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Abstract Background Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage destruction and inflammation. CC chemokine receptor 1 (CCR1), a member of the chemokine family and its receptor family, plays a role in the autoimmune response. The impact of BX471, a specific small molecule inhibitor of CCR1, on CCR1 expression in cartilage and its effects on OA remain underexplored. Methods This study used immunohistochemistry (IHC) to assess CCR1 expression in IL-1β-induced mouse chondrocytes and a medial meniscus mouse model of destabilization of the medial meniscus (DMM). Chondrocytes treated with varying concentrations of BX471 for 24 h were subjected to IL-1β (10 ng/ml) treatment. The levels of the aging-related genes P16INK4a and P21CIP1 were analyzed via western blotting, and senescence-associated β-galactosidase (SA-β-gal) activity was measured. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan (AGG), and the transcription factor SOX9 were determined through western blotting and RT‒qPCR. Collagen II, matrix metalloproteinase 13 (MMP13), and peroxisome proliferator-activated receptor (PPAR)-γ expression was analyzed via western blot, RT‒qPCR, and immunofluorescence. The impact of BX471 on inflammatory metabolism-related proteins under PPAR-γ inhibition conditions (using GW-9662) was examined through western blotting. The expression of MAPK signaling pathway-related molecules was assessed through western blotting. In vivo, various concentrations of BX471 or an equivalent medium were injected into DMM model joints. Cartilage destruction was evaluated through Safranin O/Fast green and hematoxylin–eosin (H&E) staining. Results This study revealed that inhibiting CCR1 mitigates IL-1β-induced aging, downregulates the expression of iNOS, COX-2, and MMP13, and alleviates the IL-1β-induced decrease in anabolic indices. Mechanistically, the MAPK signaling pathway and PPAR-γ may be involved in inhibiting the protective effect of CCR1 on chondrocytes. In vivo, BX471 protected cartilage in a DMM model. Conclusion This study demonstrated the expression of CCR1 in chondrocytes. Inhibiting CCR1 reduced the inflammatory response, alleviated cartilage aging, and retarded degeneration through the MAPK signaling pathway and PPAR-γ, suggesting its potential therapeutic value for OA. Graphical Abstract

Abstract Small extracellular vesicle–derived microRNAs (sEV-miRNAs) have emerged as promising noninvasive biomarkers for early cancer diagnosis. Herein, we developed a molecular probe based on three-dimensional (3D) multiarmed DNA tetrahedral jumpers (mDNA-Js)-assisted DNAzyme activated by Na+, combined with a disposable paper-based electrode modified with a Zr-MOF–rGO–Au NP nanocomplex (ZrGA) to fabricate a novel biosensor for sEV-miRNAs Assay. Zr-MOF tightly wrapped by rGO was prepared via a one-step method, and it effectively aids electron transfer and maximizes the effective reaction area. In addition, the mechanically rigid, and nanoscale-addressable mDNA-Js assembled from the bottom up ensure the distance and orientation between fixed biological probes as well as avoid probe entanglement, considerably improving the efficiency of molecular hybridization. The fabricated bioplatform achieved the sensitive detection of sEV-miR-21 with a detection limit of 34.6 aM and a dynamic range from100 aM to 0.2 µM. In clinical blood sample tests, the proposed bioplatform showed results highly consistent with those of qRT-PCRs and the signal increased proportionally with the NSCLC staging. The proposed biosensor with a portable wireless USB-type analyzer is promising for the fast, easy, low-cost, and highly sensitive detection of various nucleic acids and their mutation derivatives, making it ideal for POC biosensing.

