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Abstract Objective Although some studies have linked smoking to mortality after out-of-hospital cardiac arrests (OHCAs), data regarding smoking and mortality after OHCAs have not yet been discussed in a meta-analysis. Thus, this study conducted this systematic review to clarify the association. Methods The study searched Medline-PubMed, Web of Science, Embase and Cochrane libraries between January 1972 and July 2022 for studies that evaluated the association between smoking and mortality after OHCAs. Studies that reportedly showed relative risk estimates with 95% confidence intervals (CIs) were included. Results Incorporating a collective of five studies comprising 2477 participants, the analysis revealed a lower mortality risk among smokers in the aftermath of OHCAs compared with non-smokers (odds ratio: 0.77; 95% CI 0.61–0.96; P

Abstract Background To assess the feasibility and tissue response of using a gold nanoparticle (AuNP)-integrated silicone-covered self-expandable metal stent (SEMS) for local hyperthermia in a rat esophageal model. Methods The study involved 42 Sprague–Dawley rats. Initially, 6 animals were subjected to near-infrared (NIR) laser irradiation (power output from 0.2 to 2.4 W) to assess the in vitro heating characteristics of the AuNP-integrated SEMS immediately after its placement. The surface temperature of the stented esophagus was then measured using an infrared thermal camera before euthanizing the animals. Subsequently, the remaining 36 animals were randomly divided into 4 groups of 9 each. Groups A and B received AuNP-integrated SEMS, while groups C and D received conventional SEMS. On day 14, groups A and C underwent NIR laser irradiation at a power output of 1.6 W for 2 min. By days 15 (3 animals per group) or 28 (6 animals per group), all groups were euthanized for gross, histological, and immunohistochemical analysis. Results Under NIR laser irradiation, the surface temperature of the stented esophagus quickly increased to a steady-state level. The surface temperature of the stented esophagus increased proportionally with power outputs, being 47.3 ± 1.4 °C (mean ± standard deviation) at 1.6 W. Only group A attained full circumferential heating through all layers, from the epithelium to the muscularis propria, demonstrating marked apoptosis in these layers without noticeable necroptosis. Conclusions Local hyperthermia using the AuNP-integrated silicone-covered SEMS was feasible and induced cell death through apoptosis in a rat esophageal model. Relevance statement A gold nanoparticle-integrated silicone-covered self-expanding metal stent has been developed to mediate local hyperthermia. This approach holds potential for irreversibly damaging cancer cells, improving the sensitivity of cancer cells to therapies, and triggering systemic anticancer immune responses. Key points • A gold nanoparticle-integrated silicone-covered self-expanding metal stent was placed in the rat esophagus. • Upon near-infrared laser irradiation, this stent quickly increased the temperature of the stented esophagus. • Local hyperthermia using this stent was feasible and resulted in cell death through apoptosis. Graphical Abstract

Abstract Background The efficacy of coronavirus disease 2019 (COVID‐19) vaccines in preventing SARS‐CoV‐2 infection in patients with hepatocellular carcinoma (HCC) is not clear. Methods From January 2022 to October 2022, patients diagnosed with HCC in a prospective, multicenter, observational cohort were analyzed. Results One hundred and forty‐one patients with (n = 107) or without COVID‐19 vaccination (n = 34) were included. The number of patients with severe or very severe infection was relatively lower in the vaccinated group (3.7% vs. 11.8%, p = 0.096). Median infection‐free survival in the vaccinated group (14.0 vs. 8.3 months, p = 0.010) was significantly longer than that in the unvaccinated group. COVID‐19 vaccination (hazard ratio (HR) HR = 0.47), European Cooperative Oncology Group performance score = 0 (HR = 2.06), and extrahepatic spread (HR = 0.28) were found to be the independent predictive factors for infection‐free survival. Conclusion COVID‐19 vaccines could effectively reduce the SARS‐Cov‐2 infection in patients with HCC.

ObjectivesCerebral small vessel disease (CSVD) visible on MRI can be asymptomatic. We sought to develop and validate a model for detecting CSVD in rural older adults.MethodsThis study included 1,192 participants in the MRI sub-study within the Multidomain Interventions to Delay Dementia and Disability in Rural China. Total sample was randomly divided into training set and validation set. MRI markers of CSVD were assessed following the international criteria, and total CSVD burden was assessed on a scale from 0 to 4. Logistic regression analyses were used to screen risk factors and develop the diagnostic model. A nomogram was used to visualize the model. Model performance was assessed using the area under the receiver-operating characteristic curve (AUC), calibration plot, and decision curve analysis.ResultsThe model included age, high blood pressure, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), and history of cerebral infarction. The AUC was 0.71 (95% CI, 0.67–0.76) in the training set and 0.69 (95% CI, 0.63–0.76) in the validation set. The model showed high coherence between predicted and observed probabilities in both the training and validation sets. The model had higher net benefits than the strategy assuming all participants either at high risk or low risk of CSVD for probability thresholds ranging 50–90% in the training set, and 65–98% in the validation set.ConclusionA model that integrates routine clinical factors could detect CSVD in older adults, with good discrimination and calibration. The model has implication for clinical decision-making.

BackgroundNonalcoholic fatty liver disease (NAFLD), also known as metabolic associated fatty liver disease (MAFLD), is a common liver condition characterized by excessive fat accumulation in the liver which is not caused by alcohol. The main causes of NAFLD are obesity and insulin resistance. Dachaihu decoction (DCHD), a classic formula in traditional Chinese medicine, has been proved to treat NAFLD by targeting different aspects of pathogenesis and is being progressively used in the treatment of NAFLD. DCHD is commonly applied in a modified form to treat the NAFLD. In light of this, it is imperative to conduct a systematic review and meta-analysis to assess the effectiveness and safety of DCHD in the management of NAFLD. There is a need for a systematic review and meta-analysis to assess the effectiveness and safety of modified DCHD in treating NAFLD.ObjectiveThe objective of this meta-analysis was to systematically assess the clinical effectiveness and safety of DCHD in treating NAFLD.MethodsThis meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Including seven databases, both Chinese and English databases were searched for relevant studies. The quality of included studies was carefully assessed using the bias risk assessment tool in the Cochrane Handbook. Eligible articles were the source of extracted data which was meta-analyzed by using Review Manager 5.4 and Stata 17.0.ResultsA total of 10 studies containing 825 patients were included. Compared with conventional treatments, combined treatment could clearly improve the liver function of NAFLD patients, which could reduce the levels of ALT (MD = −7.69 U/L, 95% CI: −11.88 to −3.51, p

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Incomplete assembly could affect product quality and performance, and even cause inestimable losses. In the industrial environment, the lack of image datasets and the inability to obtain the physical assembly in advance is a challenge for machine vision to detect assembly integrity. We propose a 3D CAD model-based method to detect assembly integrity without physical assembly. 3D CAD models are utilized for 2D image rendering and dataset construction, and automatic labeling can be achieved through edge extraction and minimum enclosing rectangle fitting rather than by hand. An end-to-end detection neural network based on Faster-RCNN is trained in the datasets. The VGG network as detection neural network to extract features, and the generated feature map determines the candidate detection region through RPN. Fast-RCNN then detects the object in the image. Finally, by detecting images from multiple views with dimension reduction and comparing them with prior knowledge, we can judge whether there are missing parts in the assembly. Experimental results show that the network model can accurately detect the integrity of the assembly, and the average accuracy (mAP) reaches 88.9%. The method can also provide theoretical guidance for future physical assembly and shorten the experimental process.

