Succinylation modification provides new insights for the treatment of immunocompromised individuals with drug-resistant Aspergillus fumigatus infection

Invasive Aspergillus fumigatus infection poses a serious threat to global human health, especially to immunocompromised individuals. Currently, triazole drugs are the most commonly used antifungals for aspergillosis. However, owing to the emergence of drug-resistant strains, the effect of triazole drugs is greatly restricted, resulting in a mortality rate as high as 80%. Succinylation, a novel post-translational modification, is attracting increasing interest, although its biological function in triazole resistance remains unclear. In this study, we initiated the screening of lysine succinylation in A. fumigatus. We discovered that some of the succinylation sites differed significantly among strains with unequal itraconazole (ITR) resistance. Bioinformatics analysis showed that the succinylated proteins are involved in a broad range of cellular functions with diverse subcellular localizations, the most notable of which is cell metabolism. Further antifungal sensitivity tests confirmed the synergistic fungicidal effects of dessuccinylase inhibitor nicotinamide (NAM) on ITR-resistant A. fumigatus. In vivo experiments revealed that treatment with NAM alone or in combination with ITR significantly increased the survival of neutropenic mice infected with A. fumigatus. In vitro experiments showed that NAM enhanced the killing effect of THP-1 macrophages on A. fumigatus conidia. Our results suggest that lysine succinylation plays an indispensable role in ITR resistance of A. fumigatus. Dessuccinylase inhibitor NAM alone or in combination with ITR exerted good effects against A. fumigatus infection in terms of synergistic fungicidal effect and enhancing macrophage killing effect. These results provide mechanistic insights that will aid in the treatment of ITR-resistant fungal infections

Low-temperature microstructural studies on superconducting CaFe2As2.

Undoped CaFe2As2 (Ca122) can be stabilized in two slightly different non-superconducting tetragonal phases, PI and PII, through thermal treatments. Upon proper annealing, superconductivity with a Tc up to 25 K emerges in the samples with an admixture of PI and PII phases. Systematic low-temperature X-ray diffraction studies were conducted on undoped Ca122 samples annealed at 350 °C over different time periods. In addition to the diffraction peaks associated with the single-phase aggregation of PI and PII, a broad intermediate peak that shifts with annealing time was observed in the superconducting samples only. Our simulation of phase distribution suggests that the extra peak is associated with the admixture of PI and PII on the nanometer scale. High-resolution transmission electron microscopy confirms the existence of these nano-scale phase admixtures in the superconducting samples. These experimental results and simulation analyses lend further support for our conclusion that interfacial inducement is the most reasonable explanation for the emergence of superconductivity in undoped Ca122 single crystals

Polyhedral Carbon Anchored on Carbon Nanosheet with Abundant Atomic Fe-Nx Moieties for Oxygen Reduction

Carbon-based single-atom iron electrocatalysts with nitrogen coordination (CSAIN) have recently shown enormous promise to replace the costly Pt for boosting the cathodic oxygen reduction reaction (ORR) in fuel cells. However, there remains a great challenge to achieve highly efficient CSAIN catalysts for the ORR in acidic electrolytes. Herein, a novel CSAIN catalyst is synthesized by pyrolyzing a precursor mixture consisting of metal–organic framework and conductive polymer hybrid. After pyrolysis at a high temperature, the CSAIN with a structure of carbon nanosheet supported polyhedral carbon is achieved, where the unique structure endows CSAIN with expediting electron transfer and mass transport, as well as largely exposed surface to host atomically dispersed iron active sites. As a result, the optimal CSAIN catalyst shows a high ORR activity with its half-wave potential of 0.77 V (vs RHE) and a Tafel slope of 74.1 mV dec–1, which are comparable to that of commercial Pt/C catalyst (0.80 V and 81.9 mV dec–1)

Conductive polymer based hydrogels and their application in wearable sensors: a review

Hydrogels have been attracting increasing attention in wearable electronics, due to their intrinsic biomimetic features, highly tunable chemical-physical properties (mechanical, electrical, etc), and excellent biocompatibility. Among many proposed varieties, conductive polymer-based hydrogels (CPHs) have emerged as a promising candidate for future wearable sensor designs, with a capability of realizing desired features using different tuning strategies ranging from molecular design (with a low lengthscale of 10-10 m) to micro-structural configuration (up to a lengthscale of 10-2 m). However, considerable challenges remain to be overcome, such as the limited strain sensing range due to the mechanical strength, the signal loss/instability caused by swelling/deswelling, the significant hysteresis of sensing signal, the de-hydration induced malfunctions, the surface/interfacial failure during manufacturing/processing, etc. This review aims to offer a targeted scan of recent advancements in CPH based wearable sensor technology, from the establishment of dedicated structure-property relationships in the lab to the advanced manufacturing routes for potential scale-up production. The application of CPHs in wearable sensors is also explored, with suggested new research avenues and prospects for CPHs in the future also included.Abstract text goes here

New innovations in pavement materials and engineering: A review on pavement engineering research 2021

Sustainable and resilient pavement infrastructure is critical for current economic and environmental challenges. In the past 10 years, the pavement infrastructure strongly supports the rapid development of the global social economy. New theories, new methods, new technologies and new materials related to pavement engineering are emerging. Deterioration of pavement infrastructure is a typical multi-physics problem. Because of actual coupled behaviors of traffic and environmental conditions, predictions of pavement service life become more and more complicated and require a deep knowledge of pavement material analysis. In order to summarize the current and determine the future research of pavement engineering, Journal of Traffic and Transportation Engineering (English Edition) has launched a review paper on the topic of “New innovations in pavement materials and engineering: A review on pavement engineering research 2021”. Based on the joint-effort of 43 scholars from 24 well-known universities in highway engineering, this review paper systematically analyzes the research status and future development direction of 5 major fields of pavement engineering in the world. The content includes asphalt binder performance and modeling, mixture performance and modeling of pavement materials, multi-scale mechanics, green and sustainable pavement, and intelligent pavement. Overall, this review paper is able to provide references and insights for researchers and engineers in the field of pavement engineering

Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb/c mice

There has been lack of the uniform standard for establishment of animal immunodepressive models induced by cyclophosphamide (CTX), and the information about the immunosuppressive effect of CTX on peripheral blood lymphocyte subsets in rodents. Here we describe a CTX-induced mouse model and try to establish a feasible immunosuppressive model for studying the fungal pathogenicity. Balb/c mice received two intraperitoneal injections of different CTX doses (50–200 mg/kg) at 2-day intervals. Peripheral whole blood collected at different time-points before and after CTX injection was used to detect white blood cells (WBCs), lymphocytes and their subsets by automated hematology analyzer and flow cytometry, respectively. WBCs and lymphocytes in all groups except CTX50 (50 mg/kg CTX) group commenced to decrease in a dose-dependent manner on day 1, reached the nadir on day 4, rebounded on day 10, and declined again on day 17 after CTX treatment. Low dose (50 mg/kg) CTX produced no obvious change of percentage of CD3+, CD4+ and CD8+ T cells and CD19+ cells, but high doses (100 or 150 mg/kg) yielded a significant decrease of CD3+ and CD4+ cells on day 4 and CD19+ cells on day 10, and increase of CD8+ cells on day 4. The CD4+/CD8+ ratio decreased on day 4, followed by a rebound thereafter when treated with 3 different doses of CTX. The results indicate that two intraperitoneal injections of CTX at 150 mg/kg at 2-day intervals may establish good immunosuppressive models of Balb/c mice for studying the fungal pathogenicity