Search Results (1,048)

Inflammatory arthritis (IA) is a chronic condition marked by joint dysfunction and pain, posing significant challenges for effective drug delivery. This study separated Perilla frutescens leaf-derived exosome-like nanovesicles (PFE) to effectively penetrate the stratum corneum barrier. These nanovesicles and indomethacin (IND) were subsequently developed into a nanogel designed for topical drug delivery systems (PFE-IND-GEL). PFE exhibited a typical vesicular structure with a mean diameter of 98.4 ± 1.3 nm. The hydrodynamic size and zeta potential of PFE-IND-GEL were 129.6 ± 5.9 nm and −17.4 ± 1.9 mV, respectively. Mechanistic investigations in HaCaT keratinocytes showed that PFE significantly downregulated tight junction proteins (ZO-1 and Occludin, p < 0.01) via modulation of the IL-17 signaling pathway, as evidenced by transcriptomic analysis. In a sodium urea crystal-induced rat IA model, the topical application of PFE-IND-GEL significantly reduced joint swelling (p < 0.05) and serum levels of inflammatory cytokines (IL-6, IL-1α, TNF-α) compared to control groups. Histopathological analysis confirmed the marked attenuation of synovial inflammation and cartilage preservation in treated animals. These findings underscore the dual role of PFE as both a topical permeation enhancer and an anti-inflammatory agent, presenting a promising strategy for managing IA. Full article

To enable safe and effective human–robot collaboration (HRC) in smart manufacturing, it is critical to seamlessly integrate sensing, cognition, and prediction into the robot controller for real-time awareness, response, and communication inside a heterogeneous environment (robots, humans, and equipment). The proposed approach takes advantage of the prediction capabilities of nonlinear model predictive control (NMPC) to execute safe path planning based on feedback from a vision system. To satisfy the requirements of real-time path planning, an embedded solver based on a penalty method is applied. However, due to tight sampling times, NMPC solutions are approximate; therefore, the safety of the system cannot be guaranteed. To address this, we formulate a novel safety-critical paradigm that uses an exponential control barrier function (ECBF) as a safety filter. Several common human–robot assembly subtasks have been integrated into a real-life HRC assembly task to validate the performance of the proposed controller and to investigate whether integrating human pose prediction can help with safe and efficient collaboration. The robot uses OptiTrack cameras for perception and dynamically generates collision-free trajectories to the predicted target interactive position. Results for a number of different configurations confirm the efficiency of the proposed motion planning and execution framework, with a 23.2% reduction in execution time achieved for the HRC task compared to an implementation without human motion prediction. Full article

Against the backdrop of China’s fast-growing digital economy and its financial inclusion agenda, there is still little city-level evidence on whether the e-CNY pilot accelerates financial deepening at the grassroots. Using a balanced panel of 271 prefecture-and-above cities for 2016–2022, this study employs a staggered difference-in-differences (SDID) design augmented by the synthetic control method (SCM) to rigorously identify the policy effect of the e-CNY pilot. The results show that the pilot program significantly improves urban financial inclusion, contributing to more equitable access to financial services and supporting inclusive socio-economic development. Mechanism analysis suggests that the effect operates mainly through two channels, a merchant-coverage channel and a transaction-scale channel, with the former contributing the majority of the overall effect. Incorporating a migration-based mobility index shows that most studies’ focus on the merchant-coverage effect is amplified in cities under tight mobility restrictions but wanes where commercial networks are already saturated, whereas the transaction-scale channel is largely insensitive to mobility shocks. Heterogeneity tests further indicate stronger gains in non-provincial capital cities and in the eastern and central regions. Overall, the study uncovers a “penetration-inclusion” network logic and provides policy insights for advancing sustainable financial inclusion through optimized terminal deployment, merchant incentives, and diversified scenario design. Full article

In order to study the problem of obvious wall thinning in the wellbore caused by proppant backflow and sand production under throttling conditions in tight gas wells. Based on the gas-phase control equation, particle motion equation, and erosion model, the wellbore erosion model is established. The distribution law of pressure, temperature, and velocity trace fields under throttling conditions is analyzed, and the influences of different throttling pressures, particle diameters, and particle mass flows on wellbore erosion are analyzed. The flow field at the nozzle changes drastically, and there is an obvious pressure drop, temperature drop, and velocity rise. When the surrounding gas is completely mixed, the physical quantity gradually stabilizes. The erosion shape of the wellbore outlet wall has a point-like distribution. The closer to the throttle valve outlet, the more intense the erosion point distribution is. Increasing the inlet pressure and particle mass flow rate will increase the maximum erosion rate, and increasing the particle diameter will reduce the maximum erosion rate. The particle mass flow rate has the greatest impact on the maximum erosion rate, followed by the particle diameter. The erosion trend was predicted using multiple regression model fitting of the linear interaction term. The research results can provide a reference for the application of downhole throttling technology and wellbore integrity in tight gas exploitation. Full article

