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Based on the “unidirectional break-up and convergence” geodynamic model, this study investigates the impact of the evolution of the Tethyan domain on the formation of petroleum systems in the Sichuan super basin and explores the enrichment pattern of natural gas. The results show that, firstly, the Sichuan Basin and its surrounding areas have experienced two unidirectional rifting-aggregation cycles triggered by the Proto-Tethys Ocean and the Paleo-Tethys Ocean during the Neoproterozoic to Triassic. During Jurassic–Cenozoic, the Sichuan Basin is incorporated in the circum-Tibetan plateau basin-mountain coupled tectonic domain system. The episodic tectonic movements within the plate control the sedimentary infill styles. Second, the evolution of the Tethyan domain, paleoclimatic environment and major geological events controlled the formation and distribution of high-quality source rocks within the basin. The rift valley and intracratonic rift, passive continental margin slope, and intracratonic sags are favorable areas for the development of source rocks. Third, the evolution of the Tethyan domain, supercontinent cycles, global sea level changes, and tectono-climatic events controlled the distribution of carbonate platform and reservoir-caprock combinations. The cratonic platform margins and sub-platform internal high terrains are key areas for finding carbonate high-energy facies belts. Syndepositional paleo-uplifts and surrounding slopes, regional unconformities, and later faults zone are areas where large-scale carbonate reservoirs are distributed. The regional evaporite or shale caprock are beneficial for the large-scale preservation of oil and gas in the basin. Fourth, the spatio-temporal matching relationship of reservoir forming factors influenced by the early tectonic-sedimentary evolution pattern and the degree of later tectonic modification is the key to oil and gas enrichment. Future oil and gas exploration should focus on potential gas systems during the Sinian rift period, Cambrian pre-salt gas systems in the eastern and southern Sichuan, as well as whole oil and gas systems of Permian and Triassic.

Abstract There is cumulative evidence that lipid metabolism plays a key role in the pathogenesis of various neurodegenerative disorders including Alzheimer’s disease (AD). Visualising lipid content in a non-destructive label-free manner can aid in elucidating the AD phenotypes towards a better understanding of the disease. In this study, we combined multiple optical molecular-specific methods, Fourier transform infrared (FTIR) spectroscopic imaging, synchrotron radiation-infrared (SR-IR) microscopy, Raman and stimulated Raman scattering (SRS) microscopy, and optical-photothermal infrared (O-PTIR) microscopy with multivariate data analysis, to investigate the biochemistry of brain hippocampus in situ using a mouse model of tauopathy (rTg4510). We observed a significant difference in the morphology and lipid content between transgenic (TG) and wild type (WT) samples. Immunohistochemical staining revealed some degree of microglia co-localisation with elevated lipids in the brain. These results provide new evidence of tauopathy-related dysfunction in a preclinical study at a subcellular level.

The microstructure, texture, and mechanical properties of as-extruded and cold-rolled Mg–8Li–3Al–2Zn-1Gd-0.2Zr (LAZ832-1Gd-0.2Zr) alloys were investigated with the aim of strengthening the alloy by combining hot extrusion and cold rolling. Cold rolling does not change the phase composition of as-extruded LAZ832-1Gd-0.2Zr alloy, but introduces a larger number of dislocations and twins into alloy matrix. Cold rolling leads to the weakening of the original {0001} basal and {112‾0}-{011‾0} prismatic textures in α-Mg matrix, as well as the α and γ fiber textures in β-Li matrix. But new slip systems that are favorable for cold rolling are activated, resulting in the formation of {033‾8} pyramidal and new prismatic ({112‾0}⟨101‾4⟩ and {101‾0}⟨21‾1‾10⟩) texture components. Cold rolling further strengthens LAZ832-1Gd-0.2Zr alloy on the basis of hot extrusion, mainly through work hardening effect caused by introducing a large number of dislocations into α-Mg matrix. When the rolling reduction is 45%, the yield strength and tensile strength of LAZ832-1Gd-0.2Zr alloy are increased to 269.8 ± 4.0 and 308.6 ± 4.1 MPa, respectively, and the elongation is higher than 15%.

Abstract Dysfunction of pancreatic δ cells contributes to the etiology of diabetes. Despite their important role, human δ cells are scarce, limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. Here, we demonstrate that fibroblast growth factor (FGF) 7 promotes pancreatic endoderm/progenitor differentiation, whereas FGF2 biases cells towards the pancreatic δ-cell lineage via FGF receptor 1. We develop a differentiation method to generate δ cells from human stem cells by combining FGF2 with FGF7, which synergistically directs pancreatic lineage differentiation and modulates the expression of transcription factors and SST activators during endoderm/endocrine precursor induction. These δ cells display mature RNA profiles and fine secretory granules, secrete somatostatin in response to various stimuli, and suppress insulin secretion from in vitro co-cultured β cells and mouse β cells upon transplantation. The generation of human pancreatic δ cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation studies in diabetes.

Abstract Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Abstract Develop a radiomics nomogram that integrates deep learning, radiomics, and clinical variables to predict epidermal growth factor receptor (EGFR) mutation status in patients with stage I non-small cell lung cancer (NSCLC). We retrospectively included 438 patients who underwent curative surgery and completed driver-gene mutation tests for stage I NSCLC from four academic medical centers. Predictive models were established by extracting and analyzing radiomic features in intratumoral, peritumoral, and habitat regions of CT images to identify EGFR mutation status in stage I NSCLC. Additionally, three deep learning models based on the intratumoral region were constructed. A nomogram was developed by integrating representative radiomic signatures, deep learning, and clinical features. Model performance was assessed by calculating the area under the receiver operating characteristic (ROC) curve. The established habitat radiomics features demonstrated encouraging performance in discriminating between EGFR mutant and wild-type, with predictive ability superior to other single models (AUC 0.886, 0.812, and 0.790 for the training, validation, and external test sets, respectively). The radiomics-based nomogram exhibited excellent performance, achieving the highest AUC values of 0.917, 0.837, and 0.809 in the training, validation, and external test sets, respectively. Decision curve analysis (DCA) indicated that the nomogram provided a higher net benefit than other radiomics models, offering valuable information for treatment.

Persistent inflammatory responses often occur when bacteria and other microorganisms frequently invade and colonize open wounds and eventually result in the formation of chronic wounds. Therefore, achieving real-time detection of invasive bacteria accurately and promptly is essential for efficient wound management and accelerating the healing process. Recently, flexible wearable sensors have garnered significant attention, especially those designed for monitoring real-time biophysical or biochemical signals in wound sites in a minimally invasive manner. They provide more precise and continuous monitoring data, making them as emerging tools for clinical diagnostics. In this review, we first discuss the species and community distribution of different types of bacteria in chronic wounds. Next, we introduce currently developed techniques for detecting bacteria at wound sites. Following that, we discuss the recent progress and unresolved issues of various flexible wearable sensors in detecting bacteria at wound sites. We believe that this review can provide meaningful guidance for the development of flexible wearable sensors for bacteria detection.

