated interleukin-10 levels are also related to a delayed recovery of certain immune cell populations such as CD14+CD16+, CD14+TLR4+ monocytes, and T regulator cells. Genetically, high interleukin-10 is associated to two polymorphic nucleotides (−592 C and −819 C) at the interleukin-10 gene promoter area. Our finding provides prognostic and mechanistic information on the outcome of severely respiratory distressed patients, and potentially paves the strategy to develop new therapeutic modality based on the principles of precision medicine.

Cytotoxic T cells (CTLs) bind to peptides presented by MHC I (pMHC) through T cell receptors of various affinities. Low-affinity CTLs are important for the control of intracellular pathogens and cancers; however, the mechanisms by which these lower affinity CTLs are activated and maintained are not well understood. We recently discovered that fully activated CTLs stimulated by strong-affinity peptides in the presence of IL-12 are able to secrete exosomes that, in turn, stimulate bystander CTLs without requiring the presence of antigen. We hypothesized that exosomes secreted by high-affinity CTLs could strengthen the activation of low-affinity CTLs. Naive OT-I CD8+ cells were stimulated with altered N4 peptides of different affinities in the presence or absence of Exo. The presence of Exo preferentially increased cell proliferation and enhanced the production of IFNγ in CTLs stimulated by low-affinity peptides. The expression of granzyme B (GZB) was augmented in all affinities, with higher GZB production in low-affinity stimulated CTLs than in high-affinity stimulated ones. Exosomes promoted the rapid activation of low-affinity CTLs, which remained responsive to exosomes for a prolonged duration. Unexpectedly, exosomes could be induced quickly (24 h) following CTL activation and at a higher quantity per cell than later (72 h). While exosome protein profiles vary significantly between early exosomes and their later-derived counterparts, both appear to have similar downstream functions. These results reveal a potential mechanism for fully activated CTLs in activating lower-affinity CTLs that may have important implications in boosting the function of low-affinity CTLs in immunotherapy for cancers and chronic viral infections.

Past immunological studies in broilers focused on juveniles within the rapid pre-slaughter growth period and may not reflect adult immune responses, particularly in breeders managed with chronic feed restriction (R). The study aimed to assess innate immune cell functions in respect to R vs. ad libitum (Ad) feed intake in breeder hens with and without dietary 25-hydroxycholecalciferol (25-OH-D3) supplementation. Ad-feed intake consistently suppressed IL-1β secretion, respiratory burst, and cell livability in peripheral heterophils and/or monocytes along the feeding trial from the age of 51 to 68 weeks. Supplemental 25-OH-D3 repressed IL-1β secretion and respiratory burst of both cells mostly in R-hens, but promoted monocyte phagocytosis, chemotaxis, and bacterial killing activity in Ad-hens in accompany with relieved hyperglycemia, hyperlipidemia, and systemic inflammation. Overnight cultures with leukocytes from R-hens confirmed the differential effects of 25-OH-D3 to rescue immune functions altered by glucose and/or palmitic acid exposure. Studies with specific inhibitors further manifested the operative mechanisms via glucolipotoxicity in a cell type- and function-dependent manner. The results concluded no predominant changes between R- vs. Ad-feed intake on leukocyte defense against pathogens despite some differential differences, but supplemental 25-OH-D3 exerts more pronounced effects in Ad-hens.