Suckling is crucial for piglet intestinal development and gut health, as it improves resilience during the challenging weaning phase and promotes subsequent growth. IPS, comprising Na⁺/K⁺ ions, whey protein, and glucose, has been shown to have positive effects on animal growth and intestinal health. The objectives of this study were to assess the impact of IPS consumption on the growth performance, immunity, intestinal growth and development, and microbiota structure of suckling piglets. A total of 160 newborn piglets were randomly divided into control and IPS groups, with IPS supplementation starting from 2 to 8 days after birth and continuing until 3 days before weaning. The findings revealed that IPS boosted the body weight at 24 days by 3.6% (p < 0.05) and improved the body weight gain from 16 to 24 days by 15.7% (p < 0.05). Additionally, the jejunal villus height and villus height to crypt depth ratio in the IPS group were notably increased to 1.08 and 1.31 times (p < 0.05), respectively, compared to the control group. Furthermore, IPS elevated the plasma levels of IgA and IgM, reduced the plasma levels of blood urea nitrogen (BUN), and enhanced the content of secretory immunoglobulin A (SIgA) in the jejunal mucosa of suckling piglets. Furthermore, IPS upregulated the mRNA expression of tight junction proteins GLP-2, ZO-1, and Claudin-1 in jejunal tissue, while downregulating the regulatory genes in the Toll-like pathway, including MyD88 and TLR-4 (p < 0.05). The analysis of gut microbiota indicated that IPS altered the relative abundance of gut microbes, with an increase in beneficial bacteria like Alloprevotella and Bacteroides. In conclusion, this study demonstrates that IPS supplementation enhances weaning weight, growth performance, immune function, and intestinal development in piglets, supporting the integration of IPS supplementation in the management of pre-weaning piglets. Full article

Weaning stress damages the intestines and disrupts the intestinal barrier in piglets, which significantly impacts the pig farming industry’s economy. We aimed to examine the effects of ShenQiGan extract (CAG) on intestinal barrier function and explore the underlying molecular mechanisms in stress-challenged weaned piglets. The experimental design involved 80 weaned piglets aged 28 days (with an average body weight of 7.78 ± 0.074 kg) that were randomly allocated into four groups: Control, LCAG (0.1% CAG), MCAG (0.5% CAG), and HCAG (1.0% CAG). After a 28-day trial period, the growth performance and incidence of diarrhea in piglets were evaluated. CAG increased the average daily gain of weaned piglets, reduced the feed-to-gain ratio, and decreased the incidence of diarrhea. It significantly lowered serum inflammatory cytokine levels while elevating immunoglobulin levels. The supplement notably enhanced concentrations of acetic acid, propionic acid, butyric acid, and isobutyric acid. Furthermore, CAG demonstrated intestinal morphology restoration and upregulation of tight junction proteins and MUC2 protein expression in jejunum. At the mRNA level, it significantly upregulated the expression of Occludin, Claudin1, and MUC2 genes. CAG improves growth performance and mitigates diarrhea in weaned piglets by enhancing intestinal barrier integrity, modulating systemic inflammatory responses, elevating immunoglobulin levels, and promoting short-chain fatty acids (SCFAs) production in the cecum. Full article

The design and optimization of drive distribution strategies are critical for enhancing the performance of Formula Student electric racing cars, which face demanding operational conditions such as rapid acceleration, tight cornering, and variable track surfaces. Given the increasing complexity of racing environments and the need for adaptive control solutions, a multi-mode adaptive drive distribution strategy for four-wheel-drive Formula Student electric racing cars is proposed in this study to meet specialized operational demands. Based on the dynamic characteristics of standardized test scenarios (e.g., straight-line acceleration and figure-eight loop), two control modes are designed: slip-ratio-based anti-slip control for longitudinal dynamics and direct yaw moment control for lateral stability. A CarSim–Simulink co-simulation platform is established, with test scenarios conforming to competition standards, including variable road adhesion coefficients (μ is 0.3–0.9) and composite curves. Simulation results indicate that, compared to conventional PID control, the proposed strategy reduces the peak slip ratio to the optimal range of 18% during acceleration and enhances lateral stability in the figure-eight loop, maintaining the sideslip angle around −0.3°. These findings demonstrate the potential for significant improvements in both performance and safety, offering a scalable framework for future developments in racing vehicle control systems. Full article