Abstract Background Bladder cancer (BC) is among the most prevalent malignant urothelial tumors globally, yet the prognosis for patients with muscle-invasive bladder cancer (MIBC) remains dismal, with a very poor 5-year survival rate. Consequently, identifying more effective and less toxic chemotherapeutic alternatives is critical for enhancing clinical outcomes for BC patients. Isorhapontigenin (ISO), a novel stilbene isolated from a Gnetum found in certain provinces of China, has shown potential as an anticancer agent due to its diverse anticancer activities. Despite its promising profile, the specific anticancer effects of ISO on BC and the underlying mechanisms are still largely unexplored. Methods The anchorage-independent growth, migration and invasion of BC cells were assessed by soft agar and transwell invasion assays, respectively. The RNA levels of SOX2, miR-129 and SNHG1 were quantified by qRT-PCR, while the protein expression levels were validated through Western blotting. Furthermore, methylation-specific PCR was employed to assess the methylation status of the miR-129 promoter. Functional assays utilized siRNA knockdown, plasmid-mediated overexpression, and chemical inhibition approaches. Results Our study demonstrated that ISO treatment significantly reduced SNHG1 expression in a dose- and time-dependent manner in BC cells, leading to the inhibition of anchorage-independent growth and invasion in human basal MIBC cells. This effect was accompanied by the downregulation of MMP-2 and MMP-9 and the upregulation of the tumor suppressor PTEN. Further mechanistic investigations revealed that SOX2, a key upstream regulator of SNHG1, played a crucial role in mediating the ISO-induced transcriptional suppression of SNHG1. Additionally, we found that ISO treatment led to a decrease in DNMT3b protein levels, which in turn mediated the hypomethylation of the miR-129 promoter and the subsequent suppression of SOX2 mRNA 3’-UTR activity, highlighting a novel pathway through which ISO exerts its anticancer effects. Conclusions Collectively, our study highlights the critical role of SNHG1 downregulation as well as its upstream DNMT3b/miR-129/SOX2 axis in mediating ISO anticancer activity. These findings not only elucidate the mechanism of action of ISO but also suggest novel targets for BC therapy.

Abstract In recent years, there has been a significant increase in the design of neural network models for solving math word problems (MWPs). These neural solvers have been designed with various architectures and evaluated on diverse datasets, posing challenges in fair and effective performance evaluation. This paper presents a comparative study of representative neural solvers, aiming to elucidate their technical features and performance variations in solving different types of MWPs. Firstly, an in-depth technical analysis is conducted from the initial deep neural solver DNS to the state-of-the-art GPT-4. To enhance the technical analysis, a unified framework is introduced, which comprises highly reusable modules decoupled from existing MWP solvers. Subsequently, a testbed is established to conveniently reproduce existing solvers and develop new solvers by combing these reusable modules, and finely regrouped datasets are provided to facilitate the comparative evaluation of the designed solvers. Then, comprehensive testing is conducted and detailed results for eight representative MWP solvers on five finely regrouped datasets are reported. The comparative analysis yields several key findings: (1) Pre-trained language model-based solvers demonstrate significant accuracy advantages across nearly all datasets, although they suffer from limitations in math equation calculation. (2) Models integrated with tree decoders exhibit strong performance in generating complex math equations. (3) Identifying and appropriately representing implicit knowledge hidden in problem texts is crucial for improving the accuracy of math equation generation. Finally, the paper also discusses the major technical challenges and potential research directions in this field. The insights gained from this analysis offer valuable guidance for future research, model development, and performance optimization in the field of math word problem solving.

Abstract The dry reforming of methane provides an attractive route to convert greenhouse gases (CH4 and CO2) into valuable syngas, so as to resolve the carbon cycle and environmental issues. However, the development of high-performance catalysts remains a huge challenge. Herein, we report a 0.6% Ir/CeO2−x catalyst with a metal-support interface structure which exhibits high CH4 (~72%) and CO2 (~82%) conversion and a CH4 reaction rate of ~973 μmolCH4 gcat −1 s−1 which is stable over 100 h at 700 °C. The performance of the catalyst is close to the state-of-the-art in this area of research. A combination of in situ spectroscopic characterization and theoretical calculations highlight the importance of the interfacial structure as an intrinsic active center to facilitate the CH4 dissociation (the rate-determining step) and the CH2* oxidation to CH2O* without coke formation, which accounts for the long-term stability. The catalyst in this work has a potential application prospect in the field of high-value utilization of carbon resources.

In this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and posterior foregut by treatment with FGF7, SANT1, LDN193189, PdBU, and retinoic acid (RA). The subsequent endocrine generation and directed SC-delta cell induction is achieved by a combined treatment of the FGF7 with FGF2 during stage 4 and 5, together with RA, XXI, ALK5 inhibitor II, SANT1, Betacellulin and LDN193189. The planar cultivation is converted to a suspended system after stage 5, allowing cells to aggregate into delta cell-containing spheroids. The differentiation takes approximately 4-5 weeks for delta cell generation and an additional 1-2 weeks for cell expansion and evaluation. We believe that this amenable and simplified protocol can provide a stable source of SC-delta cells from efficient differentiation, facilitating further investigation of the physiological role of delta cells as well as refinement of islet cell therapeutic strategies.

Abstract With the aging and obesity era, the increasing incidence of diabetes and diabetic complications, especially the non‐healing wounds, imposes a serious economic burden on both patients and society. The complex microenvironments, including hyperglycemia, bacterial infection, ischemia, and nerve damage, lead to the prolonged inflammation and proliferation phase of diabetic wounds. Mesenchymal stem cell‐derived small extracellular vesicles (MSC‐sEVs), which contain a rich variety of therapeutic molecules, have been chased for decades because of their potential roles in cellular communication, tissue regeneration, and drug delivery. As powerful tools for the controlled‐sustained release of sEVs, biocompatible hydrogels have been applied in a wide range of biomedical applications. Herein, we first summarize the pathological features of diabetic wounds, such as angiopathy, neuropathy, and immune cell dysfunction. Then, we discuss the biological properties, therapeutic performance, and stability of pure MSC‐sEVs. After that, we discuss the components, application patterns, and responsiveness of hydrogels. Next, we discuss the loading avenues of MSC‐sEVs into hydrogel, the release behaviors of sEVs from hydrogels, and the influence of the crosslinking method on the hydrogel‐sEV composites. Finally, we provide an overview of the current applications of hydrogels loaded with MSC‐sEVs as a novel cell‐free tissue engineering system in managing diabetic wounds and propose the critical unsolved issues. This review is expected to provide meaningful guidance for developing a novel cell‐free tissue engineering system for diabetic wound management.