Abstract The human oral microbiome harbors one of the most diverse microbial communities in the human body, playing critical roles in oral and systemic health. Recent technological innovations are propelling the characterization and manipulation of oral microbiota. High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes. New long-read platforms improve genome assembly from complex samples. Single-cell genomics provides insights into uncultured taxa. Advanced imaging modalities including fluorescence, mass spectrometry, and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution. Fluorescence techniques link phylogenetic identity with localization. Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification. Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches. Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly, gene expression, metabolites, microenvironments, virulence mechanisms, and microbe-host interfaces in the context of health and disease. However, significant knowledge gaps persist regarding community origins, developmental trajectories, homeostasis versus dysbiosis triggers, functional biomarkers, and strategies to deliberately reshape the oral microbiome for therapeutic benefit. The convergence of sequencing, imaging, cultureomics, synthetic systems, and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict, prevent, diagnose, and treat associated oral diseases.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

IntroductionSoybeans are an important crop used for food, oil, and feed. However, China’s soybean self-sufficiency is highly inadequate, with an annual import volume exceeding 80%. RGB cameras serve as powerful tools for estimating crop yield, and machine learning is a practical method based on various features, providing improved yield predictions. However, selecting different input parameters and models, specifically optimal features and model effects, significantly influences soybean yield prediction.MethodsThis study used an RGB camera to capture soybean canopy images from both the side and top perspectives during the R6 stage (pod filling stage) for 240 soybean varieties (a natural population formed by four provinces in China: Sichuan, Yunnan, Chongqing, and Guizhou). From these images, the morphological, color, and textural features of the soybeans were extracted. Subsequently, feature selection was performed on the image parameters using a Pearson correlation coefficient threshold ≥0.5. Five machine learning methods, namely, CatBoost, LightGBM, RF, GBDT, and MLP, were employed to establish soybean yield estimation models based on the individual and combined image parameters from the two perspectives extracted from RGB images.Results(1) GBDT is the optimal model for predicting soybean yield, with a test set R2 value of 0.82, an RMSE of 1.99 g/plant, and an MAE of 3.12%. (2) The fusion of multiangle and multitype indicators is conducive to improving soybean yield prediction accuracy.ConclusionTherefore, this combination of parameters extracted from RGB images via machine learning has great potential for estimating soybean yield, providing a theoretical basis and technical support for accelerating the soybean breeding process.

In the rapidly evolving landscape of transportation infrastructure, the quality and condition of road networks play a pivotal role in societal progress and economic growth. In the realm of road distress detection, traditional methods have long grappled with manual intervention and high costs, requiring trained observers for time-consuming and expensive data collection processes. The limitations of these approaches are compounded by challenges in adapting to diverse road surfaces and handling low-resolution data, particularly in early automated distress survey technologies. This article addresses the critical need for efficient road distress detection, a key component of ensuring safe and reliable transportation systems. Effectively addressing these challenges is crucial for enhancing the efficiency, accuracy, and safety of road distress detection systems. Leveraging advancements in object detection, we introduce the Innovative Road Distress Detection (IR-DD), a novel framework that integrates the YOLOv8 algorithm to enhance the accuracy and real-time capabilities of road distress detection, catering to applications such as smart cities and autonomous vehicles. Our approach incorporates bidirectional feature pyramid network (BiFPN) recursive feature fusion and bidirectional connections to optimize the utilization of multi-scale features, addressing challenges related to information loss and gradients encountered in traditional methods. Comprehensive experimental analysis demonstrates the superior performance, efficiency, and robustness of our integrated approach, positioning it as a cost-effective and compelling alternative to conventional road distress detection methods. Our findings demonstrate the superior performance of our approach compared to other state-of-the-art methods across various evaluation metrics, including precision, recall, F1 score, and mean average precision (mAP) at different intersection over union (IoU) thresholds. Specifically, our method achieves notable results with a precision of 0.666, F1 score of 0.630, mAP@0.5 of 0.650, all while operating at a speed of 86 frames per second (FPS). These outcomes underscore the effectiveness of our approach in real-time road distress detection. This article contributes to the ongoing innovation in object detection techniques, emphasizing the practicality and effectiveness of our proposed solution in advancing the field of road distress detection.

BackgroundParkinson’s disease (PD) is characterized by a range of motor symptoms as well as documented sensory dysfunction. This sensory dysfunction can present itself either as a “pure” sensory disturbance or as a consequence of sensory-motor integration within the central nervous system. This study aims to investigate changes in the functional connectivity of the primary somatosensory cortex (S1) and its clinical significance in Parkinson’s disease (PD), an area that has received limited attention in previous neuroimaging studies.MethodsThis study included thirty-three patients with PD and thirty-four healthy controls (HCs). Clinical evaluations were conducted to assess the clinical manifestations, severity, and functional capacity of all the patients. Resting-state functional MRI (fMRI) was employed to evaluate the functional connectivity of six paired S1 subregions in the participants. Seed-based correlation (SBC) analysis was utilized to construct the correlation matrix among the subregions and to generate connectivity maps between the subregions and the remaining brain voxels. Finally, the study employed partial least-squares (PLS) correlation analysis to investigate the association between modified functional connectivity and clinical characteristics in PD patients.ResultsIn the correlation matrix, patients with PD demonstrated a notable decrease in functional connectivity across various S1 subregions in comparison to HCs (p

Tool condition monitoring technology is an indispensable part of intelligent manufacturing. Most current research focuses on complex signal processing techniques or advanced deep learning algorithms to improve prediction performance without fully leveraging the end-to-end advantages of deep learning. The challenge lies in transforming multi-sensor raw data into input data suitable for direct model feeding, all while minimizing data scale and preserving sufficient temporal interpretation of tool wear. However, there is no clear reference standard for this so far. In light of this, this paper innovatively explores the processing methods that transform raw data into input data for deep learning models, a process known as an input paradigm. This paper introduces three new input paradigms: the downsampling paradigm, the periodic paradigm, and the subsequence paradigm. Then an improved hybrid model that combines a convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM) was employed to validate the model’s performance. The subsequence paradigm demonstrated considerable superiority in prediction results based on the PHM2010 dataset, as the newly generated time series maintained the integrity of the raw data. Further investigation revealed that, with 120 subsequences and the temporal indicator being the maximum value, the model’s mean absolute error (MAE) and root mean square error (RMSE) were the lowest after threefold cross-validation, outperforming several classical and contemporary methods. The methods explored in this paper provide references for designing input data for deep learning models, helping to enhance the end-to-end potential of deep learning models, and promoting the industrial deployment and practical application of tool condition monitoring systems.