Porcine epidemic diarrhea virus (PEDV) infection induces severe, often fatal, watery diarrhea and vomiting in neonatal piglets, characterized by profound dehydration, villus atrophy, and catastrophic mortality rates approaching 100% in unprotected herds. This study developed a composite probiotic from Min-pig-derived Lactobacillus crispatus LCM233, Ligilactobacillus salivarius LSM231, and Lactiplantibacillus plantarum LPM239, which exhibited synergistic growth, potent acid/bile salt tolerance, and broad-spectrum antimicrobial activity against pathogens. In vitro, the probiotic combination disrupted pathogen ultrastructure and inhibited PEDV replication in IPI-2I cells. In vivo, PEDV-infected piglets administered with the multi-strain probiotic exhibited decreased viral loads in anal and nasal swabs, as well as in intestinal tissues. This intervention was associated with the alleviation of diarrhea symptoms and improved weight gain. Furthermore, the multi-strain probiotic facilitated the repair of intestinal villi and tight junctions, increased the number of goblet cells, downregulated pro-inflammatory cytokines, enhanced the expression of barrier proteins, and upregulated antiviral interferon-stimulated genes. These findings demonstrate that the multi-strain probiotic mitigates PEDV-induced damage by restoring intestinal barrier homeostasis and modulating immune responses, providing a novel strategy for controlling PEDV infections. Full article

The development of functional endothelial monolayers on synthetic vascular grafts remains challenging, particularly for small-diameter vessels (<6 mm) prone to thrombosis. Here, we present a pharmacological strategy combining 8-(4-chlorophenylthio) adenosine 3′,5′-cyclic monophosphate sodium salt (pCPT-cAMP, a tight junction promoter) with nitric oxide/cGMP pathway agonists 3-morpholinosydnonimine (SIN-1), captopril, and sildenafil) to enhance endothelialization. In human umbilical vein endothelial cells (HUVECs), this four-agent cocktail induced a flat, extended phenotype with a 3-fold increased cell area and 57.5% fewer cells required for surface coverage compared to controls. Immunofluorescence analysis revealed enhanced ZO-1 expression and continuous tight junction formation, while sustained nitric oxide (NO) production (3.9-fold increase) and restored prostacyclin (PGI₂) secretion demonstrated preserved endothelial functionality. Anticoagulation assays confirmed a significant reduction in thrombus formation (p < 0.01) via dual inhibition of platelet activation and thrombin binding. These findings establish a synergistic drug combination that promotes rapid endothelialization while maintaining antithrombogenic activity, offering a promising solution for small-diameter vascular grafts. Further studies should validate long-term stability and translational potential in preclinical models. Full article

Capturing CO₂ emitted by coal chemical enterprises and injecting it into oil reservoirs not only effectively improves the recovery rate and development efficiency of tight oil reservoirs in the Ordos Basin but also addresses the carbon emission problem constraining the development of the region. Since initiating field experiments in 2012, the Ordos Basin has become a significant base for CCUS (Carbon capture, Utilization, and Storage) technology application and demonstration in China. However, over the years, projects have primarily focused on enhancing the recovery rate of CO₂ flooding, while issues such as potential reservoir damage and its extent have received insufficient attention. This oversight hinder the long-term development and promotion of CO₂ flooding technology in the region. Experimental results were comprehensively analyzed using techniques including nuclear magnetic resonance (NMR), X-ray diffraction (XRD), scanning electron microscopy (SEM), inductively coupled plasma (ICP), and ion chromography (IG). The findings indicate that under current reservoir temperature and pressure conditions, significant asphaltene deposition and calcium carbonate precipitation do not occur during CO₂ flooding. The reservoir’s characteristics-high feldspar content, low carbon mineral content, and low clay mineral content determine that the primary mechanism affecting physical properties under CO₂ flooding in the Chang 4 + 5 tight sandstone reservoir is not, as traditional understand, carbon mineral dissolution or primary clay mineral expansion and migration. Instead, feldspar corrosion and secondary particles migration are the fundamental reasons for the changes in reservoir properties. As permeability increases, micro pore blockage decreases, and the damaging effect of CO₂ flooding on reservoir permeability diminishes. Permeability and micro pore structure are therefore significant factors determining the damage degree of CO₂ flooding inflicts on tight reservoirs. In addition, temperature and pressure have a significant impact on the extent of reservoir damage caused by CO₂ flooding in the study region. At a given reservoir temperature, increasing CO₂ injection pressure can mitigate reservoir damage. It is recommended to avoid conducting CO₂ flooding projects in reservoirs with severe pressure attenuation, low permeability, and narrow pore throats as much as possible to prevent serious damage to the reservoir. At the same time, the production pressure difference should be reasonably controlled during the production process to reduce the risk and degree of calcium carbonate precipitation near oil production wells. Full article

