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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 Diabetic wounds, characterized by complex pathogenesis and high infection rates, pose significant challenges in treatment due to prolonged recovery times and high recurrence rates, often leading to severe complications such as amputation and death. Traditional dry dressing treatments fail to address the unique microenvironment of diabetic wounds and tend to cause secondary damage due to frequent replacement. In this study, an electronic‐embedding, drug‐loading hydrogel bioelectronics is reported for accelerating diabetic wound healing using a combination of programmable pharmaceutical and electrostimulative approaches. Encapsulated in stretchable and biocompatible materials, this device is capable of multiple drug refilling and accelerated drug release modulated by on‐board electronics. In vivo experiments on diabetic model rats confirm the device's effectiveness in promoting wound healing. This innovative approach implies the potential for improving diabetic wound management using a combination of physical, material, and pharmaceutical interventions.

Abstract Introduction Prior studies suggested that neuromuscular factors might be involved in the pathogenesis of adolescent idiopathic scoliosis (AIS). The neuromuscular junction (NMJ) is the important pivot where the nervous system interacts with muscle fibers, but it has not been well characterized in the paraspinal muscles of AIS. This study aims to perform the quantitative morphological analysis of NMJs from paraspinal muscles of AIS. Methods AIS patients who received surgery in our center were prospectively enrolled. Meanwhile, age‐matched congenital scoliosis (CS) and non‐scoliosis patients were also included as controls. Fresh samples of paraspinal muscles were harvested intraoperatively. NMJs were immunolabeled using different antibodies to reveal pre‐synaptic neuronal architecture and post‐synaptic motor endplates. A confocal microscope was used to acquire z‐stack projections of NMJs images. Then, NMJs images were analyzed on maximum intensity projections using ImageJ software. The morphology of NMJs was quantitatively measured by a standardized ‘NMJ‐morph’ workflow. A total of 21 variables were measured and compared between different groups. Results A total of 15 AIS patients, 10 CS patients and 5 normal controls were enrolled initially. For AIS group, NMJs in the convex side of paraspinal muscles demonstrated obviously decreased overlap when compared with the concave side (34.27% ± 8.09% vs. 48.11% ± 10.31%, p = 0.0036). However, no variables showed statistical difference between both sides of paraspinal muscles in CS patients. In contrast with non‐scoliosis controls, both sides of paraspinal muscles in AIS patients demonstrated significantly smaller muscle bundle diameters. Conclusions This study first elucidated the morphological features of NMJs from paraspinal muscles of AIS patients. The NMJs in the convex side showed smaller overlap for AIS patients, but no difference was found in CS. This proved further evidence that neuromuscular factors might contribute to the mechanisms of AIS and could be considered as a novel potential therapeutic target for the treatment of progressive AIS.

Asthma is a widespread public health concern, with an increasing incidence. Despite the implementation of current treatment strategies, asthma control, particularly for severe cases, remains suboptimal. Recent research has revealed the encouraging prospects of extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) as a viable therapeutic option for alleviating asthma symptoms. Therefore, the present review aims to provide an overview of the current progress and the therapeutic mechanisms of using MSC-derived EVs (MSC-EVs) for asthma treatment. Additionally, different administration approaches for EVs and their impacts on biodistribution and the curative outcomes of EVs are summarized. Notably, the potential benefits of nebulized inhalation of MSC-EVs are addressed. Also, the possibilities and challenges of using MSC-EVs for asthma treatment in clinics are highlighted. Overall, this review is intended to give new insight into the utilization of MSC-EVs as a potential biological drug for asthma treatment.