The treatment of wound inflammation is intricately linked to the concentration of reactive oxygen species (ROS) in the wound microenvironment. Among these ROS, H2O2 serves as a critical signaling molecule and second messenger, necessitating the urgent need for its rapid real-time quantitative detection, as well as effective clearance, in the pursuit of effective wound inflammation treatment. Here, we exploited a sophisticated 3D Cu2-xSe/GO nanostructure-based nanonzymatic H2O2 electrochemical sensor, which is further decorated with evenly distributed Pt nanoparticles (Pt NPs) through electrodeposition. The obtained Cu2-xSe/GO@Pt/SPCE sensing electrode possesses a remarkable increase in specific surface derived from the three-dimensional surface constructed by GO nanosheets. Moreover, the localized surface plasma effect of the Cu2-xSe nanospheres enhances the separation of photogenerated electron-hole pairs between the interface of the Cu2-xSe NPs and the Pt NPs. This innovation enables near-infrared light-enhanced catalysis, significantly reducing the detection limit of the Cu2-xSe/GO@Pt/SPCE sensing electrode for H2O2 (from 1.45 μM to 0.53μM) under NIR light. Furthermore, this biosensor electrode enables in-situ real-time monitoring of H2O2 released by cells. The NIR-enhanced Cu2-xSe/GO@Pt/SPCE sensing electrode provide a simple-yet-effective method to achieve a detection of ROS (H2O2、-OH) with high sensitivity and efficiency. This innovation promises to revolutionize the field of wound inflammation treatment by providing clinicians with a powerful tool for accurate and rapid assessment of ROS levels, ultimately leading to improved patient outcomes.

IntroductionEarly reading has gained significant attention in the academic community. With the increasing volume of literature on this subject, it has become crucial to assess the current research landscape and identify emerging trends.MethodsThis study utilized the dynamic topic model to analyze a corpus of 1,638 articles obtained from the Web of Science Core Collection to furnish a lucid understanding of the prevailing research and forecast possible future directions.ResultsOur in-depth assessment discerned 11 cardinal topics, among which notable ones were interventions' impacts on early reading competencies; foundational elements of early reading: phonological awareness, letters, and, spelling; and early literacy proficiencies in children with autism spectrum disorder. Although most topics have received consistent research attention, there has been a marked increase in some topics' popularity, such as foundational elements of early reading and early literary proficiencies in children with autism spectrum disorder. Conversely, other topics exhibited a downturn.DiscussionThis analytical endeavor has yielded indispensable insights for scholars, decision-makers, and field practitioners, steering them toward pivotal research interrogatives, focal interest zones, and prospective research avenues. As per our extensive survey, this paper is a pioneering holistic purview of the seminal areas of early reading that highlights expected scholarly directions.

Abstract Extreme surges and rainfall represent major driving factors for compound flooding in estuary regions along the Chinese coast. The combined effect of extreme surges and rainfall (that is, compound floods) might lead to greater impacts than if the drivers occurred in isolation. Hence, understanding the frequency and severity of compound flooding is important for improving flood hazard assessment and compound flood resilience in coastal cities. In this study, we examined the dependence between extreme surges and corresponding rainfall events in 26 catchments along the Chinese coastline during typhoon and non-typhoon seasons using copula functions, to identify where the two drivers more often occur together and the implication for flood management in these locations. We found that the interaction between flood drivers is statistically significant in 10 catchments located around Hainan Island (south) and Shanghai, where surge peaks occur mainly during the typhoon season and around the Bohai Sea (north), where surge peaks occur mainly during the non-typhoon season. We further applied the copula-based framework to model the dependence between surge peaks and associated rainfall and estimate their joint and conditional probability in two specific locations—Hainan Island and the Bohai Sea, where the correlation between flood drivers is statistically significant. We observed that in Hainan Island where most of the surge peaks occur during the typhoon season, extreme rainfall events during the typhoon season are generally more intense compared to annual maxima rainfall. In contrast, around the Bohai Sea where surge peaks occur mainly outside the typhoon season, rainfall is less intense than annual maxima rainfall. These results show that the interaction between extreme surges and rainfall can provide valuable insight when designing coastal and urban infrastructure, especially in highly populated urban areas prone to both coastal and pluvial flooding, such as many Chinese coastal cities.