Glioblastoma is the most common and aggressive malignant primary brain tumour. Patients with glioblastoma have a median survival of only around 14.6 months after diagnosis, despite the availability of various conventional multimodal treatments including chemotherapy, radiation therapy, and surgery. Therefore, photodynamic therapy (PDT) has emerged as an advanced, selective and more controlled therapeutic approach, which has minimal systemic toxicity and fewer side effects. PDT is a less invasive therapy that targets all cells or tissues that possess the photosensitizer (PS) itself, without affecting the surrounding healthy tissues. Polymeric NPs (PNPs) as carriers can improve the targeting ability and stability of PSs and co-deliver various anticancer agents to achieve combined cancer therapy. Because of their versatile tuneable features, these PNPs have the capacity to open tight junctions of the blood–brain barrier (BBB), easily transport drugs across the BBB, protect against enzymatic degradation, prolong the systemic circulation, and sustainably release the drug. Conjugated polymer NPs, poly(lactic-co-glycolic acid)-based NPs, lipid–polymer hybrid NPs, and polyethylene-glycolated PNPs have demonstrated great potential in PDT owing to their unique biocompatibility and optical properties. Although the combination of PDT and PNPs has great potential and can provide several benefits over conventional cancer therapies, there are several limitations that are hindering its translation into clinical use. This review aims to summarize the recent advances in the combined use of PNPs and PDT in the case of glioblastoma treatment. By evaluating various types of PDT and PNPs, this review emphasizes how these innovative approaches can play an important role in overcoming glioblastoma-associated critical challenges, including BBB and tumour heterogeneity. Furthermore, this review also discusses the challenges and future directions for PNPs and PDT, which provides insight into the potential solutions to various problems that are hindering their clinical translation in glioblastoma treatment. Full article

In tight sandstone gas reservoirs, proppant flowback severely limits stable gas production. This study uses laboratory flowback experiments and field analyses of the ShaXimiao tight sandstone in the Wenxing gas area to investigate the mechanisms controlling sand production. The experiments show that displacing fluid viscosity significantly affects the critical sand-flow velocity: with high-viscous slickwater (5 mPa·s), the critical velocity is 66% lower than with low-viscous formation water (1.15 mPa·s). The critical velocity for coated proppant is three times that of the mixed quartz sand and coated proppant. If the confining pressure is maintained, but the flow rate is further increased after the proppant flowback, a second instance of sand production can be observed. X-ray diffraction (XRD) tests were conducted for sand produced from practical wells to help find the sand production reasons. Based on experimental and field data analysis, sand production in Well X-1 primarily results from proppant detachment during rapid shut-in/open cycling operations, while in Well X-2, it originates from proppant crushing. The risk of formation sand production is low for both wells (the volumetric fraction of calcite tested from the produced sands is smaller than 0.5%). These findings highlight the importance of fluid viscosity, proppant consolidation, and pressure management in controlling sand production. Full article