Abstract Perovskite oxides and organic–inorganic halide perovskite materials, with numerous fascinating features, have been subjected to extensive studies. Most of the properties of perovskite materials are dependence on their ferroelectricity that denoted by remanent polarization (Pr). Thus, the increase of Pr in perovskite films is mainly an effort in material physics. At present, commonplace improvement schemes, i.e., controlling material crystallinity, and post‐annealing by using a high‐temperature process, are normally used. However, a simpler and temporal strategy for Pr improvement is always unavailable to perovskite material researchers. In this study, an organic coating layer, low‐temperature, and vacuum‐free strategy is proposed to improve the Pr, directly increasing the Pr from 36 to 56 µC cm−2. Further study finds that the increased Pr originates from the suppression of the oxygen defects and Ti defects. This organic coating layer strategy for passivating the defects may open a new way for the preparation of higher‐performance and cost‐effective perovskite products, further improving its prospective for application in the electron devices field.

Abstract The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Due to the detrimental effect of formaldehyde on DNA, ethanol has replaced formalin as the primary preservative for animal specimens. However, short-term formalin fixation of specimens might be applied during field collection. In an increasing number of studies, DNA extraction and sequencing have been successfully conducted from formalin-fixed specimens. Here the DNA from five specimens of Triplophysa dalaica (Kessler, 1876) were extracted and performed high-throughput sequencing. Four of the specimens underwent short-term fixation with formalin and were subsequently transferred to ethanol. One was continuously stored in ethanol. No significant difference of DNA quality and amount were observed among these samples. Followed by assembly and annotation, five mitochondrial genomes ranging in length from 16,569 to 16,572 bp were obtained. Additionally, previously published data of other individuals or species were included to perform phylogenetic analyses. In the reconstructed trees, all eight individuals of T. dalaica form a monophyletic group within the Triplophysa branch. The group is divided into three clades: (1) samples from the Yellow River, (2) those from the Yangtze River, and (3) those from the Haihe River, and the Lake Dali Nur. This study sheds initial light on the phylogeographic relationships among different populations of T. dalaica, and will support the research about its evolutionary history in the future.

Abstract Pseudomonas putida has become an increasingly important chassis for producing valuable bioproducts. This development is not least due to the ever‐improving genetic toolbox, including gene and genome editing techniques. Here, we present a novel, one‐plasmid design of a critical genetic tool, the pEMG/pSW system, guaranteeing one engineering cycle to be finalized in 3 days. The pEMG/pSW system proved in the last decade to be valuable for targeted genome engineering in Pseudomonas, as it enables the deletion of large regions of the genome, the integration of heterologous gene clusters or the targeted generation of point mutations. Here, to expedite genetic engineering, two alternative plasmids were constructed: (1) The sacB gene from Bacillus subtilis was integrated into the I‐SceI expressing plasmid pSW‐2 as a counterselection marker to accelerated plasmid curing; (2) double‐strand break introducing gene I‐sceI and sacB counterselection marker were integrated into the backbone of the original pEMG vector, named pEMG‐RIS. The single plasmid of pEMG‐RIS allows rapid genome editing despite the low transcriptional activity of a single copy of the I‐SceI encoding gene. Here, the usability of the pEMG‐RIS is shown in P. putida KT2440 by integrating an expression cassette including an msfGFP gene in 3 days. In addition, a large fragment of 12.1 kb was also integrated. In summary, we present an updated pEMG/pSW genome editing system that allows efficient and rapid genome editing in P. putida. All plasmids designed in this study will be available via the Addgene platform.

The understanding of the link between the gut-bone axis is growing yearly, but the mechanisms involved are not yet clear. Our study analyzed the role of Sestrin2 (SESN2)pathway in the gut-bone axis. We established an osteoarthritis (OA) model in Sprague-Dawley (SD) rats using the anterior cruciate ligament transection (ACLT) procedure, followed by a dietary intervention with varying levels of dietary fiber content for 8 weeks. By 16S rRNA sequencing of the gut microbiota, we found that high dietary fiber (HDF) intake could significantly increase the Bacillota-dominant gut microbiota. Meanwhile, enzyme linked immunosorbent assay (ELISA) and histological analysis showed that intervention with HDF could reduce the degree of bone and joint lesions and inflammation. We hypothesize that HDF increased the dominant flora of Bacillota, up-regulated the expression of SESN2 in knee joint, and reduced gut permeability, thereby reducing systemic inflammatory response and the degree of bone and joint lesions. Therefore, the present study confirms that changes in gut microbiota induced by increased dietary fiber intake delayed the onset of OA by promoting up-regulation of SESN2 expression at the knee joint to maintain chondrocyte activity and reduce synovial inflammation.

This article explores the technology of recognizing non-cooperative communication behavior, with a specific emphasis on analyzing communication station signals. Conventional techniques for analyzing signal data frames to determine their identity, while precise, do not have the ability to operate in real-time. In order to tackle this issue, we developed a pragmatic architecture for recognizing communication behavior and a system based on polling. The method utilizes a one-dimensional convolutional neural network (CNN) to segment data, hence improving its ability to recognize various communication activities. The study assesses the reliability of CNN in several real-world scenarios, examining its accuracy in the presence of noise interference, varying lengths of interception signals, interferences at different frequency points, and dynamic changes in outpost locations. The experimental results confirm the efficacy and dependability of the convolutional neural network in recognizing communication behavior in various contexts.

Abstract The peptidyl-prolyl cis-trans isomerase Pin1 is a pivotal therapeutic target in cancers, but the regulation of Pin1 protein stability is largely unknown. High Pin1 expression is associated with SUMO1-modified protein hypersumoylation in glioma stem cells (GSCs), but the underlying mechanisms remain elusive. Here we demonstrate that Pin1 is deubiquitinated and stabilized by USP34, which promotes isomerization of the sole SUMO E2 enzyme Ubc9, leading to SUMO1-modified hypersumoylation to support GSC maintenance. Pin1 interacts with USP34, a deubiquitinase with preferential expression and oncogenic function in GSCs. Such interaction is facilitated by Plk1-mediated phosphorylation of Pin1. Disruption of USP34 or inhibition of Plk1 promotes poly-ubiquitination and degradation of Pin1. Furthermore, Pin1 isomerizes Ubc9 to upregulate Ubc9 thioester formation with SUMO1, which requires CDK1-mediated phosphorylation of Ubc9. Combined inhibition of Pin1 and CDK1 with sulfopin and RO3306 most effectively suppresses orthotopic tumor growth. Our findings provide multiple molecular targets to induce Pin1 degradation and suppress hypersumoylation for cancer treatment.