Abstract Accurate and efficient detection of pathogenic bacteria plays a crucial role in the diagnosis of infectious diseases. However, rapid and highly sensitive detection of specific bacteria in clinical samples remains challenging. In this study, we developed a ratiometric dual‐signal electrochemical biosensor for ultrasensitive detection of pathogenic bacteria, based on an aptamer recognition‐induced rolling circle amplification (RCA)/G‐quadruplex strategy. On the surface of a gold electrode chip, we used an aptamer sequence (P1) conjugated to ferrocene (Fc) to capture the target bacterium. This capture released a different, previously bound sequence (P2) sequence that initiated the RCA/G‐quadruplex cascade, which, in the presence of potassium ions, was able to bind the electrochemical indicator methylene blue (MB). We integrated the signals from the loss of Fc and the appearance of MB (IMB/IFC ratio) to quantify the target bacteria concentration. This biosensor showed excellent detection performance and specificity, with a detection limit of 10 CFU/mL. Notably, it showed great diagnostic potential for clinical infectious diseases caused by pathogenic bacteria in precise/personalized medicine applications.

Free-living Symbiodinium, which forms symbiotic relationships with many marine invertebrates, plays an important role in the vast ocean. Nutrient levels have been shown to significantly impact microbial community structure and regulate algal communities. In this study, the bacterial community structure within the phycosphere of free-living Symbiodinium underwent significant changes in response to nutrient stimulation. Alteromonas exhibited dominance in Zobell 2216E broth nutrient stimulation concomitant with the demise of algal cells. Alteromonas abrolhosensis JY-JZ1, a marine bacterium isolated from the phycosphere of Symbiodinium, demonstrated an algicidal effect on Symbiodinium cells. Optical and scanning electron microscopy revealed that the algal cell membrane structure was disrupted, leading to intracellular leakage. Strain JY-JZ1 exerted its cytotoxicity by producing and secreting bioactive compounds into the supernatant. The marked declines in the chlorophyll a content, photosynthetic efficiency (Fv/Fm) and the electron transport rate (rETR) indicated that the photosynthetic system of Symbiodinium was damaged by JY-JZ1 supernatant. The observed elevation in levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) content suggested that the algal cells experienced oxidative stress. Moreover, the supernatant exhibited remarkable adaptability to temperature and pH. Additionally, it displayed exceptional algicidal efficacy against various harmful algae species. To the best of our knowledge, this study represents the first successful isolation of an algicidal bacterial strain from the phycosphere of free-living Symbiodinium and subsequent investigation into its mechanism for controlling Symbiodinium growth, thereby providing novel insights into algae-bacteria interactions. The remarkable algicidal efficacy exhibited by strain JY-JZ1 against other harmful algae species suggests its significant potential for harmful algal blooms (HABs) control.

The environmental and health impacts from the massive discharge of chemicals and subsequent pollution have been gaining increasing public concern. The unintended exposure to different pollutants, such as heavy metals, air pollutants and organic chemicals, may cause diverse deleterious effects on human bodies, resulting in the incidence and progression of different diseases. The article reviewed the outbreak of environmental pollution-related public health emergencies, the epidemiological evidence on certain pollution-correlated health effects, and the pathological studies on specific pollutant exposure. By recalling the notable historical life-threatening disasters incurred by local chemical pollution, the damning evidence was presented to criminate certain pollutants as the main culprit for the given health issues. The epidemiological data on the prevalence of some common diseases revealed a variety of environmental pollutants to blame, such as endocrine-disrupting chemicals (EDCs), fine particulate matters (PMs) and heavy metals. The retrospection of toxicological studies provided illustrative clues for evaluating ambient pollutant-induced health risks. Overall, environmental pollution, as the hidden culprit, should answer for the increasing public health burden, and more efforts are highly encouraged to strive to explore the cause-and-effect relationships through extensive epidemiological and pathological studies.