The Carboniferous–Permian tight sandstone gas reservoirs in the Shenfu area of the Ordos Basin in China are characterized by the widespread development of multiple formations. However, significant differences exist among the tight sandstones of different formations, and their formation mechanisms and key controlling factors remain unclear, hindering the effective selection and development of favorable tight gas intervals in the study area. Through comprehensive analysis of casting thin section (CTS), scanning electron microscopy (SEM), cathodoluminescence (CL), X-ray diffraction (XRD), particle size and sorting, porosity and permeability data from Upper Paleozoic tight sandstone samples, combined with insights into depositional environments, burial history, and chemical reaction processes, this study clarifies the characteristics of tight sandstone reservoirs, reveals the key controlling factors of reservoir quality, confirms the differential evolutionary mechanisms of tight sandstone of different formations, reconstructs the diagenetic sequence, and constructs an evolution model of reservoir minerals and porosity. The research results indicate depositional processes laid the foundation for the original reservoir properties. Sandstones deposited in tidal flat and deltaic environments exhibit superior initial reservoir qualities. Compaction is a critical factor leading to the decline in reservoir quality across all formations. However, rigid particles such as quartz can partially mitigate the pore reduction caused by compaction. Early diagenetic carbonate cementation reduces reservoir quality by occupying primary pores and hindering the generation of secondary porosity induced by acidic fluids, while later-formed carbonate further densifies the sandstone by filling secondary intragranular pores. Clay mineral cements diminish reservoir porosity and permeability by filling intergranular and intragranular pores. The Shanxi and Taiyuan Formations display relatively poorer reservoir quality due to intense illitization. Overall, the reservoir quality of Benxi Formation is the best, followed by Xiashihezi Formation, with the Taiyuan and Shanxi Formations exhibiting comparatively lower qualities. Full article

Background/Objectives: Colitis is a chronic condition affecting millions worldwide. Purple muscadine wine polyphenols have a unique composition and possible disease-preventive properties. This study aims to determine how dealcoholized muscadine wine (DMW) affects the development of colitis and gut microbiome in IL-10^−/− mice, compared to wild types (WT). Methods: Six-week-old male IL-10^−/− and WT C57BL/6 mice were fed either a DMW-supplemented diet (4.8% v/w) or a control diet based on AIN-93M for 154 days. Colitis severity was evaluated by disease activity, intestinal permeability, gene expression of cytokines and tight junction proteins in the colon, and inflammatory cytokines in the serum. Fecal samples were collected for gut microbiome profiling via 16S rRNA gene sequencing. Results: DMW contained predominantly anthocyanins and a significant amount of ellagic acid. IL-10^−/− mice developed mild colitis as indicated by the disease activity index. DMW × gene interactions decreased intestinal permeability, colonic mRNA levels of IL-1β, and serum TNF-α in the IL-10^−/− mice. DMW suppressed the colonic mRNA levels of IL-6, enhanced the gene expression of ZO-1, but did not influence the mRNA level of TNF-α or occludin. While DMW did not alter α-diversity of the gut microbiome, it significantly influenced β-diversity in the WT mice. DMW significantly reduced the relative abundances of Akkermansia in the IL-10^−/− and WT mice. DMW and DMW×gene interaction decreased the relative abundance of Parasutterella only in IL-10^−/− mice. Conclusions: These results suggested that polyphenols from DMW interacted with genes to moderately alleviate the development of colitis in IL-10^−/− mice and could be a useful dietary strategy for IBD prevention. Full article

Background/Objectives: This study investigated the effects of chestnut tannic acid (TA) on the growth performance, the expression of tight junction proteins and the composition of the gut microbiota of weaned piglets, which could provide novel insights into the application of TA in swine production. Methods: In a 42-day trial, 180 healthy, 21-day-old Duroc × Landrace × Yorkshire piglets were randomly assigned to a Control group and four treatment groups (TA1–4), fed commercial diets supplemented with 0, 0.06%, 0.12%, 0.18% or 0.24% TA. Each group had six replicates of six pigs each. Results: The average daily gain in all TA groups, the jejunal and ileal villus height and the villus height-to-crypt depth ratio in the TA3 and TA4 groups were markedly increased (p < 0.05). The mRNA levels of MUC2 and ZO-1 were upregulated in the TA3 group, as were those of MUC4 in the jejunum and ileum and claudin in the duodenum and ileum; glutathione peroxidase and total antioxidant capacity were upregulated in the duodenum and jejunum in the TA3 group, and total superoxide dismutase was increased in all the TA2 groups (p < 0.05). Conversely, the malondialdehyde significantly decreased in all the TA groups (p < 0.05). TA supplementation improved the alpha diversity of the intestinal microflora and augmented probiotic abundance while reducing that of pathogenic bacteria. The contents of acetic, isobutyric, valeric, isovaleric, hexanoic and propionic acids, as well as total short-chain fatty acids (SCFA), were higher in the TA2 and TA3 groups (p < 0.05). Conclusions: TA inclusion in piglet diets improved the intestinal environment by upregulating the antioxidant enzymes, improving intestinal morphology and promoting probiotic growth and SCFA production while reducing pathogenic bacterial abundance, consequently enhancing the gut barrier and the growth of weaned piglets. Full article