The success of many endosseous implants in orthopaedic and dental applications depends on the surface characteristics, as they affect osseous integration. Previous investigations indicated that a novel large-grit sand-blasted and acid-etched (SLA) titanium (denoted as SLAffinity-Ti) implant had better bone integration than that of a comparably shaped implant with a plasma-sprayed titanium surface. The purpose of the present investigation was to create a SLAffinity surface on pedicle screws and trauma screws and to compare it with the surfaces of a sand-blasted-only implant and commercial implants in terms of bone integration. The cortical bone and spine of twelve minipigs were implanted with 3 and 4 implants, respectively, and the bone integration was evaluated using micro-computed tomography (micro-CT), mechanical tests (pull-out strength and stripping torque), and histological analysis (toluidine blue and hematoxylin and eosin staining) one and three months after implantation. The micro-CT images showed that the gap between the bone and implant was consistently higher in the sand-blasted-only and commercial groups compared to that in the SLAffinity group 1 and 3 months after implantation. Moreover, the bone volume of implant inserted into bone and the percentage of implant inside bone tissue were greater in the SLAffinity screws 1 and 3 months after implantation, as compared to the sand-blasted and commercial screws. In the mechanical tests, the removal torque and pull-out strength (p < 0.05) were higher in the SLAffinity group at 1 and 3 months. The histological results were consistent with mechanical testing, showing that the SLAffinity group had the most mineralized matrix, the most bone formation around the screws, and the most bone cells in bone tissue. These findings indicate that a SLAffinity surface can effectively enhance the holding strength and integration of pedicle screws and cortical screws, promoting early healing and improving outcomes, compared to sand-blasted-only and commercial implants.

Stable osseointegration between implant threads and the surrounding marginal bone provides the mechanical base of an implant for daily chewing activity. The contact area of implant-bone interfaces and the concentrated stresses on the marginal bones are principal concerns of implant designers. The purpose of this study was to investigate the effects of thread shape and taper on the initial stability of the implant-bone structure. Materials and methods: The thread design was parameterized by shape and taper. Thread shapes included symmetrical, square, and buttressed. Thread tapers were divided into cylindrical and conical profiles. Nine variations of the thread design were developed to numerically evaluate their geometric and mechanical effects on the marginal bone. Results: Among the three thread shapes with the same pitch, the contact area of the square thread was the highest. Among all implant models, it was found that the site with the greatest stress in the surrounding jaw bone was consistently concentrated at the root radii of the first thread. The maximal stress of the square thread was the least. For the same thread shape and taper, a finer pitch resulted in a remarkable increase in the contact area and a decrease in the peak stress. The contact areas and peak stresses of the conical and cylindrical implants were nearly equal. Conclusion: Taking wall thickness and stress concentrations into consideration, the square thread with a 0.60-mm pitch possessed the optimal contact area and stress values compared to the others.

Patients undergoing kidney transplantation have a poor response to vaccination and a higher risk of disease progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of vaccine doses and antibody titer tests against the mutant variant in these patients remains unclear. We retrospectively analyzed the risk of SARS-CoV-2 infection in a single medical center according to vaccine doses and immune responses before the outbreak. Among 622 kidney transplant patients, there were 77 patients without vaccination, 26 with one dose, 74 with two doses, 357 with three, and 88 with four doses. The vaccination status and infection rate proportion were similar to the general population. Patients undergoing more than three vaccinations had a lower risk of infection (odds ratio = 0.6527, 95% CI = 0.4324–0.9937) and hospitalization (odds ratio = 0.3161, 95% CI = 0.1311–0.7464). Antibody and cellular responses were measured in 181 patients after vaccination. Anti-spike protein antibody titer of more than 1,689.3 BAU/mL is protective against SARS-CoV-2 infection (odds ratio = 0.4136, 95% CI = 0.1800–0.9043). A cellular response by interferon-γ release assay was not correlated with the disease (odds ratio = 1.001, 95% CI = 0.9995–1.002). In conclusion, despite mutant strain, more than three doses of the first-generation vaccine and high antibody titers provided better protection against the omicron variant for a kidney transplant recipient. [ABSTRACT FROM AUTHOR]

An efficient and mild fluorination of vinyl azides for the synthesis of α-fluoroketones is described. The mechanistic studies indicated that a single-electron transfer (SET) and a subsequent fluorine atom transfer process could be involved in the reaction. [ABSTRACT FROM AUTHOR]

A metal-free efficient synthesis of olefins via microwave-assisted direct decarboxylative elimination of arylacetic acids is described. This reaction, using commercially available reagent PIFA as oxidant, readily provides a variety of desired products in moderate to good yields. [ABSTRACT FROM AUTHOR]