The Ti-(0–30)Nb-(2–11)Mo-3.5Ta (wt.%) alloys with the composition interval of 5.0 wt.% for Nb and 3.0 wt.% for Mo were prepared by hot isostatic pressing. The Ti–Nb–Mo–Ta alloys with high compressive strength and favorable ductility were obtained, which enabled the alloys to be used as novel structural or biomedical materials. The phase constituent, microstructure, and compressive properties were investigated. Although the compressive yield strength and the strain at failure showed different correlations to the Nb and Mo content, respectively, the two mechanical property parameters both showed distinctly monotonic correlations to the Mo equivalent. With the increasing Mo equivalent, the content of the α phase decreased, while that of the β phase increased. Simultaneously, the yield strength of the Ti–Nb–Mo–Ta alloys decreased, while the strain at failure increased. Quantitative analyses were then implemented on the grain refinement strengthening, the second-phase strengthening of the α phase, and the solid solution strengthening of the Nb and Mo atoms. After comparing the separate contributions of the above determining factors, it was confirmed that the second-phase strengthening was the dominating mechanism for improving the mechanical properties of the powder metallurgic Ti–Nb–Mo–Ta alloys.

To avoid the aimless design of shaped charge liner (SCL) material for obtaining deep penetration and large penetration holes in reinforced concrete targets, new design principles are proposed in this study. Following the principles, an intermetallic-compound-reinforced Ti-17Al-29Nb alloy was prepared via hot isostatic pressing (HIP) sintering. This alloy shows high dynamic compressive strength (1583 MPa), high dynamic compressive plasticity (35 %), high elevated-temperature tensile strength (414 MPa at 800 °C), and low elevated-temperature plasticity (6 % at 800 °C). The penetrating experiments showed that the Ti-17Al-29Nb alloy liner penetrated through the 600-mm-thick C40 concrete target, forming large penetration holes. Although the penetration depth was slightly lower than that of the most commonly used pure copper liner, the diameter of the exit hole was 2.1 times that of the pure copper liner. The high jet tip velocity (7651 m/s) and large jet diameter (a maximum of 0.28 CD) were the key factors to form the high penetration depth and large penetration hole. This study not only brings a new type of SCL material with excellent penetration performance against reinforced concrete targets but also provides a new research direction for the design and selection of the SCL materials.

The synchronous detection and regulation of microRNAs (miRNAs) are essential for the early tumor diagnosis and treatment but remains a challenge. An integrative DNA tetrahedral nanomachine was self-assembled for sensitive detection and negative feedback regulation of intracellular miRNAs. This nanomachine comprised a DNA tetrahedron nanostructure as the framework, and a miRNA inhibitor-controlled allosteric DNAzyme as the core. The DNA tetrahedron brought the DNAzyme and the substrate in spatial proximity and facilitated the cellular uptake of DNAzyme. In allosteric regulation of DNAzyme, the locked tetrahedral DNAzyme (L-tetra-D) and active tetrahedral DNAzyme (A-Tetra-D) were controlled by miRNA inhibitor. The combination of miRNA inhibitor and target could trigger the conformational change from L-tetra-D to A-Tetra-D. A-Tetra-D cleaved the substrate and released fluorescence for intracellular miRNA biosensing. The DNA tetrahedral nanomachine showed excellent sensitivity (with detection limit down to 0.77 pM), specificity (with one-base mismatch discrimination), biocompatibility and stability. Simultaneously, miRNA stimulus-unlocked inhibitor introduced by our nanomachine exhibited the synchronous regulation of target cells, of which regulatory performance has been verified by the upregulated levels of downstream genes/proteins and the increased cellular apoptosis. Our study demonstrated that the DNA tetrahedral nanomachine is a promising biosense-and-treat tool for the synchronous detection and regulation of intracellular miRNA, and is expected to be applied in the early diagnosis and tailored management of cancers.