The strength and plasticity trade-off in metal materials can be effectively addressed by Eutectic High-Entropy Alloys (EHEAs) through the realization of heterogeneous biphase layered structures at both micrometer and nanometer scales. In this work, a series of (CoCrFeNi)88NbxW(12-x) EHEAs were prepared, and the effects of the synergistic of Nb and W elements on the microstructure and mechanical properties of CoCrFeNi High-Entropy Alloys (HEAs) were investigated. With the increase of Nb content and the decrease of W content, the microstructure of the alloy underwent three changes, from Face Center Cubic (FCC) + μ biphase to FCC + μ + Laves triple phase, and finally to FCC + Laves biphase. The strength of the alloy increases, but the compression rate decreases. Among these alloys, (CoCrFeNi)88Nb10W2 alloy exhibits exceptional mechanical properties. The synergistic effect of precipitation strengthening and grain boundary strengthening makes the yield strength, fracture strength, and plastic strain of the alloy are 1568 MPa, 2516 MPa, and 32 % respectively. In addition, in the CoCrFeNi HEAs, the weighted average atomic radius ratio (rm‾/rQ) is used to further precise the phase selection law of Laves phase and μ phase. When rm‾/rQ < 1.112, HEAs forms the μ phase, when 1.112 ≤ rm‾/rQ ≤ 1.14, HEAs forms the Laves + μ biphase, when rm‾/rQ > 1.14, HEAs forms the Laves phase. The results can provide a basis for synergistic strengthening and phase selection of CoCrFeNi HEAs.

Morchella, a highly valued medicinal and edible mushrooms, is experiencing an increasing demand; however, its cultivation is significantly influenced by climatic conditions and soil characteristics. Consequently, elucidating the mechanisms underlying Morchella mycelium’s response to temperature stress holds substantial importance for enhancing Morchella cultivation practices. In this study, we used Morchella sextelata as the research object and employed integrated transcriptomic and metabolomic analyses to evaluate the effects of cultivation temperatures set at 33 °C, 20 °C, and 4 °C on the vegetative mycelium of Morchella. Through these comprehensive analyses, we identified 2998 differentially expressed genes alongside 678 differentially accumulated metabolites. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA), we constructed a co-expression network that revealed hub genes and metabolites within each module. Furthermore, through KEGG pathway analysis, we pinpointed significant metabolic pathways responsive to temperature stress—particularly those involved in purine metabolism, RNA degradation, two-component systems, ABC transporters, and pyruvate metabolism. Overall findings indicated that elevated temperatures exerted a more pronounced effect on M. sextelata mycelium compared to lower temperatures. These insights enhance our comprehension of the adaptive mechanisms of M. sextelata to thermal variations while providing valuable references for optimizing environmental temperature regulation in their cultivation as well as offering clues for selecting varieties capable of thriving under diverse thermal conditions.

Long non-coding RNAs (lncRNAs) are crucial in regulating secondary metabolite production in plants, but their role in artemisinin (ART) biosynthesis, a key anti-malarial compound from Artemisia annua, remains unclear. Here, by investigating high-artemisinin-producing (HAP) and lowartemisinin-producing (LAP) genotypes, we found that the final artemisinin content in A. annua is influenced by the quantity of the precursor compounds. We report on RNA deep sequencing in HAP and LAP genotypes. Based on the application of a stringent pipeline, 1419 novel lncRNAs were identified. Moreover, we identified 256 differentially expressed lncRNAs between HAP and LAP. We then established correlations between lncRNAs and artemisinin biosynthesis genes in order to identify a molecular framework for the differential expression of the pathway between the two genotypes. Three potential lncRNAs (MSTRG.33718.2, MSTRG.30396.1 and MSTRG.2697.4) linked to the key artemisinin biosynthetic genes (ADS: Amorpha-4,11-diene synthase, DXS: 1-deoxy-D-xylulose-5-phosphate synthase, and HMGS: 3-hydroxyl-3-methyglutaryl CoA synthase) were detected. Importantly, we observed that up-regulation of these lncRNAs positively modulates the target artemisinin biosynthetic genes, potentially leading to high artemisinin biosynthesis in HAP. In contrast, BAS (beta-amyrin synthase), which is involved in the artemisinin competing pathway, was strongly down-regulated in HAP compared to LAP, in line with the expression pattern of the linked lncRNA MSTRG.30396.1. By identifying and characterizing lncRNAs that are potentially linked to the regulation of key biosynthetic genes, this work provides new insights into the complex regulatory networks governing artemisinin production in A. annua. Such findings could pave the way for innovative approaches in metabolic engineering, potentially enhancing artemisinin yields and addressing challenges in sustainable production.