There is a close relationship between potassium (K) and nitrogen (N). However, the roles of K under high N conditions remain unclear. Using a hydroponics approach, we monitored the morphological, physiological, and molecular changes in M9T337 apple (Malus domestica) rootstocks under different nitrate (10 and 30 mmol·L−1 NO3−) and K supply (0.5, 6, 10, and 20 mmol·L−1 K+) conditions. Results revealed that high nitrate inhibited the root growth of M9T337 rootstocks, downregulated the expressions of K transporter genes (MdPT5, MdHKT1, and MdATK1), and reduced the net NO3− and K+ influx at the surface of roots, thereby resulting in an N/K imbalance in rootstocks. Further investigation showed that 10 mmol·L−1 K increased the activity of N metabolic enzymes (NR, GS, NiR, and GOGAT), upregulated the expressions of genes related to nitrate uptake and transport (MdNRT1.1, MdNRT1.2, MdNRT1.5, and MdNRT2.4), promoted 15N transport from the roots to the shoots, optimized leaf N distribution, and improved photosynthetic N utilization efficiency under high nitrate conditions. These results suggest that the negative effects of high nitrate may be related to the N/K imbalance and that reducing N/K in plants by increasing K supply level can effectively alleviate the inhibition of N assimilation by high nitrate stress.

Abstract Copper-based catalysts serve as the predominant methanol steam reforming material although several fundamental issues remain ambiguous such as the identity of active center and the aspects of reaction mechanism. Herein, we prepare Cu/Cu(Al)O x catalysts with amorphous alumina-stabilized Cu2O adjoining Cu nanoparticle to provide Cu0−Cu+ sites. The optimized catalyst exhibits 99.5% CH3OH conversion with a corresponding H2 production rate of 110.8 μmol s−1 gcat −1 with stability over 300 h at 240 °C. A binary function correlation between the CH3OH reaction rate and surface concentrations of Cu0 and Cu+ is established based on kinetic studies. Intrinsic active sites in the catalyst are investigated with in situ spectroscopy characterization and theoretical calculations. Namely, we find that important oxygen-containing intermediates (CH3O* and HCOO*) adsorb at Cu0−Cu+ sites with a moderate adsorption strength, which promotes electron transfer from the catalyst to surface species and significantly reduces the reaction barrier of the C−H bond cleavage in CH3O* and HCOO* intermediates.

Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels. Nevertheless, the mechanism responsible for this dynamic insulin secretion has not been completely understood, particularly at the single islet level. In this study, we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion (GSIS) at the single islet level. With the utilization of this platform, we evaluated dynamic GSIS from single islets isolated from both normal and diabetic rats. Our results demonstrate that islets can be categorized into three types based on their dynamic GSIS: Type I exhibits a biphasic GSIS profile with a fast first phase and flat second phase; Type II also has a biphasic GSIS profile with a fast first phase but a slow increased second phase; Type III displays only a slowly increased second phase and lacks a fast first phase. RNA sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets, respectively. Moreover, our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin secretion. Furthermore, we revealed that diabetic islets exhibit only the type I GSIS response, indicating a deliberate impairment of the second phase of insulin secretion. Together, this device serves as a crucial tool in the research field of islets and diabetes, allowing researchers to investigate islet functional heterogeneity and identity at the single islet level.

Solving arithmetic word problems ($ AWPs $) that involve deep implicit relations can be quite challenging. However, the paper proposed two approaches to tackle this issue. The first approach used the modifier-to-matrix ($ MTM $) model to extract noun modification components from the problem text. Specifically, a missing entity recovery ($ MER $) model translated explicit expressions into a node dependency graph ($ NDG $). The nodes on the graph then recursively acquired connections from the knowledge base through the $ MER $ model until the goal was achieved with a known quantity. The solving engine then selected the appropriate knowledge as the prompt. The second approach proposed in the paper was a comprehensive one that combined explicit and implicit knowledge to enhance reasoning abilities. The experimental results of the dataset demonstrate that the proposed algorithm is superior to the baseline algorithms in solving $ AWPs $ that require deep implicit relations.

Abstract Acute myocardial infarction (AMI) is a life-threatening disease when sudden blockage of coronary artery occurs. As the most specific biomarker, cardiac troponin I (cTnI) is usually checked separately to diagnose or eliminate AMI, and achieving the accurate detection of cTnI is of great significance to patients’ life and health. Compared with other methods, fluorescent detection has the advantages of simple operation, high sensitivity and wide applicability. However, due to the strong fluorescence interference of biological molecules in body fluids, it is often difficult to obtain high sensitivity. In order to solve this problem, in this study, surface acoustic wave separation is designed to purify the target to achieve more sensitive detection performance of fluorescent detection. Specifically, the interference of background noise is almost completely removed on a microfluidic chip by isolating microbeads through acoustic radiation force, on which the biomarkers are captured by the immobilized detection probe. And then, the concentration of cTnI in human serum is detected by the fluorescence intensity change of the isolated functionalized beads. By this way, the detection limit of our biosensor calculated by 3σ/K method is 44 pg/mL and 0.34 ng/mL in PBS buffer and human serum respectively. Finally, the reliability of this method has been validated by comparison with clinical tests from the nephelometric analyzer in hospital.

The rational matching of urban land and population has become an important prerequisite for sustainable urban development. In this paper, the traditional urban land scale elasticity model was improved, and combined with the gravity model, the spatial interaction between land expansion and population change in 618 cities in China during the period 2006–2021 was investigated. The geographical detector method was used to reveal what drives them. The main results were as follows: (1) China’s urban land expansion rate was 1.83 times faster than the population growth rate during 2006–2021. After the implementation of the New-type Urbanisation Plan in 2014, the ratio of land expansion rate to population growth rate dropped from 2.46 to 1.12. (2) Among the six interaction types identified, land rapid expansion is the most significant, accounting for 41.59% of urban samples. (3) The geographical detector method found that the indicators of urban development rights such as the level of administrative hierarchy and the ratio of fiscal revenue to fiscal expenditure were the main factors affecting land expansion and that economic indicators such as gross domestic product and employment opportunities dominated population change. Fortunately, the intervention role of urban development rights has declined, and the constraints of market mechanisms, resources and environment have gradually become the dominant factors in urban land expansion and population change. These findings provide a theoretical basis for alleviating the human–land contradiction and achieving sustainable urban development.

The α-diimine late transition metal catalyst represents a new strategy for the synthesis of atactic polypropylene elastomer. Taking into account the properties of the material, enhancing the molecular weight of polypropylene at an elevated temperature through modifying the catalyst structure, and further increasing the activity of α-diimine catalyst for propylene polymerization, are urgent problems to be solved. In this work, two α-diimine nickel(II) catalysts with multiple hydroxymethyl phenyl substituents were synthesized and used for propylene homopolymerization. The maximum catalytic activity was 5.40 × 105 gPP/molNi·h, and the activity was still maintained above 105 gPP/molNi·h at 50 °C. The large steric hindrance of catalysts inhibited the chain-walking and chain-transfer reactions, resulting in polypropylene with high molecular weights (407~1101 kg/mol) and low 1,3-enchainment content (3.57~16.96%) in toluene. The low tensile strength (0.3~1.0 MPa), high elongation at break (218~403%) and strain recovery properties (S.R. ~50%, 10 tension cycles) of the resulting polypropylenes, as well as the visible light transmittance of approximately 90%, indicate the characteristics of the transparent elastomer.