Abstract Background The topographic location of acute pontine infarction is associated with clinical syndromes and prognosis. Previous studies focused on isolated pontine infarction, but the topographic location of unisolated pontine infarction has remained unclear. Methods This was a prospective, multicenter, longitudinal registry study. Patients with acute pontine infarction confirmed by magnetic resonance imaging (MRI) were enrolled. Based on the territory of the pontine artery, the topographic location was divided into anteromedial, anterolateral, tegmental, bilateral and unilateral multiple infarctions. Results From May 1, 2003, to Oct 31, 2017, 1003 patients were enrolled, and 330 had unisolated pontine infarction. For isolated pontine infarction, 44.9, 19.8, 16.0, 13.1 and 6.2% of patients had anteromedial, anterolateral, tegmental, bilateral and unilateral multiple pontine infarctions, respectively. For unisolated pontine infarction, 30.3, 19.7, 24.5, 15.2 and 10.3% of patients had anteromedial, anterolateral, tegmental, bilateral and unilateral multiple pontine infarctions, respectively. Conclusion In this large series study, our data revealed fewer anteromedial infarctions and more tegmental and unilateral multiple infarctions in patients with unisolated pontine infarction than in patients with isolated pontine infarction.

This study aimed to explore the core knowledge topics and future research trends in neuroscience in the field of education (NIE). In this study, we have explored the diffusion of neuroscience and different neuroscience methods (e.g., electroencephalography, functional magnetic resonance imaging, eye tracking) through and within education fields. A total of 549 existing scholarly articles and 25,886 references on neuroscience in the field of education (NIE) from the Web of Science Core Collection databases were examined during the following two periods: 1995–2013 and 2014–2022. The science mapping software Vosviewer and Bibliometrix were employed for data analysis and visualization of relevant literature. Furthermore, performance analysis, collaboration network analysis, co-citation network analysis, and strategic diagram analysis were conducted to systematically sort out the core knowledge in NIE. The results showed that children and cognitive neuroscience, students and medical education, emotion and empathy, and education and brain are the core intellectual themes of current research in NIE. Curriculum reform and children’s skill development have remained central research issues in NIE, and several topics on pediatric research are emerging. The core intellectual themes of NIE revealed in this study can help scholars to better understand NIE, save research time, and explore a new research question. To the best of our knowledge, this study is one of the earliest documents to outline the NIE core intellectual themes and identify the research opportunities emerging in the field.

The Northeast Farming Region (NFR) is a major maize cropping region in China, which accounts for about 30% of national maize production. Although the regional maize production has an increasing trend in the last decades, it has greater inter-annual fluctuation. The fluctuation is caused by the increased variations of the local temperature and precipitation given the dominance of rainfed maize in the region. To secure high and stable level of maize production in the NFR under the warmer and drier future climate conditions, we employed a cross-scale model-coupling approach to identify the suitable maize cultivars and planting adaptation measures. Our simulation results show that, with proper adaptations of maize cultivars and adjustments of planting/harvest dates, both maize planting area and yield per unit of land will increase in most regions of NFR. This finding indicates that proactive adaptation can help local farmers to reap the benefits of increasing heat resource brought in by global warming, thus avoiding maize production losses as reported in other studies. This research can potentially contribute to the development of agricultural climate services to support climate-smart decisions for agricultural adaptations at the plot, farm and regional scales, in terms of planning the planting structure of multiple crops, breeding suitable maize varieties, and optimizing planting and field management schedules.

Flame monitoring of industrial combustors with high-reliability sensors is essential to operation security and performance. An ion current flame sensor with a simple structure has great potential to be widely used, but a weak ion current is the critical defect to its reliability. In this study, parameters of the ion current sensor used for monitoring flames on a Bunsen burner are suggested, and a method of further improving the ion current is proposed. Effects of the parameters, including the excitation voltage, electrode area, and electrode radial and vertical positions on the ion current, were investigated. The ion current grew linearly with the excitation voltage. Given that the electrodes were in contact with the flame fronts, the ion current increased with the contact area of the cathode but independent of the contact area of the anode. The smaller electrode radial position resulted in a higher ion current. The ion current was insensitive to the anode vertical position but largely sensitive to the cathode vertical position. Based on the above ion current regularities, the sensor parameters were suggested as follows: The burner served as a cathode and the platinum wire acted as an anode. The excitation voltage, anode radial and vertical positions were 120 V, 0 mm, and 6 mm, respectively. The method of further improving the ion current by adding multiple sheet cathodes near the burner exit was proposed and verified. The results show that the ion current sensor with the suggested parameters could correctly identify the flame state, including the ignition, combustion, and extinction, and the proposed method could significantly improve the magnitude of the ion current.