In an experiment performed on the Shenguang-III prototype laser facility, collective Thomson scattering (TS) is used to study the spatial growth of stimulated Brillouin scattering (SBS) in a gas-filled hohlraum by detecting the SBS-driven ion acoustic wave. High-quality time-resolved SBS and TS spectra are obtained simultaneously in the experiment, and these are analyzed by a steady-state code based on the ray-tracing model. The analysis indicates that ion–ion collisions may play an important role in suppressing SBS growth in the Au plasma; as a result, the SBS excited in the filled gas region is dominant. In the early phase of the laser pulse, SBS originates primarily from the high-density plasma at the edges of the interaction beam channel, which is piled up by the heating of the interaction beam. Throughout the duration of the laser pulse, the presence of the TS probe beam might mitigate SBS by perturbing the density distribution around the region overlapping with the interaction beam.

Objective: The study aimed to investigate changes in basal levels of the inhibitory γ-aminobutyric acid (GABA) neurotransmitter in the sensorimotor cortex (SMC) and cortical gyrification in patients with Parkinson’s disease (PD), which could further identify potential imaging biomarkers for PD, particularly in patients with early-onset Parkinson’s disease (EOPD). Method: Fifty patients with PD (EOPD: 10, late-onset Parkinson’s disease [LOPD]: 40) and fifty-two age- and gender-matched healthy controls (HC) underwent GABA-edited 1H MRS of the SMC and high-resolution 3D T1-weighted brain imaging. GABA levels and local gyrification index (LGI) were calculated to assess GABAergic and cortical gyrification deficits in PD. Result: The Pearson correlation coefficients revealed significant negative associations between eight indicators, including GABA/Cr level and local gyrification index (LGI) of specific cortical regions (precentral, postcentral, entorhinal, superiortemporal, posteriorcingulate, cuneus, and transversetemporal cortex), and the likelihood of Parkinson’s disease (r

IntroductionThe FIFA World Cup is not only the most lucrative athletic event globally, but it also functions as a platform for promoting peace owing to FIFA's new vision. Nevertheless, the determinants of TV viewership ratings, especially in the Chinese market, which is a critical revenue stream for FIFA TV broadcasting, are still unsolved. Using a distributional regression, this study aimed to quantify the dynamics of viewership ratings for the FIFA World Cup 2022 in mainland China.MethodsThe CCTV viewership ratings were modeled using 12 covariables related to Chinese TV consumer behavior. Given the data structure, a Logit Normal regression model was chosen to fit the location and dispersion parameters of viewership ratings to explanatory variables.ResultsIn the fitted heteroscedastic model, the viewership ratings dynamics in mainland China were driven by the match kick-off time: μ^=logistic[−4.874+0.043×matchkick-offtime]. In addition, the model captures the factors that influence the variations in viewership ratings: σ^=exp[−14.26–1.346 (if, FIFA World Cup champion = “Yes”) + 0.004 × FIFA world ranking]. Thus, it shows that the FIFA World Cup champions tamp down such variations, leading to a more stable viewing behavior among Chinese consumers.ConclusionsTime- and team-sensitive strategies are proposed to aid in crafting uncertainty-suppressing business decisions for the FIFA World Cup 2026. Ultimately, in the more insecure 2020s, a broader live coverage of the FIFA World Cup would be invaluable for promoting peace.

Introduction: Small-scaled robotic walkers play an increasingly important role in Activity of Daily Living (ADL) assistance in the face of ever-increasing rehab requirements and existing equipment drawbacks. This paper proposes a Rehabilitation Robotic Walker (RRW) for walking assistance and body weight support (BWS) during gait rehabilitation.Methods: The walker provides the patients with weight offloading and guiding force to mimic a series of the physiotherapist’s (PT’s) movements, and creates a natural, comfortable, and safe environment. This system consists of an omnidirectional mobile platform, a BWS mechanism, and a pelvic brace to smooth the motions of the pelvis. To recognize the human intentions, four force sensors, two joysticks, and one depth-sensing camera were used to monitor the human-machine information, and a multimodal fusion algorithm for intention recognition was proposed to improve the accuracy. Then the system obtained the heading angle E, the pelvic pose F, and the motion vector H via the camera, the force sensors, and the joysticks respectively, classified the intentions with feature extraction and information fusion, and finally outputted the motor speed control through the robot’s kinematics.Results: To validate the validity of the algorithm above, a preliminary test with three volunteers was conducted to study the motion control. The results showed that the average error of the integral square error (ISE) was 2.90 and the minimum error was 1.96.Discussion: The results demonstrated the efficiency of the proposed method, and that the system is capable of providing walking assistance.

Spot segregation and banded defect are unsolved technical problems of high-quality steel. In this paper, spot segregation of different sizes and irregular morphology were found in equiaxed crystal zones of slab. The characteristics of speckle type and porosity type spot segregation were compared, where the segregation degree of large-size spot segregation was worse. After heat treatment and hot rolling processes, the concentration changes of carbon, manganese, and iron were obtained by EPMA and SEM-EDS. The results showed that the carbon distribution became more even but the change in manganese concentration was not obvious, and the maximum concentration of carbon was almost unchanged, which indicated that severe segregation cannot be alleviated by the existing processes. Circular and irregular atoms were found in the banded defect. These atoms cooperate with thermodynamic coupling caused by hot rolling and contribute to the composition homogenization and void healing of the banded defect. In addition, the connection between holding time and diffusion efficiency was studied by simulating the uphill diffusion process of carbon and manganese at a holding temperature of 1250 °C. When the diameter of the spot segregation was less than 3000 μm, the carbon could uniformly diffuse before 12,000 s, and then if the spot segregation was kept warm for 36,000 s, the mean concentration of manganese was still less than 1.0 wt%, which is too high to be considered homogenized. Finally, an evolution model was established to explain the formation process and evolution mechanism from spot segregation to band defect.