Abstract Background Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. Methods Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF‐κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. Result Compared to the RA and IH groups, HDM‐treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF‐κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). Conclusion IHP treatment potentially exacerbates HDM‐induced airway inflammation in asthma, with the involvement of NF‐κB, particularly under high‐dose allergen stimulation.

IntroductionLung adenocarcinoma (LUAD) is a prevalent form of lung cancer originating from lung glandular cells with low survival rates despite recent therapeutic advances due to its diverse and complex nature. Recent evidence suggests a link between ferroptosis and the effectiveness of anti-PD-L1 therapy, with potential synergistic effects.MethodsOur study comprehensively analyzed the expression patterns of ferroptosis regulators in LUAD and their association with prognosis and PD-L1 expression. Furthermore, we identified two distinct subtypes of LUAD through consensus clustering of ferroptosis regulators, revealing significant tumor heterogeneity, divergent PD-L1 expression, and varying prognoses between the subtypes.ResultsAmong the selected ferroptosis regulators, SLC7A11 emerged as an independent prognostic marker for LUAD patients and exhibited a negative correlation with PD-L1 expression. Subsequent investigations revealed high expression of SLC7A11 in the LUAD population. In vitro experiments demonstrated that overexpression of SLC7A11 led to reduced PD-L1 expression and inhibited ferroptosis in A549 cells, underscoring the significant role of SLC7A11 in LUAD. Additionally, pan-cancer analyses indicated an association between SLC7A11 and the expression of immune checkpoint genes across multiple cancer types with poor prognoses.DiscussionFrom a clinical standpoint, these findings offer a foundation for identifying and optimizing potential combination strategies to enhance the therapeutic effectiveness of immune checkpoint inhibitors and improve the prognosis of patients with LUAD.

Abstract Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin‐binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self‐renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Background: Nickel is a confirmed human lung carcinogen. Nonetheless, the molecular mechanisms driving its carcinogenic impact on lung tissue remain poorly defined. In this study, we assessed SESN2 expression and the signaling pathways responsible for cellular transformation in human bronchial epithelial cells (HBECs) as a result of nickel exposure. Methods: We employed the Western blotting to determine the induction of SESN2 by nickel. To clarify the signaling pathways leading to cellular transformation following nickel exposure, we applied techniques such as gene knockdown, methylation-specific PCR, and chromatin immunoprecipitation. Result: Exposure to nickel results in the upregulation of SESN2 and the initiation of autophagy in human bronchial epithelial cells (HBECs). This leads to degradation of HUR protein and consequently downregulation of USP28 mRNA, PP2AC protein, β-catenin protein, and diminished VHL transcription, culminating in the accumulation of hypoxia-inducible factor-1α (HIF-1α) and the malignant transformation of these cells. Mechanistic studies revealed that the increased expression of SESN2 is attributed to the demethylation of the SESN2 promoter induced by nickel, a process facilitated by decreased DNA methyl-transferase 3 A (DNMT3a) expression, while The downregulation of VHL transcription is linked to the suppression of the PP2A-C/GSK3β/β-Catenin/C-Myc pathway. Additionally, we discovered that SESN2-mediated autophagy triggers the degradation of HUR protein, which subsequently reduces the stability of USP28 mRNA and inhibits the PP2A-C/GSK3β/β-Catenin pathway and c-Myc transcription in HBECs post nickel exposure. Conclusion: Our results reveal that nickel exposure leads to the downregulation of DNMT3a, resulting in the hypomethylation of the SESN2 promoter and its protein induction. This triggers autophagy-dependent suppression of the HUR/USP28/PP2A/β-Catenin/c-Myc pathway, subsequently leading to reduced VHL transcription, accumulation of HIF-1α protein, and the malignant transformation of human bronchial epithelial cells (HBECs). Our research offers novel insights into the molecular mechanisms that underlie the lung carcinogenic effects of nickel exposure. Specifically, nickel induces aberrant DNA methylation in the SESN2 promoter region through the decrease of DNMT3a levels, which ultimately leads to HIF-1α protein accumulation and the malignant transformation of HBECs. Specifically, nickel initiates DNA-methylation of the SESN2 promoter region by decreasing DNMT3a, ultimately resulting in HIF-1α protein accumulation and malignant transformation of HBECs. This study highlights DNMT3a as a potential prognostic biomarker or therapeutic target to improve clinical outcomes in lung cancer patients.

The key to promoting intelligent construction is to integrate the digital twin technology form the operation mode of virtual and real integration. And the industrial metaverse based on digital twin is the future development direction of intelligent mining face. The concept of virtual and real integration operation mode of fully-mechanized mining face based on virtual reality-digital twin-cyber physical system-industrial metaverse is proposed. It has six connotation characteristics, such as display and off-line simulation, monitoring and auxiliary operation, online simulation and preview. It is an evolution process from low-level display simulation to high-level deep integration function. Finally, it have four abilities : the ability of reproduction mapping from real to virtual precision, the ability of reasoning and forecasting decision-making in virtual iteration, the ability of reproduction control from virtual to real, the ability of seamless cooperation between virtual and real human-computer, and the ability of lean management. The four capabilities of industrial metaverse and the key technologies to realize industrial metaverse are analyzed.Based on the existing monitoring, decision-making and control capabilities, AR remote assistance technology that can strengthen the cooperation ability between field operators and remote operators, robot cooperation technology that can strengthen the safety of operators, and virtual human technology that can use AI-driven operation in virtual space are integrated to build a hydraulic support adjusting experimental system based on industrial metaveise,and preliminary understanding of the application of industrial metaverse in coal mining.

