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We herein reported a sustainable synthesis of 3,3-disubstituted oxindoles via a Michael-type reaction based on the CuBr-catalysed capture of carboxylic oxonium ylides with isatylidene malononitrile. The reaction is characterized by a high atom economy and low economic constraints. The catalyst CuBr could be conveniently recyclized. The products of the reaction were found to be inhibitory against Na ion channels. We expect the reaction to shed the light on synthesis of biologically interesting molecules directed by principles of green chemistry.

Abstract While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis.

Abstract Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight in rice. Polyhydroxyalkanoates (PHAs) consitute a diverse group of biopolyesters synthesized by bacteria under nutrient-limited conditions. The phaC gene is important for PHA polymerization. We investigated the effects of phaC gene mutagensis in Xoo strain PXO99A. The phaC gene knock-out mutant exhibited reduced swarming ability relative to that of the wild-type. Under conditions where glucose was the sole sugar source, extracellular polysaccharide (EPS) production by ΔphaC declined by 44.8%. ΔphaC showed weak hypersensitive response (HR) induction in the leaves of non-host Nicotiana tabacum, concomitant with downregulation of hpa1 gene expression. When inoculated in rice leaves by the leaf-clipping method, ΔphaC displayed reduced virulence in terms of lesion length compared with the wild-type strain. The complemented strain showed no significant difference from the wild-type strain, suggesting that the deletion of phaC in Xoo induces significant alterations in various physiological and biological processes. These include bacterial swarming ability, EPS production, transcription of hrp genes, and glucose metabolism. These changes are intricately linked to the energy utilization and virulence of Xoo during plant infection. These findings revealed involvement of phaC in Xoo is in the maintaining carbon metabolism by functioning in the PHA metabolic pathway.

Abstract The maintenance of hematopoietic stem cell (HSC) functional integrity is essential for effective hematopoietic regeneration when suffering from injuries. Studies have shown that the innate immune pathways play crucial roles in the stress response of HSCs, whereas how to precisely modulate these pathways is not well characterized. Here, we identify the E3 ubiquitin ligase tripartite motif-containing 47 (Trim47) as a negative regulator of the mitochondrial antiviral-signaling protein (MAVS)-mediated innate immune pathway in HSCs. We find that Trim47 is predominantly enriched in HSCs, and its deficiency impairs the function and survival of HSCs after exposure to 5-flurouracil (5-FU) and irradiation (IR). Mechanistically, Trim47 impedes the excessive activation of the innate immune signaling and inflammatory response via K48-linked ubiquitination and degradation of MAVS. Collectively, our findings demonstrate a role of Trim47 in preventing stress-induced hematopoietic failure and thus provide a promising avenue for treatment of related diseases in the clinic.

In the study of coal powder reburning technology, combining the coal powder delivery via recirculating flue gas and natural gas conditioning was proposed. The purpose of this approach is to enhance the reduction capability of coal powder reburning, thereby reducing the emission of nitrogen oxides from coal-fired boilers. The main objective of the research is to explore how to utilize the highly reactive components in natural gas to create a more favorable environment for coal powder to reduce nitrogen oxides. To achieve this, a detailed investigation of the entire process of natural gas conditioning was conducted using a multi-reaction control section with a flow reactor experimental system simulating actual coal-fired boiler conditions. The results revealed that the abundant reduction substances generated during natural gas conditioning, such as CO*, OH*, H, and CHi, optimized the physical and chemical structure of coal char, thereby enhancing its ability to reduce nitrogen oxides. Compared with traditional coal powder delivery via recirculating flue gas, the addition of natural gas conditioning significantly increased the efficiency of nitrogen oxide reduction by approximately 12.23%. Through experimental investigation and data analysis, the significant impact of natural gas conditioning technology on coal powder reburning was elucidated, and the specific parameter requirements for engineering applications were proposed. From an engineering perspective, the precise control of the excess air ratio, residence time, and fuel ratio in the reburning zone is essential to achieve a high-efficiency nitrogen oxide reduction while ensuring a complete coal powder combustion and economic feasibility. Overall, adopting natural gas conditioning technology can not only guarantee ultra-low nitrogen oxide emissions but also minimize the use of reactive gases, thereby enhancing the economic efficiency of system operation. This flexible use of natural gas technology has demonstrated some promising results in laboratory conditions and offers feasible solutions for engineering practice, ensuring the economic efficiency of system operation.