The treatment of wound inflammation is intricately linked to the concentration of reactive oxygen species (ROS) in the wound microenvironment. Among these ROS, H2O2 serves as a critical signaling molecule and second messenger, necessitating the urgent need for its rapid real-time quantitative detection, as well as effective clearance, in the pursuit of effective wound inflammation treatment. Here, we exploited a sophisticated 3D Cu2-xSe/GO nanostructurebased nanonzymatic H2O2 electrochemical sensor, which is further decorated with evenly distributed Pt nanoparticles (Pt NPs) through electrodeposition. The obtained Cu2-xSe/GO@Pt/SPCE sensing electrode possesses a remarkable increase in specific surface derived from the three-dimensional surface constructed by GO nanosheets. Moreover, the localized surface plasma effect of the Cu2-xSe nanospheres enhances the separation of photogenerated electron-hole pairs between the interface of the Cu2-xSe NPs and the Pt NPs. This innovation enables near-infrared light-enhanced catalysis, significantly reducing the detection limit of the Cu2-xSe/GO@Pt/SPCE sensing electrode for H2O2 (from 1.45 mM to 0.53mM) under NIR light. Furthermore, this biosensor electrode enables in-situ real-time monitoring of H2O2 released by cells. The NIR-enhanced Cu2-xSe/GO@Pt/SPCE sensing electrode provide a simple-yeteffective method to achieve a detection of ROS (H2O2-OH) with high sensitivity and efficiency. This innovation promises to revolutionize the field of wound inflammation treatment by providing clinicians with a powerful tool for accurate and rapid assessment of ROS levels, ultimately leading to improved patient outcomes. [ABSTRACT FROM AUTHOR]

Coastal regions have experienced significant environmental changes and increased vulnerability to floods caused by the combined effect of multiple flood drivers such as storm surge, heavy rainfall, and river discharge, i.e., compound floods. Hence, for a sustainable development of coastal cities, it is necessary to understand the spatiotemporal dynamics and future trends of compound flood hazard. While the statistical dependence between flood drivers, i.e., rainfall and storm surges, has been extensively studied, the sensitivity of the inundated areas to the relative timing of driver's individual peaks is less understood and location dependent. To fill this gap, here we propose a framework combining a statistical dependence model for compound event definition and a hydrodynamic model to assess inundation maps of compound flooding from storm surge and rainfall during typhoon season in Shanghai. First, we determine the severity of the joint design event, i.e., peak surge and precipitation, based on the copula model. Second, we use the Same Frequency Amplification (SFA) method to transform the design event values in hourly timeseries so that they represent boundary conditions to force hydrodynamic models. Third, we assess the sensitivity of inundation maps to the time lag between storm surge peak and rainfall. Finally, we define flood zones based on the primary flood driver and we delineate flood zones under the worst compound flood scenario. The study highlights that the temporal delay between storm surge and rainfall plays a pivotal role in shaping the dynamics of flooding events. More specifically, the worst conditions in terms of cumulative inundation depth occur when rainfall precedes the storm surge peak. At the same time, the results show that in Shanghai surge is the primary flood driver. High storm surge at the eastern part of the city (Wusongkou tidal gauge) propagate upstream in the Huangpu River resulting in fluvial flooding in Shanghai city center and several surrounding districts. This calls for a better fluvial flooding control system hinging on the backwater effect during high surge in the upper and middle Huangpu River and in the newly added urbanized areas to ensure flood resilience. The proposed framework is useful to evaluate and predict flood hazard in coastal cities, and the results can provide guidance for urban disaster prevention and mitigation. [ABSTRACT FROM AUTHOR]