Water conservation is an essential parameter for maintaining the ecological balance. The Three-River Source Region (TRSR) cannot be an exception, since it is one of the most influential water conservation reserves in the Qinghai–Tibet Plateau in China. Therefore, the realization of its scientific significance can determine its future regional sustainable development and the optimal allocation of water resources. The study of the past is critical to predict the future temporal and spatial changes in the water conservation of the TRSR. The first task of this study was to obtain the optimal runoff simulations in the TRSR from 1981 to 2014 by calibrating the adjustable the parameters of the Soil and Water Assessment Tool (SWAT) model. Then, the water conservation of the TRSR from 1981 to 2014 was quantified. Finally, the future water conservation of the TRSR was also predicted using the optimal SWAT model. The predication took into consideration the three terms including the near-term (2015–2044), mid-term (2045–2074), and long-term (2075–2099) in three different climate scenarios of SSP1-1.9 (SSP119), SSP2-4.5 (SSP245), and SSP5-8.5 (SSP585). The main findings are as follows: (1) both the coefficient of determination (R2) and Nash–Sutcliffe efficiency coefficient (NSE) for runoff simulation on the three sub-basins reached above 0.78 during the calibration and validation periods, which indicates the reasonableness of the SWAT model in the TRSR. (2) From 1981 to 2014, the water conservation capacity of the TRSR showed an increasing trend (0.5135 mm/year), and its changes had significant positive correlations with precipitation and temperature. The Yellow River Source (YR) and the Yangtze River Source (YZ) had the strongest and weakest water conservation capacities, respectively. (3) From 2015 to 2099, the water conservation in the TRSR in the SSP119, SSP245, and SSP585 scenarios decreased first and then increased, increased first and then decreased, and increased steadily, respectively.

Thin-walled concrete-filled steel tubes are efficient and economical with promising applications in civil and light industrial buildings. However, their local buckling resistance and deformation capacity are low, which adversely affects the seismic safety of structures. There are relatively few studies on thin-walled concrete-filled steel tubular columns with ultra-large diameter-to-thickness ratios, and there is also a lack of relevant experimental research on them. In this study, horizontal hysteresis tests were conducted on concrete columns with a large diameter-to-thickness ratio. The seismic performances of regular and straight-ribbed specimens were analyzed and compared, including the analyses of load-displacement hysteresis curves, strain distribution, skeleton curves, ductility, and energy dissipation capacity. Using these results, a restoring force model for concrete columns with a large diameter-to-thickness ratio was established. The findings indicate that under horizontal loading, the ductility of concrete columns with a regular thin-walled steel tube is 3.9, with an equivalent viscous damping coefficient of 1.65. Meanwhile, the ultimate bearing capacity is 201 kN. After adding stiffening ribs, the ultimate bearing capacity reaches 266 kN and the ductility coefficient reaches 4.4, resulting in the stiffeners increasing the ultimate bearing capacity and ductility by >30% and 12.8%, respectively. However, they have a less pronounced effect on deformation and energy dissipation. Building on these research outcomes, we propose a dimensionless three-line skeleton curve model and a restoring force model. The calculation results from these models align well with the test results, offering valuable insights for the seismic safety analysis of real-world engineering structures.

The effect of H2 activation on the performance of CuFeOx catalyst for low-temperature CO oxidation was investigated. The characterizations of XRD, XPS, H2-TPR, O2-TPD, and in situ DRIFTS were employed to establish the relationship between physicochemical property and catalytic activity. The results showed that the CuFeOx catalyst activated with H2 at 100 °C displayed higher performance, which achieved 99.6% CO conversion at 175 °C. In addition, the H2 activation promoted the generation of Fe2+ species, and more oxygen vacancy could be formation with higher concentration of Oα species, which improved the migration rate of oxygen species in the reaction process. Furthermore, the reducibility of the catalyst was enhanced significantly, which increased the low-temperature activity. Moreover, the in situ DRIFTS experiments revealed that the reaction pathway of CO oxidation followed MvK mechanism at low temperature (+-CO and carbonate species were the main reactive intermediates, and the H2 activation increased the concentration of Cu+ species and accelerated the decomposition carbonate species, thus improving the catalytic performance effectively.

Abstract Background Nucleus pulposus cell (NPC) death and progressive reduction play important roles in intervertebral disc degeneration (IVDD). As part of a damage-associated molecular pattern, mitochondrial DNA (mtDNA) can be recognized by TLR9 and triggers the expression of NF-κB and NLRP3 inflammasomes, inducing pyroptosis and inflammatory response. However, whether mtDNA induces NPC pyroptosis via the TLR9-NF-κB-NLRP3 axis and promotes IVDD remains uncertain. Methods We constructed an in vitro NPC oxidative stress injury model to clarify the mechanism of mtDNA release, TLR9-NF-κB signaling pathway activation, and NPC injury. We further verified the mechanism of action underlying the inhibition of mtDNA release or TLR9 activation in NPC injury in vitro. We then constructed a rat punctured IVDD model to understand the mechanism inhibiting mtDNA release and TLR9 activation in IVDD. Results We used human NP specimen assays to show that the expression levels of TLR9, NF-κB, and NLRP3 inflammasomes correlated with the degree of IVDD. We demonstrated that mtDNA mediated TLR9-NF-κB-NLRP3 axis activation in oxidative stress-induced human NPC pyroptosis in vitro. Oxidative stress can damage the mitochondria of NPCs, causing the opening of the mitochondrial permeability transition pores (mPTP) and leading to the release of mtDNA into the cytosol. Furthermore, inhibition of mPTP opening or TLR9 activation blocked TLR9-NF-κB-NLRP3 axis activation and thereby mediated NPC pyroptosis and IVDD. Conclusion mtDNA plays a key role in mediating NPC pyroptosis and IVDD via the TLR9-NF-κB-NLRP3 axis. Our findings provide new potential targets for IVDD.

Abstract The metal-support interaction (MSI) in heterogeneous catalysts plays a crucial role in reforming reaction to produce renewable hydrogen, but conventional objects are limited to single metal and support. Herein, we report a type of RhNi/TiO2 catalysts with tunable RhNi-TiO2 strong bimetal-support interaction (SBMSI) derived from structure topological transformation of RhNiTi-layered double hydroxides (RhNiTi-LDHs) precursors. The resulting 0.5RhNi/TiO2 catalyst (with 0.5 wt.% Rh) exhibits extraordinary catalytic performance toward ethanol steam reforming (ESR) reaction with a H2 yield of 61.7%, a H2 production rate of 12.2 L h−1 gcat −1 and a high operational stability (300 h), which is preponderant to the state-of-the-art catalysts. By virtue of synergistic catalysis of multifunctional interface structure (Rh-Ni δ−-O v -Ti3+; O v denotes oxygen vacancy), the generation of formate intermediate (the rate-determining step in ESR reaction) from steam reforming of CO and CH x is significantly promoted on 0.5RhNi/TiO2 catalyst, accounting for its ultra-high H2 production.

Parkinson’s disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

Abstract The use of gaseous and air-captured CO2 for technical biosynthesis is highly desired, but elusive so far due to several obstacles including high energy (ATP, NADPH) demand, low thermodynamic driving force and limited biosynthesis rate. Here, we present an ATP and NAD(P)H-free chemoenzymatic system for amino acid and pyruvate biosynthesis by coupling methanol with CO2. It relies on a re-engineered glycine cleavage system with the NAD(P)H-dependent L protein replaced by biocompatible chemical reduction of protein H with dithiothreitol. The latter provides a higher thermodynamic driving force, determines the reaction direction, and avoids protein polymerization of the rate-limiting enzyme carboxylase. Engineering of H protein to effectively release the lipoamide arm from a protected state further enhanced the system performance, achieving the synthesis of glycine, serine and pyruvate at g/L level from methanol and air-captured CO2. This work opens up the door for biosynthesis of amino acids and derived products from air.