Abstract The biosynthetic process of selenium nanoparticles (SeNPs) by specific bacterial strain, whose growth directly affects the synthesis efficiency, has attracted great attentions. We previously reported that Bacillus paralicheniformis SR14, a SeNPs-producing bacteria, could improve intestinal antioxidative function in vitro. To further analyze the biological characteristics of SR14, whole genome sequencing was used to reveal the genetic characteristics in selenite reduction and sugar utilization. The results reviewed that the genome size of SR14 was 4,448,062 bp, with a GC content of 45.95%. A total of 4300 genes into 49 biological pathways was annotated to the KEGG database. EC: 1.1.1.49 (glucose-6-phosphate 1-dehydrogenase) and EC: 5.3.1.9 (glucose-6-phosphate isomerase), were found to play a potential role in glucose degradation and EC:2.7.1.4 (fructokinase) might be involved in the fructose metabolism. Growth profile and selenite-reducing ability of SR14 under different sugar supplements were determined and the results reviewed that glucose had a better promoting effect on the reduction of selenite and growth of bacteria than fructose, sucrose, and maltose. Moreover, RT-qPCR experiment proved that glucose supplement remarkably promoted the expressions of thioredoxin, fumarate reductase, and the glutathione peroxidase in SR14. Analysis of mRNA expression showed levels of glucose-6-phosphate dehydrogenase and fructokinase significantly upregulated under the supplement of glucose. Overall, our data demonstrated the genomic characteristics of SR14 and preliminarily determined that glucose supplement was most beneficial for strain growth and SeNPs synthesis.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

Abstract Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances in nanotechnology, accompanied by our growing understanding of cancer biology and nano-bio interactions, have led to the development of a series of nanocarriers, which aim to improve the therapeutic efficacy while reducing off-target toxicity of the encapsulated anticancer agents through tumor tissue-, cell-, or organelle-specific targeting. However, the vast majority of nanocarriers do not possess hierarchical targeting capability, and their therapeutic indices are often compromised by either poor tumor accumulation, inefficient cellular internalization, or inaccurate subcellular localization. This Review outlines current and prospective strategies in the design of tumor tissue-, cell-, and organelle-targeted cancer nanomedicines, and highlights the latest progress in hierarchical targeting technologies that can dynamically integrate these three different stages of static tumor targeting to maximize therapeutic outcomes. Finally, we briefly discuss the current challenges and future opportunities for the clinical translation of cancer nanomedicines.

Implantable drug delivery systems formed upon injection offer a host of advantages, including localized drug administration, sustained release, minimized side effects, and enhanced patient compliance. Among the various techniques utilized for the development of in situ forming drug implants, solvent-induced phase inversion emerges as a particularly promising approach. However, synthetic polymer-based implants have been associated with undesirable effects arising from polymer degradation. In response to this challenge, a novel category of drug delivery systems, known as phospholipids-based phase separation gels (PPSGs), has emerged. These gels, characterized by their low initial viscosity, exhibit injectability and undergo rapid transformation into in situ implants when exposed to an aqueous environment. A typical PPSG formulation comprises biodegradable components, such as phospholipids, pharmaceutical oil, and a minimal amount of ethanol. The minimized organic solvents in the composition show good biocompatibility. And the relatively simple composition holds promise for industrial-scale manufacturing. This comprehensive review provides an overview of the principles and advancements in PPSG systems, with specific emphasis on their suitability as drug delivery systems for a wide range of active pharmaceutical ingredients (APIs), spanning from small molecules to peptides and proteins. Additionally, we explore the critical parameters and underlying principles governing the formulation of PPSG-based drug delivery strategies, offering valuable insights on optimization strategies.

Grasping robots always confront challenges such as uncertainties in object size, orientation, and type, necessitating effective feature augmentation to improve grasping detection performance. However, many prior studies inadequately emphasize grasp-related features, resulting in suboptimal grasping performance. To address this limitation, this paper proposes a new grasping approach termed the Feature-Augmented Grasp Detection Network (FAGD-Net). The proposed network incorporates two modules designed to enhance spatial information features and multi-scale features. Firstly, we introduce the Residual Efficient Multi-Scale Attention (Res-EMA) module, which effectively adjusts the importance of feature channels while preserving precise spatial information within those channels. Additionally, we present a Feature Fusion Pyramidal Module (FFPM) that serves as an intermediary between the encoder and decoder, effectively addressing potential oversights or losses of grasp-related features as the encoder network deepens. As a result, FAGD-Net achieved advanced levels of grasping accuracy, with 98.9% and 96.5% on the Cornell and Jacquard datasets, respectively. The grasp detection model was deployed on a physical robot for real-world grasping experiments, where we conducted a series of trials in diverse scenarios. In these experiments, we randomly selected various unknown household items and adversarial objects. Remarkably, we achieved high success rates, with a 95.0% success rate for single-object household items, 93.3% for multi-object scenarios, and 91.0% for cluttered scenes.

In order to rapidly breed high-quality varieties, an increasing number of plant researchers have identified the functions of a large number of genes, but there is a serious lack of research on plants’ phenotypic traits. This severely hampers the breeding process and exacerbates the dual challenges of scarce resources and resource development and utilization. Currently, research on crop phenotyping has gradually transitioned from traditional methods to HTP technologies, highlighting the high regard scientists have for these technologies. It is well known that different crops’ phenotypic traits exhibit certain differences. Therefore, in rapidly acquiring phenotypic data and efficiently extracting key information from massive datasets is precisely where HTP technologies play a crucial role in agricultural development. The core content of this article, starting from the perspective of crop phenomics, summarizes the current research status of HTP technology, both domestically and internationally; the application of HTP technology in above-ground and underground parts of crops; and its integration with precision agriculture implementation and multi-omics research. Finally, the bottleneck and countermeasures of HTP technology in the current agricultural context are proposed in order to provide a new method for phenotype research. HTP technologies dynamically monitor plant growth conditions with multi-scale, comprehensive, and automated assessments. This enables a more effective exploration of the intrinsic “genotype-phenotype-environment” relationships, unveiling the mechanisms behind specific biological traits. In doing so, these technologies support the improvement and evolution of superior varieties.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Abstract Background Intramuscular fat (IMF) content is a critical indicator of pork quality, and abnormal IMF is also relevant to human disease as well as aging. Although N6-methyladenosine (m6A) RNA modification was recently found to regulate adipogenesis in porcine intramuscular fat, however, the underlying molecular mechanisms was still unclear. Results In this work, we collected 20 longissimus dorsi muscle samples with high (average 3.95%) or low IMF content (average 1.22%) from a unique heterogenous swine population for m6A sequencing (m6A-seq). We discovered 70 genes show both differential RNA expression and m6A modification from high and low IMF group, including ADIPOQ and SFRP1, two hub genes inferred through gene co-expression analysis. Particularly, we observed ADIPOQ, which contains three m6A modification sites within 3′ untranslated and protein coding region, could promote porcine intramuscular preadipocyte differentiation in an m6A-dependent manner. Furthermore, we found the YT521‑B homology domain family protein 1 (YTHDF1) could target and promote ADIPOQ mRNA translation. Conclusions Our study provided a comprehensive profiling of m6A methylation in porcine longissimus dorsi muscle and characterized the involvement of m6A epigenetic modification in the regulation of ADIPOQ mRNA on IMF deposition through an m6A-YTHDF1-dependent manner.