The Tibetan Plateau, characterized by complicated geological structures, is sensitive to climate change and human activities. The vulnerable environmental balance of the Tibetan Plateau has witnessed substantial alterations, emphasizing the urgency to comprehend and protect its ecosystem quality. In this study, we aim to quantify the ecosystem quality of the Tibetan Plateau, portray its spatiotemporal dynamics, and analyze the spatial heterogeneity of climatic and anthropogenic influences. We employed the entropy weight method (EWM) to construct a comprehensive index, termed the Ecosystem Quality Comprehensive Assessment Index (EQCAI). The historical spatiotemporal patterns and trends of EQCAI were subsequently identified. Our results revealed a gradient of decreasing ecosystem quality from the southeast to the northwest of the Tibetan Plateau, while the mitigation of ecosystem quality degradation displayed an improving trend from the southwest to the northeast. We further detected the spatial heterogeneity of factors influencing changes in ecosystem quality through the multiscale geographically weighted regression (MGWR) method. Precipitation emerged as the primary positive factor, exerting a profound influence on the ecosystem quality of the southeastern Tibetan Plateau. Conversely, evapotranspiration, elevation, and human activities negatively affected the western Tibetan Plateau. This study proposes targeted conservation efforts for forestry regions with high ecosystem quality in the southeastern Tibetan Plateau. Additionally, we suggest that the positive impact of human activities on the ecosystem quality of the Tibetan Plateau should be further strengthened. Our findings contribute valuable insights for informed decision-making in the sustainable management and preservation of the Tibetan Plateau's fragile ecosystem.

IntroductionThoracolumbosacral orthosis (TLSO) is the most commonly used type of brace for the conservative treatment of adolescent idiopathic scoliosis (AIS). Although lumbosacral orthosis (LSO) is designed to correct single thoracolumbar or lumbar (TL/L) curves, its effectiveness remains underexplored. This novel article aims to compare the effectiveness of LSO with TLSO in treating AIS with main TL/L curves.MethodsThis prospective controlled cohort study enrolled patients with AIS with main TL/L curves and minor thoracic curves who were treated with either TLSO or LSO. Demographic and radiographic data were compared between the two groups. Treatment outcomes were also assessed. Risk factors for minor curve progression were identified, and a cut-off value was determined within the LSO group.ResultsOverall, 82 patients were recruited, including 44 in the TLSO group and 38 in the LSO group. The initial TL/L curves showed no difference between both groups. However, the baseline thoracic curves were significantly larger in the TLSO group compared to the LSO group (25.98° ± 7.47° vs. 18.71° ± 5.95°, P

Chlamydia trachomatis is responsible for infections in various mucosal tissues, including the eyes, urogenital, respiratory, and gastrointestinal tracts. Chronic infections can result in severe consequences such as blindness, ectopic pregnancy, and infertility. The underlying mechanisms leading to these diseases involve sustained inflammatory responses, yet thorough comprehension of the underlying mechanisms remains elusive. Chlamydial biologists employ in multiple methods, integrating biochemistry, cell biology, and genetic tools to identify bacterial factors crucial for host cell interactions. While numerous animal models exist to study chlamydial pathogenesis and assess vaccine efficacy, selecting appropriate models for biologically and clinically relevant insights remains a challenge. Genital infection models in animals have been pivotal in unraveling host-microbe dynamics, identifying potential chlamydial virulence factors influencing genital pathogenicity. However, the transferability of this knowledge to human pathogenic mechanisms remains uncertain. Many putative virulence factors lack assessment in optimal animal tissue microenvironments, despite the diverse chlamydial infection models available. Given the propensity of genital Chlamydia to spread to the gastrointestinal tract, investigations into the pathogenicity and immunological impact of gut Chlamydia become imperative. Notably, the gut emerges as a promising site for both chlamydial infection vaccination and pathogenesis. This review elucidates the pathogenesis of Chlamydia infections and delineates unique features of prevalent animal model systems. The primary focus of this review is to consolidate and summarize current animal models utilized in Chlamydia researches, presenting findings, discussions on their contributions, and suggesting potential directions for further studies.