Abstract The increased use of low‐dose computed tomography screening has led to more frequent detection of early stage lung tumors, including minimally invasive adenocarcinoma (MIA). To unravel the intricacies of tumor cells and the immune microenvironment in MIA, this study performs a comprehensive single‐cell transcriptomic analysis and profiles the transcriptomes of 156,447 cells from fresh paired MIA and invasive adenocarcinoma (IA) tumor samples, peripheral blood mononuclear cells, and adjacent normal tissue samples from three patients with synchronous multiple primary lung adenocarcinoma. This study highlights a connection and heterogeneity between the tumor ecosystem of MIA and IA. MIA tumor cells exhibited high expression of aquaporin‐1 and angiotensin II receptor type 2 and a basal‐like molecular character. Furthermore, it identifies that cathepsin B+ tumor‐associated macrophages may over‐activate CD8+ T cells in MIA, leading to an enrichment of granzyme K+ senescent CD8+ T cells, indicating the possibility of malignant progression behind the indolent appearance of MIA. These findings are further validated in 34 MIA and 35 IA samples by multiplexed immunofluorescence. These findings provide valuable insights into the mechanisms that maintain the indolent nature and prompt tumor progression of MIA and can be used to develop more effective therapeutic targets and strategies for MIA patients.

Ocean wave energy is a new type of clean energy. To improve the power generation and wave energy conversion efficiency of the direct-drive wave power generation system, by addressing the issue of large output errors and poor system stability commonly associated with the currently used PID (proportional, integral, and derivative) control methods, this paper proposes a maximum power control method based on BP (back propagation) neural network PID control. Combined with Kalman filtering, this method not only achieves maximum power tracking but also reduces output ripple and tracking error, thereby enhancing the system’s control quality. This study uses a permanent magnet linear generator as the power generation device, establishes a system dynamics model, and predicts the main frequency of irregular waves through the Fast Fourier Transform method. It designs a desired current tracking curve that meets the maximum power strategy. On this basis, a comparative analysis of the control accuracy and stability of three control methods is conducted. The simulation results show that the BP neural network PID control method improves power generation and exhibits better accuracy and stability.

Point cloud-based detection focuses on land traffic, rarely marine, facing issues with ships: it struggles in bad weather due to reliance on adverse weather data and fails to detect ships effectively due to overlooking size and appearance differences. Addressing the above challenges, our work introduces point cloud data of marine scenarios under realistically simulated adverse weather conditions and a dedicated Ship Detector tailored for marine environments. To adapt to various maritime weather conditions, we simulate realistic rain and fog in collected marine scene point cloud data. Additionally, addressing the issue of losing geometric and height information during feature extraction for large objects, we propose a Ship Detector. It employs a dual-branch sparse convolution layer for extracting multi-scale 3D feature maps, effectively minimizing height information loss. Additionally, a multi-scale 2D convolution module is utilized, which encodes and decodes feature maps and directly employs 3D feature maps for target prediction. To reduce dependency on existing data and enhance model robustness, our training dataset includes simulated point cloud data representing adverse weather conditions. In maritime point cloud ship detection, our Ship Detector, compared to adjusted small object detectors, demonstrates the best performance.

Introduction: Stroke survivors often have motor impairments and related functional deficits. Transcranial Electrical Stimulation (tES) is a rapidly evolving field that offers a wide range of capabilities for modulating brain function, and it is safe and inexpensive. It has the potential for widespread use for post-stroke motor recovery. Transcranial Direct Current Stimulation (tDCS), Transcranial Alternating Current Stimulation (tACS), and Transcranial Random Noise Stimulation (tRNS) are three recognized tES techniques that have gained substantial attention in recent years but have different mechanisms of action. tDCS has been widely used in stroke motor rehabilitation, while applications of tACS and tRNS are very limited. The tDCS protocols could vary significantly, and outcomes are heterogeneous. Purpose: the current review attempted to explore the mechanisms underlying commonly employed tES techniques and evaluate their prospective advantages and challenges for their applications in motor recovery after stroke. Conclusion: tDCS could depolarize and hyperpolarize the potentials of cortical motor neurons, while tACS and tRNS could target specific brain rhythms and entrain neural networks. Despite the extensive use of tDCS, the complexity of neural networks calls for more sophisticated modifications like tACS and tRNS.

Abstract Objectives To reveal the relationship between the fibulin‐2 protein and immune dysfunction after bone trauma. Methods Individuals who were admitted to the study were divided into a bone trauma group, a recovered from bone trauma group and a volunteer without bone trauma group based on the reason for admission. Fibulin‐2 levels in the three groups were compared. Fibulin‐2‐knockout (fibulin‐2−/−) mice and wild‐type (WT) mice were used to detect susceptibility to infection. Hematoxylin and eosin (HE) staining and immunohistochemical staining were employed to observe pathological changes in each organ from fibulin‐2−/− mice and WT mice. Results In total, 132 patients were enrolled in this study. The fibulin‐2 level in the bone trauma group was lower than that in the recovered bone trauma group (3.39 ± 1.41 vs. 4.30 ± 1.38 ng/mL, t = 2.948, p

Abstract Diabetes mellitus (DM) is a disease caused by dysfunction or disruption of pancreatic islets. The advent and development of microfluidic organoids-on-a-chip platforms have facilitated reproduce of complex and dynamic environment for tissue or organ development and complex disease processes. For the research and treatment of DM, the platforms have been widely used to investigate the physiology and pathophysiology of islets. In this review, we first highlight how pancreatic islet organoids-on-a-chip have improved the reproducibility of stem cell differentiation and organoid culture. We further discuss the efficiency of microfluidics in the functional evaluation of pancreatic islet organoids, such as single-islet-sensitivity detection, long-term real-time monitoring, and automatic glucose adjustment to provide relevant stimulation. Then, we present the applications of islet-on-a-chip technology in disease modeling, drug screening and cell replacement therapy. Finally, we summarize the development and challenges of islet-on-a-chip and discuss the prospects of future research. Graphical Abstract