ABSTRACTBackground Dental caries is a chronic, multifactorial and biofilm-mediated oral bacterial infection affecting almost every age group and every geographical region. Streptococcus mutans is considered an important pathogen responsible for the initiation and development of dental caries. It produces exopolysaccharides in situ to promote the colonization of cariogenic bacteria and coordinate dental biofilm development.Objective The understanding of the regulatory mechanism of S. mutans biofilm formation can provide a theoretical basis for the prevention and treatment of caries.Design At present, an increasing number of studies have identified many regulatory systems in S. mutans that regulate biofilm formation, including second messengers (e.g. c-di-AMP, Ap4A), transcription factors (e.g. EpsR, RcrR, StsR, AhrC, FruR), two-component systems (e.g. CovR, VicR), small RNA (including sRNA0426, srn92532, and srn133489), acetylation modifications (e.g. ActG), CRISPR-associated proteins (e.g. Cas3), PTS systems (e.g. EIIAB), quorum-sensing signaling system (e.g. LuxS), enzymes (including Dex, YidC, CopZ, EzrA, lmrB, SprV, RecA, PdxR, MurI) and small-molecule metabolites.Results This review summarizes the recent progress in the molecular regulatory mechanisms of exopolysaccharides synthesis and biofilm formation in S. mutans.

The concept of sepsis has recently evolved from one of a ‘systemic inflammatory response syndrome caused by infection’ to a ‘severe, potentially fatal organic dysfunction caused by an inadequate or imbalanced host response to infection’. Organ dysfunction is closely related to sepsis. Multiple organ dysfunction syndrome (MODS) is the most serious outcome of sepsis, often leading to a poor prognosis. However, specific drugs for sepsis and MODS caused by sepsis remain undetermined, and the fatality rate is relatively high. Under the guidance of modern medicine, traditional Chinese medicine (TCM) has gained a wealth of experience in the prevention and treatment of sepsis and plays a key role via the effects of its numerous components, pathways and targets. This study used ‘Sepsis’, ‘Organ dysfunction’ and ‘Traditional Chinese medicine’ as strategies for searching the databases of Chinese National Knowledge Infrastructure, Wanfang, PubMed and The Web of Science. This paper presents an overview of the current status of TCM component formulations for preventing and treating sepsis with MODS to provide a theoretical basis for clinical treatment and drug development.

Background As a three-dimensional network involving glycosaminoglycans (GAGs), proteoglycans (PGs) and other glycoproteins, the role of extracellular matrix (ECM) in tumorigenesis is well revealed. Abnormal glycosylation in liver cancer is correlated with tumorigenesis and chemoresistance. However, the role of galactosyltransferase in HCC (hepatocellular carcinoma) is largely unknown. Methods Here, the oncogenic functions of B4GALT7 (beta-1,4-galactosyltransferase 7) were identified in HCC by a panel of in vitro experiments, including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, transwell and flow cytometry assay. The expression of B4GALT7 in HCC cell lines and tissues were examined by qPCR (real-time quantitative polymerase chain reaction) and western blot assay. The binding between B4GALT7 and miR-338-3p was examined by dual-luciferase reporter assay. Results B4GALT7 encodes galactosyltransferase I and it is highly expressed in HCC cells and human HCC tissues compared with para-tumor specimens. MiR-338-3p was identified to bind the 3′ UTR (untranslated region) of B4GALT7. Highly expressed miR-338-3p suppressed HCC cell invasive abilities and rescued the tumor-promoting effect of B4GALT7 in HCC. ShRNA (short hairpin RNA) mediated B4GALT7 suppression reduced HCC cell invasive abilities, and inhibited the expression of MMP-2 and Erk signaling. Conclusion These findings identified B4GALT7 as a potential prognostic biomarker and therapeutic target for HCC.

Probiotics can improve animal growth performance and intestinal health. Bacillus species, Lactobacillus species, Bifidobacterium species, yeast etc. are the common types of probiotics. However, understanding the effects of probiotics on the immune status and gut microbiota of weaning piglets and how the probiotics exert their impact are still limited. This study aimed to investigate the effects of Bacillus amyloliquefaciens 40 (BA40) on the performance, immune status and gut microbiota of piglets. A total of 12 litters of newborn piglets were randomly divided into 3 groups. Piglets in control group were orally dosed with phosphate buffered saline; BA40 group and probiotics group were orally gavaged with resuspension BA40 and a probiotics product, respectively. The results showed that BA40 treatment significantly decreased (P

Laser trackers are instruments used to measure the three-dimensional coordinates of objects with high precision. It is necessary to study calibration methods to identify geometric errors of laser trackers so as to compensate for errors and improve measurement accuracy. Among the offsets, tilts, and eccentricity errors in the system, the transit tilt and offset errors play important roles and have an essential effect on the measurement accuracy, which need to be calibrated and compensated for. Current methods for detecting geometric errors between the transit and standing axes are complex and time-consuming. In this paper, a fast and novel calibration method is proposed, which can be easily operated with high precision. Two test rods are coaxially mounted on the ends of the transit axis to extend the hidden transit axis. Then, a telecentric measurement system is used to record the projection images of the test rods and identify the position of the transit axis. The transit offset and tilt errors were thus obtained by comparing the central axis positions of the two test rods before and after the standing axis rotated 180 degrees. Moreover, a numerical analysis method was proposed based on the least square circle fitting method to calibrate the installation eccentricity errors of the test rods. Experimental results verify that the measurement accuracy of the laser tracker can be improved after error compensation using the calibrated transit offset and tilt errors. The measurement error of the laser tracker can be reduced from 161 µm to about 73 µm after compensation at a distance of 5 m, while the error can be decreased from 143 µm to about 108 µm at a distance of 10 m.