Abstract α-Actinins play crucial roles in cytoskeletal mechanobiology by acting as force-bearing structural modules that orchestrate and sustain the cytoskeletal framework, serving as pivotal hubs for diverse mechanosensing proteins. The mechanical stability of α-actinin dimer, a determinant of its functional state, remains largely unexplored. Here, we directly quantify the force-dependent lifetimes of homo- and hetero-dimers of human α-actinins, revealing an ultra-high mechanical stability of the dimers associated with > 100 seconds lifetime within 40 pN forces under shear-stretching geometry. Intriguingly, we uncover that the strong dimer stability is arisen from much weaker sub-domain pair interactions, suggesting the existence of distinct dimerized functional states of the dimer, spanning a spectrum of mechanical stability, with the spectrin repeats (SRs) in folded or unfolded conformation. In essence, our study supports a potent mechanism for building strength in biomolecular dimers through weak, multiple sub-domain interactions, and illuminates multifaceted roles of α-actinin dimers in cytoskeletal mechanics and mechanotransduction.

Abstract For superconducting quantum processors, microwave signals are delivered to each qubit from room-temperature electronics to the cryogenic environment through coaxial cables. Limited by the heat load of cabling and the massive cost of electronics, such an architecture is not viable for millions of qubits required for fault-tolerant quantum computing. Monolithic integration of the control electronics and the qubits provides a promising solution, which, however, requires a coherent cryogenic microwave pulse generator that is compatible with superconducting quantum circuits. Here, we report such a signal source driven by digital-like signals, generating pulsed microwave emission with well-controlled phase, intensity, and frequency directly at millikelvin temperatures. We showcase high-fidelity readout of superconducting qubits with the microwave pulse generator. The device demonstrated here has a small footprint, negligible heat load, great flexibility to operate, and is fully compatible with today’s superconducting quantum circuits, thus providing an enabling technology for large-scale superconducting quantum computers.

The underwater 10CrNi3MoV high-strength low-alloy steel thin-walled part with forming quality up to in-air laser deposition quality was successfully manufactured for the first time. The influencing mechanisms of complicated thermal history and water environment on microstructure evolution and mechanical properties of thin-walled part were researched. Due to austenitization and interlocking effect, the microstructure in the bottom, middle and top (below the 56th layer) areas of underwater sample and the middle area of in-air sample were composed of fine grain ferrite and granular bainite. With the increase of building height, the heat accumulation effect of underwater sample enhanced, resulting in small grain size (GS), high dislocation density, strong solution strengthening effect and low maximum texture strength at the bottom area, while the high proportion of high-angle grain boundaries (HAGBs) at the top area. These resulted in the greatest tensile strength (714 MPa) and microhardness (232 HV) at the bottom area and the highest elongation (11%) at the top area. Due to the cooling effect of water environment, the proportion of HAGBs reduced and there were oxides in fracture. As a result, the horizontal elongation of underwater sample was about 90.9% of in-air sample. Additionally, the GS reduced, and the dislocation density and solution strengthening effect increased, so the microhardness of underwater sample was slightly higher than that of in-air sample. However, due to some microscopic defects, the horizontal and vertical tensile strength of underwater sample were about 97.6% and 90.7% of in-air sample.

Abstract Background Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of MSCs has exhibited superior therapeutic efficacy on IBD than intravenous injection. Nevertheless, the precise in vivo distribution of MSCs and their biological consequences following intraperitoneal injection remain inadequately understood. Additional studies are required to explore the correlation between MSCs distribution and their biological effects. Methods First, the distribution of human umbilical cord MSCs (hUC-MSCs) and the numbers of Treg and Th17 cells in mesenteric lymph nodes (MLNs) were analyzed after intraperitoneal injection of hUC-MSCs. Subsequently, the investigation focused on the levels of transforming growth factor beta1 (TGF-β1), a key cytokine to the biology of both Treg and Th17 cells, in tissues of mice with colitis, particularly in MLNs. The study also delved into the impact of hUC-MSCs therapy on Treg cell counts in MLNs, as well as the consequence of TGFB1 knockdown hUC-MSCs on the differentiation of Treg cells and the treatment of IBD. Results The therapeutic effectiveness of intraperitoneally administered hUC-MSCs in the treatment of colitis was found to be significant, which was closely related to their quick migration to MLNs and secretion of TGF-β1. The abundance of hUC-MSCs in MLNs of colitis mice is much higher than that in other organs even the inflamed sites of colon. Intraperitoneal injection of hUC-MSCs led to a significant increase in the number of Treg cells and a decrease in Th17 cells especially in MLNs. Furthermore, the concentration of TGF-β1, the key cytokine for Treg differentiation, were also found to be significantly elevated in MLNs after hUC-MSCs treatment. Knockdown of TGFB1 in hUC-MSCs resulted in a noticeable reduction of Treg cells in MLNs and the eventually failure of hUC-MSCs therapy in colitis. Conclusions MLNs may be a critical site for the regulatory effect of hUC-MSCs on Treg/Th17 cells and the therapeutic effect on colitis. TGF-β1 derived from hUC-MSCs promotes local Treg differentiation in MLNs. This study will provide new ideas for the development of MSC-based therapeutic strategies in IBD patients.