BackgroundChronic wounds are a complex medical problem. With the difficulty of skin healing, the microbial ecology of chronic wounds is an essential factor affecting wound healing. High-throughput sequencing (HTS) technology is a vital method to reveal the microbiome diversity and population structure of chronic wounds.ObjectiveThe aim of this paper was to delineate the scientific output characteristics, research trends, hotspots and frontiers of HTS technologies related to chronic wounds globally over the past 20 years.MethodsWe searched the Web of Science Core Collection (WoSCC) database for articles published between 2002 and 2022 and their full record information. The Bibliometrix software package was used to analyze bibliometric indicators and VOSviewer visualization analysis results.ResultsUltimately, a total of 449 original articles were reviewed, and the results showed that the number of annual publications (Nps) about HTS associated with chronic wounds has steadily increased over the last 20 years. The United States and China produce the most articles and have the highest H-index, while the United States and England have the largest number of citations (Nc) in this field. The University of California, Wound Repair and Regeneration and National Institutes of Health Nih United States were the most published institutions, journals and fund resources, respectively. The global research could be divided into 3 clusters as follows: microbial infection of chronic wounds, the healing process of wounds and microscopic processes, skin repair mechanism stimulated by antimicrobial peptides and oxidative stress. In recent years, “wound healing”, “infections”, “expression”, “inflammation”, “chronic wounds”, “identification” and “bacteria” “angiogenesis”, “biofilms” and “diabetes” were the most frequently used keywords. In addition, research on “prevalence”, “gene expression”, “inflammation” and “infection” has recently become a hotspot.ConclusionsThis paper compares the research hotspots and directions in this field globally from the perspectives of countries, institutions and authors, analyzes the trend of international cooperation, and reveals the future development direction of the field and research hotspots of great scientific research value. Through this paper, we can further explore the value of HTS technology in chronic wounds to better solve the problem of chronic wounds.

Abstract Background Patients who do not respond to conservative treatment of the isthmus are often treated with surgery. We used direct repair plus intersegment pedicle screw fixation for the treatment of lumbar spondylolysis. The aim of this observational study was to assess the effects of this technique and evaluate various risk factors potentially predicting the probability of disc and facet joint degeneration after instrumentation. Methods The study included 54 male L5 spondylolysis patients who underwent pars repair and intersegment fixation using pedicle screws. Bony union was evaluated using reconstruction images of computed tomography. Radiographic changes, including disc height, vertebral slip, facet joint and disc degeneration in the grade of adjacent and fixed segments, were determined from before to final follow-up. Logistic regression analysis was performed to identify factors associated with the incidence of disc and facet joint degeneration. Results Bony union was achieved in all cases. Logistic regression analysis revealed that instrumentation durations of greater than 15.5 months and 21.0 months were significant risk factors for the incidence of L4/5 and L5S1 facet degeneration, respectively. Conclusions Intersegmental pedicle screw fixation provides good surgical outcomes and good isthmic bony union rates in patients with lumbar spondylolysis. The duration of fixation was confirmed as a risk factor for facet joint degeneration. Once bony union is achieved, instrument removal should be recommended.

BackgroundHere provides a complementary treatment, acupressure at the Qiu acupoint, a novel acupoint, which potentially alleviates renal colic.Materials and methods90 patients were included in this study. Acupressure-group patients (n = 46) were administered acupressure at the Qiu acupoint following a preset protocol. Parecoxib sodium-group patients (n = 44) were administered parecoxib sodium (40 mg) (via the direct intravenous route). The visual analog scale (VAS) was used to evaluate pain intensity at baseline and at 1, 5, 10, 20, 30, and 120 min after initiating the intervention. Linear mixed effects model was performed to detect the rate of decrease of VAS per time and their covariant effect on the efficacy of acupressure.ResultsNo significant statistical differences in baseline data and VAS scores were observed. The acupressure group obtained lower VAS scores at the 1st, 5th, 10th, and 20th minute than the parecoxib sodium group after initiating the intervention (mean: 4.33 vs. 7.61, mean difference (MD): 3.29, 95% CI: 0.23, 2.84; mean: 2.65 vs. 7.61, MD: 4.96, 95% CI: 4.44, 5.49; mean: 1.63 vs. 6.59, MD: 4.96, 95% CI: 4.48, 5.44; mean: 1.26 vs. 3.64 MD: 2.38, 95% CI: 1.87, 2.88; P < 0.05). The markedly effective rate was similar between the two groups. The linear mixed effects model demonstrated that acupressure at the Qiu point was significantly faster than parecoxib sodium in decreasing VAS scores with an estimate of –2.05 (95% CI: –2.51, –1.59, p = 0.000), especially within 10 minutes with an estimate of 0.18 (95% CI: 0.12, 0.25, p = 0.000).ConclusionAcupressure at the Qiu acupoint is significantly faster than parecoxib sodium in decreasing VAS scores within 10 minutes.Clinical trial registrationhttp://www.chictr.org.cn/, identifier 2100047168.

For monitoring the earthquake ground motion, it is essential to rapidly and accurately detecting P waves' arrival in the seismic signal. To detect the seismic events and pick phases' arrival, some traditional methods are based on the statistical theory, such as the short-term average and long-term average ratio (STA/LTA) method, the modified energy ratio (MER) method and the Akaike information criteria (AIC) method. However, when the seismic event occurred, the ground motion signal no longer obeys the normal distribution, and the probability distribution of the seismic signals is unknown or uncertainty. Due to these problems, the traditional methods are limited to pick P waves. A new P waves' picking method is proposed based on grey relational analysis. The method depends on the grey relational coefficients, which are calculated by a known template and the seismic signal. The grey relational coefficients represent the similarity between a chosen template and the seismic signal. The grey relational coefficients' changes represent the P waves' arrival. Therefore, by calculating the grey relational coefficients, the P waves can be detected with a given confidence level. Through the sample analysis of Wenchuan Ms.8.0 Earthquake's main-shock and its aftershocks, by the grey relational analysis (GRA) method the P waves' picking mean error is 0.02s and its variance error is 0.053s respectively, which performs better than the mean error (0.09s) and variance error (0.18s) by the AIC method. To verify the robustness of the GRA method some random noises were added to the original seismic data, and the P waves' picking were performed by both the GAR method and the AIC method. Then the variance error of the GRA method increased to 0.10s, which is also less than the variance error (0.22s) by the AIC method. The simulation results shows that the GRA method not only provides the better accuracy than the AIC method, but also is suitable for the continuous seismic signals. The GRA method is based on the non-statistical theory and will be a beneficial attempt for the EEW system.

This study analyzed the effect of different treatment methods in enzyme-induced carbonate precipitation (EICP) on the mechanical properties of soil. Soybean crude urease was used to catalyze the precipitation of calcium carbonate (CaCO3). A multiple-phase method was proposed and further compared with commonly practiced EICP treatment methods (including the one-phase method, two-phase method, and premix-and-compact method) from the aspects of chemical conversion efficiency, CaCO3 precipitation distribution, permeability, and unconfined compressive strength. Based on the findings, the characteristics of each method were further discussed and summarized. Although the enzymatic CaCO3 precipitation generated from all the treatment methods could potentiate the soil strength to a great or less degree, using the proposed multiple-phase method could bring about a high chemical conversion efficiency, uniform distribution of CaCO3 as well as preferable permeability retention. In addition, the multiple-phase method could significantly improve the efficiency of urease usage.