The first laser–plasma interaction experiment using lasers of eight beams grouped into one octad has been conducted on the Shenguang Octopus facility. Although each beam intensity is below its individual threshold for stimulated Brillouin backscattering (SBS), collective behaviors are excited to enhance the octad SBS. In particular, when two-color/cone lasers with wavelength separation 0.3 nm are used, the backward SBS reflectivities show novel behavior in which beams of longer wavelength achieve higher SBS gain. This property of SBS can be attributed to the rotation of the wave vectors of common ion acoustic waves due to the competition of detunings between geometrical angle and wavelength separation. This mechanism is confirmed using massively parallel supercomputer simulations with the three-dimensional laser–plasma interaction code LAP3D.

BackgroundIn this study, we aimed to explore the antihypertensive effect of 23 and 52% concentrations of low-sodium salt combined with the Chinese Modified Dietary Approaches to Stop Hypertension (CM-DASH) diet in patients with hypertension and type 2 diabetes.MethodsWe conducted a randomized controlled single-blind trial with a semi-open design. One hundred and thirty-two participants were randomly assigned into Group A (control group), Group B (52% low-sodium salt group), Group C (23% low-sodium salt group), and Group D (meal pack group) for 8 weeks of dietary intervention. All participants were followed weekly to collect data on blood pressure, salt use, and adverse events. Blood and 24-h urine samples were analyzed at baseline, 4 weeks, and the end of the intervention.ResultsAt the end of the intervention, the mean blood pressure decreased significantly by 10.81/5.03 mmHg, 14.32/6.32 mmHg, 14.20/6.59 mmHg, and 19.06/7.82 mmHg in Groups A–D, respectively, compared with baseline (p

Background Chronic stress promotes the development of atherosclerosis, causing disruptions in the body’s hormone levels and changes in the structural function of organs. Objective The purpose of this study was to investigate the pathological changes in the adrenal gland in a model of atherosclerosis under chronic stress and to verify the expression levels of Sodium-glucose cotransporter (SGLT) 1 and SGLT2 in the adrenal gland and their significance in the changes of adrenal gland. Methods The model mice were constructed by chronic unpredictable stress, high-fat diet, and Apoe-/- knockout, and they were tested behaviorally at 0, 4, 8 and 12 weeks. The state of the abdominal artery was examined by ultrasound, and the pathological changes of the aorta and adrenal glands were observed by histological methods, and the expression levels and distribution of SGLT1 and SGLT2 in the adrenal gland were observed and analyzed by immunofluorescence and immunohistochemistry. The predictive value of SGLT1 and SGLT2 expression levels on intima-media thickness, internal diameter and adrenal abnormalities were verified by receiver operating characteristic (ROC) curves, support vector machine (SVM) and back-propagation (BP) neural network. Results The results showed that chronic stress mice had elevated expression levels of SGLT1 and SGLT2. The model mice developed thickening intima-media and smaller internal diameter in the aorta, and edema, reticular fiber rupture, increased adrenal glycogen content in the adrenal glands. More importantly, analysis of ROC, SVM and BP showed that SGLT1 and SGLT2 expression levels in the adrenal glands could predict the above changes in the aorta and were also sensitive and specific predictors of adrenal abnormalities. Conclusion SGLT1 and SGLT2 could be potential biomarkers of adrenal injury in atherosclerosis under chronic stress.

Berberine (BBR) has a long history of use in the treatment of Rheumatoid arthritis (RA) and is considered one of the most promising natural product for the treatment of RA. However, oral administration of berberine has low bioavailability and requires frequent administration, resulting in poor patient compliance. In this study, we developed a BBR-loaded phospholipid-based phase separation gel (BBR-PPSG) to achieve sustained drug release and long-term therapeutic effect. The stability of BBR-PPSG was verified and it was found that it can be stored for a long time. The pharmacokinetic study on rats and rabbits showed that BBR-PPSG not only achieved 1-month of sustained release, but also significantly increased the area under the curve (AUC) by nearly 9-fold and prolonged the half-life (t1/2) by 10-fold. By constructing rat and rabbit models of RA, we also proved that BBR-PPSG administration once a month effectively alleviated joint swelling, and significantly reduce TNF-α levels in AIA rats and OIA rabbits. Histopathological analysis of rabbit joint sections revealed that after intra-articular injection of BBR-PPSG, the synovial cell layer remained intact, while in the model group, the synovial cells were significantly reduced and exhibited necrosis. MicroCT data analysis showed that the values of Tb.N and Tb. Sp in the BBR-PPSG group were significantly better than those in the model group (p < 0.05). This study addressed the limitations of frequent administration of BBR by developing a phospholipid-based phase separation gel system for berberine delivery, achieving long-term sustained release. The BBR-PPSG demonstrated good biocompatibility, simple preparation and excellent stability, thus holding potential as a novel pharmaceutical formulation for RA treatment.

Introduction Hip fracture is associated with substantial morbidity and mortality, especially among the elderly. Current evidence on the association between cigarette smoking and mortality in hip-fracture patients is controversial. We performed a systematic review and meta-analysis of studies on this association. Methods The databases Medline/PubMed, Embase, Web of Science, and Cochrane Library were searched for studies that estimated the effect of smoking on the risk of mortality in hip-fracture patients. Pooled analyses were conducted of the associations, expressed in relative risk (RR) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I 2 statistic. Study quality was assessed by the modified Newcastle-Ottawa Scale (NOS) and publication bias was evaluated by a funnel plot, Begg’s and Egger’s tests. Subgroup analyses were performed by study design, race/ethnicity, age ≥60 years, smoking status, and follow-up period. Results A total of six articles involving 3739 hip-fracture patients were included in the meta-analysis. Our results indicate that ever-active smoking was significantly associated with an increased risk of death in hip-fracture patients (pooled RR=1.26; 95% CI: 1.08–1.46). In further subgroup analysis, the risk of death was significantly higher in ever-active smokers than in never smokers in White participants (pooled RR=1.23; 95% CI: 1.05–1.44) and elderly aged ≥60 years (pooled RR=1.19; 95% CI: 1.01–1.40), with no significant association in Asian participants (pooled RR=1.42; 95% CI: 0.95–2.11). Current smokers had more risk of death than never smokers (pooled RR=1.26; 95% CI: 1.08–1.46). The association was significant in follow-up periods of ≤1 year (pooled hazard ratio, HR=1.34; 95% CI: 1.05–1.71), 3 years (pooled HR=1.22; 95% CI: 1.05–1.43), and 5 years (pooled HR=1.26; 95% CI: 1.08–1.46). Conclusions Cigarette smoking is associated with an increased risk of mortality in hip-fracture patients, especially in elderly patients aged ≥60 years, current smokers, and White participants. With the extension of follow-up period, the effect on mortality of smoking is profound and lasting.