In this paper, we propose an improved adaptive frequency sweep strategy based on the asymptotic waveform evaluation (AWE) technique for simulating broadband antennas across a wide frequency range. Our approach maintains high accuracy compared to traditional frequency sweep methods, as demonstrated through simulation results of several commonly used broadband antennas. A novel error function is introduced specifically designed for broadband antenna simulation, which effectively improves the adaptive frequency sweep process. By analyzing the relationship between target error and computational time, we determine the optimal balance zone between efficiency and accuracy. Our findings provide valuable insights for efficient and accurate simulation of broadband antennas.

Background: A hospital-based case-control study was carried out to elucidate the association of Matrix metalloproteinase-2 (MMP-2) gene candidate polymorphisms with the susceptibility to Alzheimer’s disease (AD) in the Chinese Han population. Methods: A total of 200 AD cases and an equal number of healthy controls were recruited to undergo genotyping of specific loci within the MMP-2 gene loci (rs243866, rs2285053, rs243865). Logistic regression analysis was applied to examine the association of the genotypes and alleles of MMP-2 gene polymorphisms with AD after adjusting clinical confounding factors. Results: Within AD group, a high proportion of rs243866 genotype carriers were found, and the difference remained significant despite adjusting for other clinical indicators. Among individuals with the rs243866 AA genotype and rs243865 TT genotype, the onset age of AD occurred at a younger age. Early-onset AD risk in rs243866 AA genotype carriers was 6.528 times higher than those in GG genotype carriers, and individuals with rs243865 TT genotype faced a 4.048-fold increased risk compared to those with CC genotype. Conclusions: MMP-2 gene rs243866 and rs243865 polymorphisms were closely associated with the onset age of AD. The presence of rs243866 AA genotype emerged as a crucial predictor of AD risk.

The glyoxalase pathway is the primary detoxification mechanism for methylglyoxal (MG), a ubiquitous toxic metabolite that disrupts redox homeostasis. In the glyoxalase pathway, glyoxalase II (GlyII) can completely detoxify MG. Increasing the activity of the glyoxalase system can enhance the resistance of plants or organisms to abiotic stress, but the relevant mechanism remains largely unknown. In this study, we investigated the physiological functions of GlyII genes (sll1019 and slr1259) in Synechocystis sp. PCC 6803 under MG or ethanol stress based on transcriptome and metabolome data. High-performance liquid chromatography (HPLC) results showed that proteins Sll1019 and Slr1259 had GlyII activity. Under stress conditions, sll1019 and slr1259 protected the strain against oxidative stress by enhancing the activity of the glyoxalase pathway and raising the contents of antioxidants such as glutathione and superoxide dismutase. In the photosynthetic system, sll1019 and slr1259 indirectly affected the light energy absorption by strains, synthesis of photosynthetic pigments, and activities of photosystem I and photosystem II, which was crucial for the growth of the strain under stress conditions. In addition, sll1019 and slr1259 enhanced the tolerance of strain to oxidative stress by indirectly regulating metabolic networks, including ensuring energy acquisition, NADH and NADPH production, and phosphate and nitrate transport. This study reveals the mechanism by which sll1019 and slr1259 improve oxidative stress tolerance of strains by glyoxalase pathway. Our findings provide theoretical basis for breeding, seedling, and field production of abiotic stress tolerance-enhanced variety. IMPORTANCE The glyoxalase system is present in most organisms, and it is the primary pathway for eliminating the toxic metabolite methylglyoxal. Increasing the activity of the glyoxalase system can enhance plant resistance to environmental stress, but the relevant mechanism is poorly understood. This study revealed the physiological functions of glyoxalase II genes sll1019 and slr1259 in Synechocystis sp. PCC 6803 under abiotic stress conditions and their regulatory effects on oxidative stress tolerance of strains. Under stress conditions, sll1019 and slr1259 enhanced the activity of the glyoxalase pathway and the antioxidant system, maintained photosynthesis, ensured energy acquisition, NADH and NADPH production, and phosphate and nitrate transport, thereby protecting the strain against oxidative stress. This study lays a foundation for further deciphering the mechanism by which the glyoxalase system enhances the tolerance of cells to abiotic stress, providing important information for breeding, seedling, and selection of plants with strong stress resistance. [ABSTRACT FROM AUTHOR]