Abstract Background Early and accurate assessment of lumbar intervertebral disc degeneration (IVDD) is very important to therapeutic strategy. This study aims to correlate and compare the performances of T1ρ, T2 and T2* mapping for Pfirrmann grades and morphologic changes in the IVDD. Methods This prospective study included 39 subjects with 195 lumbar discs. T1ρ, T2 and T2* mapping were performed, and T1ρ, T2 and T2* values of nucleus pulposus (NP), and anterior and posterior annulus fibrosus were measured. IVDD was assessed with Pfirrmann grading and morphologic changes (normal, bulging, herniation and annular fissure). The performances of T1ρ, T2 and T2* relaxation times were compared for detecting early (Pfirrmann grade II-III) and advanced degeneration (Pfirrmann grade IV–V), as well as for morphologic changes. Results T2 relaxation times was strongly corelated with T1ρ and T2* relaxation times. Areas under the curves (AUCs) of T1ρ, T2 and T2* relaxation times of NP were 0.70, 0.87 and 0.80 for early degeneration, and 0.91, 0.95 and 0.82 for advanced degeneration, respectively. AUCs of T1ρ, T2 and T2* relaxation times of NP were 0.78, 0.83 and 0.64 for bulging discs, 0.87, 0.89 and 0.69 for herniated discs, and 0.79, 0.82 and 0.69 for annular tearing, respectively. The AUC of T2 relaxation time was significantly higher than those of T1ρ relaxation times (both P 0.05) but significantly higher than that of T2*relaxation time (P

Based on preparation of co-fermented defatted rice bran (DFRB) using Bacillus subtilis, Saccharomyces cerevisiae, Lactobacillus plantarum and phytase, the present study aimed to evaluate the effects of co-fermented DFRB on growth performance, antioxidant capacity, immune status, gut microbiota and permeability in finishing pigs. Ninety finishing pigs (85.30 ± 0.97 kg) were randomly assigned to 3 treatments (3 replicates/treatment) with a basal diet (Ctrl), a basal diet supplemented with 10% unfermented DFRB (UFR), and a basal diet supplemented with 10% fermented DFRB (FR) for 30 d. Results revealed that the diet supplemented with FR notably (P

Macrophage is located in different tissue to serve diverse functions. Here the authors use mass spectrometry and bulk RNA-sequencing to profile 11 mouse macrophage populations from 8 tissues, and combine their de novo data with public datasets to report an integrated proteomic and transcriptomic landscape of mouse macrophage as a valuable resource.

Objective Excessive salt intake is currently the foremost universal risk factor for controllable chronic disease. This study evaluated the short-term effects of a modest salt intake reduction combined with the Chinese Modified Dietary Approaches to Stop Hypertension (CM-DASH) diet on sodium and potassium intake, mean arterial pressure (MAP), and pulse pressure (PP) in hypertensive patients with type II diabetes. Methods Sixty-one participants were randomized to the intervention group (52% low-sodium salt and DASH) and control group (normal salt and DASH). An 8-week dietary intervention was applied. Daily salt intake, blood pressure (BP), and drug use were recorded every week. Twenty-four-hour urine, casual urine, and blood samples were measured at baseline, the 4th week, and the end of the intervention. Results Fifty-nine patients (25 men) completed the entire study. Sodium intake decreased by 1259.66 (792.76, 1726.56)/705.80 (149.21, 1262.39) mg/day after 4 weeks (intervention: P

Introduction Although some research papers have suggested that smoking may increase mortality in patients with sepsis, no evidence has been produced in this regard. This systematic research evaluated the risk of death in patients with sepsis who were smokers to facilitate better clinical decision making. Material and Methods This is a systematic review registered in PROPERO (CRD42022296654). Searches were conducted to identify suitable studies from the databases of PubMed, Embase, Web of Science and the Cochrane Controlled Register of Trials from January 1980 to June 2021. Two independent reviewers screened the articles using keywords and extracted the data. The Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of evidence. The primary endpoints included the mortality of patients with sepsis. Results Five studies involving 2694 participants were included in our study. Among the five included articles, three studies had an NOS score of 6, while the other two had an NOS score of 7. The results showed that a significantly higher risk of death was observed in smokers with sepsis compared with non-smokers with sepsis (hazard ratio, HR=1.62; 95% CI: 1.11–2.37, p=0.01). Among the patients followed for more than 2 months, the mortality rate of smokers was significantly higher (2.33 times) than that of non-smokers (HR=2.33; 95% CI: 1.83–2.96, p

Acute liver injury (ALI) has an elevated fatality rate due to untimely and ineffective treatment. Although, schisandrin B (SchB) has been extensively used to treat diverse liver diseases, its therapeutic efficacy on ALI was limited due to its high hydrophobicity. Palmitic acid-modified serum albumin (PSA) is not only an effective carrier for hydrophobic drugs, but also has a superb targeting effect via scavenger receptor-A (SR-A) on the M1 macrophages, which are potential therapeutic targets for ALI. Compared with the common macrophage-targeted delivery systems, PSA enables site-specific drug delivery to reduce off-target toxicity. Herein, we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI. In vitro, compared with human serum albumin encapsulated SchB nanoparticles (SchB-HSA NPs), the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide (LPS) stimulated Raw264.7 (LAR) cells, and LAR cells took up PSA NPs 8.79 times more than HSA NPs. As expected, the PSA NPs also accumulated more in the liver. Moreover, SchB-PSA NPs dramatically reduced the activation of NF-κB signaling, and significantly relieved inflammatory response and hepatic necrosis. Notably, the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%. Hence, SchB-PSA NPs are promising to treat ALI.

IntroductionThis study investigates the process data from scientific inquiry tasks of fair tests [requiring test-takers to manipulate a target variable while keeping other(s) constant] and exhaustive tests (requiring test-takers to construct all combinations of given variables) in the National Assessment of Educational Progress program.MethodsWe identify significant associations between item scores and temporal features of preparation time, execution time, and mean execution time.ResultsReflecting, respectively, durations of action planning and execution, and execution efficiency, these process features quantitatively differentiate the high- and low-performing students: in the fair tests, high-performing students tended to exhibit shorter execution time than low-performing ones, but in the exhaustive tests, they showed longer execution time; and in both types of tests, high-performing students had shorter mean execution time than low-performing ones.DiscussionThis study enriches process features reflecting scientific problem-solving process and competence and sheds important light on how to improve performance in large-scale, online delivered scientific inquiry tasks.

The combined use of Through Silicon Via (TSV) and metal lines, referred to as TSV-metal lines, is an essential structure in three-dimensional integrated circuits. In-depth research into the electromigration failure mechanism of TSV and the microstructure evolution can serve as theoretical guidance for optimizing three-dimensional stacking. This article conducted electromigration experiments on TSV-metal line structural samples at current densities of 1.0 × 105 A/cm2, 5 × 105 A/cm2, and 1 × 106 A/cm2. Additionally, Electron Back Scattered Diffraction (EBSD) technology was employed to systematically investigate the microstructural evolution of the TSV-metal line structure profiles before and after the application of electrical testing. The results indicate that the current induces a change in the crystal orientation at the TSV-metal interface (TSV/metal interface) and the bottom metal line. This phenomenon notably depends on the initial angle between the grain orientation and the current flow direction. When the angle between the current direction and the grain orientations [001] and [010] is relatively large, the crystals are more likely to deviate in the direction where the angle between the grain orientation and the current is smaller. This is because, at this point, the current direction is precisely perpendicular to the crystal plane family, where the atomic density is lowest, and the energy required for electron transport is minimal. Therefore, the current readily rotates in the direction of this crystal orientation. Before the electromigration tests, areas with a high level of misorientation were primarily concentrated at the TSV/metal interface and the corners of the TSV-metal line. However, these areas were found to be more prone to developing voids after the tests. It is conjectured that the high misorientation level leads to elevated stress gradients, which are the primary cause of cracking failures in the TSV-metal line. As the current density increases from 5 × 105 A/cm2 to 1 × 106 A/cm2, the electromigration failure phenomena in the TSV become even more severe.

The cohesive performance and durability of the bonding layer with semiconductor substrates are of paramount importance for realizing the high thermal conductivity capabilities of diamond. Utilizing electron beam evaporation and the room-temperature, low-pressure bonding process, robust adhesion between diamonds and silicon substrates has been achieved through the application of the metal modification layer comprised of Ti/Cu/Ti/Au (5/300/5/50 nm). Characterization with optical microscopy and atomic force microscopy reveals the uniformity and absence of defects on the surface of the deposited layer. Observations through X-ray and scanning acoustic microscopy indicate no discernible bonding defects. Scanning electron microscopy observation and energy-dispersive spectroscopy analysis of the fracture surface show distinct fracture features on the silicon substrate surface, indicating that the bonding strength of the Ti/Cu/Ti/Au metallization layer surpasses that of the base material. Furthermore, the fracture surface exhibits the presence of Cu and trace amounts of Ti, suggesting that the fracture also occurs at the interface between Ti and Cu. Characterization of the metal modification layer using X-ray diffraction reveals significant lattice distortion in the Ti layer, leading to noticeable stress accumulation within the crystalline structure. Thermal–mechanical fatigue simulations of the Ti/Cu/Ti/Au metal modification layer indicate that, owing to the difference in the coefficient of thermal expansion, the stress exerted by the Cu layer on the Ti layer results in the accumulation of fatigue damage within the Ti layer, ultimately leading to a reduction in its strength and eventual failure.

Abstract Introduction Central lymph node status in papillary thyroid microcarcinoma (PTMC) plays an important role in treatment decision-making clinically, however, it is not easy to predict central lymph node metastasis (CLNM). The present work focused on finding the more rational alternative for evaluating central lymph node status while identifying influencing factors to construct a model to predict CLNM incidence. Methods In this study, we retrospectively analyzed the typical sonographic and clinicopathologic features of 546 PTMC patients who underwent surgery, among which, the data of 382 patients were recruited in the training cohort and that of 164 patients in the validation cohort. Based on the outcome of the training cohort, significant influencing factors were further identified through univariate analysis and were considered as independent variables in multivariable logistic regression analysis and incorporated in and presented with a nomogram. Results In total, six independent predictors, including the age, sex, tumor size, multifocality, capsular invasion, Hashimotos thyroiditis were entered into the nomogram. Both internal validation and external validation revealed the favorable discrimination of our as-constructed nomogram. Calibration curves exhibited high consistency. As suggested by decision-curve analyses, the as-constructed nomogram might be applied in clinic. Besides, the model also distinguished patients according to risk stratification. Conclusions The novel nomogram containing remarkable influencing factors for CLNM cases was established in the present work. The nomogram can assist clinicians in clinical decision-making.

Abstract Sentiment word embedding has been extensively studied and used in sentiment analysis tasks. However, most existing models have failed to differentiate high‐frequency and low‐frequency words. Accordingly, the sentiment information of low‐frequency words is insufficiently captured, thus resulting in inaccurate sentiment word embedding and degradation of overall performance of sentiment analysis. A Bayesian estimation‐based sentiment word embedding (BESWE) model, which aims to precisely extract the sentiment information of low‐frequency words, has been proposed. In the model, a Bayesian estimator is constructed based on the co‐occurrence probabilities and sentiment probabilities of words, and a novel loss function is defined for sentiment word embedding learning. The experimental results based on the sentiment lexicons and Movie Review dataset show that BESWE outperforms many state‐of‐the‐art methods, for example, C&W, CBOW, GloVe, SE‐HyRank and DLJT1, in sentiment analysis tasks, which demonstrate that Bayesian estimation can effectively capture the sentiment information of low‐frequency words and integrate the sentiment information into the word embedding through the loss function. In addition, replacing the embedding of low‐frequency words in the state‐of‐the‐art methods with BESWE can significantly improve the performance of those methods in sentiment analysis tasks.

As endogenous courier vesicles, exosomes play crucial roles in macromolecule transmission and intercellular communication. Therefore, exosomes have drawn increasing attention as biomimetic drug-delivery vehicles over the past few years. However, few studies have investigated the encapsulation of peptide/protein drugs into exosomes for oral administration. Additionally, the mechanisms underlying their biomimetic properties as oral delivery vehicles remain unknown. Herein, insulin-loaded milk-derived exosomes (EXO@INS) were fabricated and the in vivo hypoglycemic effect was investigated on type I diabetic rats. Surprisingly, EXO@INS (50 and 30 IU/kg) elicited a more superior and more sustained hypoglycemic effect compared with that obtained with subcutaneously injected insulin. Further mechanism studies indicated that the origin of excellent oral-performance of milk-derived exosomes combined active multi-targeting uptake, pH adaptation during gastrointestinal transit, nutrient assimilation related ERK1/2 and p38 MAPK signal pathway activation and intestinal mucus penetration. This study provides the first demonstration that multifunctional milk-derived exosomes offer solutions to many of the challenges arising from oral drug delivery and thus provide new insights into developing naturally-equipped nanovehicles for oral drug administration.