Bovine mastitis harms milk quality and cattle health. Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) are well-known milk-derived bioactive peptides with anti-inflammatory activity. However, the impact of VPP and IPP on mastitis remain unknown. This study aimed to investigate the anti-inflammatory effects and the underlying mechanisms of VPP and IPP in lipopolysaccharide (LPS)-induced inflammation. When cells were treated with LPS (1 µg/mL) for 24 h, the protein levels of pro-inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin(IL)-1β and IL-6)) and chemokine (monocyte chemotactic protein-1 (MCP-1)) were markedly increased, and the protein level of anti-inflammatory cytokine (IL-10) was reduced. Both VPP and IPP with concentrations of 50 and 100 µM reversed these phenomena and further inhibited the protein expression of β-casein induced by LPS. In a mouse mastitis model, different concentrations of VPP and IPP (300, 600 µM/kg) pretreatment alleviated histopathological lesions in the mammary gland and suppressed the mRNA expression of TNFα, IL1β, and IL6 induced by LPS. VPP and IPP also maintained the integrity of the blood–milk barrier in mice. RNA-seq analyses indicated that enriched phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways likely contribute to the changes observed (P < 0.05 and |log2 fold change (FC)| ≥ 1). Notably, fibronectin was identified as an important hub by protein–protein interaction (PPI) analysis and molecular docking combined with molecular dynamics simulation. In summary, VPP and IPP exerted a protective effect on LPS-induced inflammation by regulating PI3K/AKT signaling pathway via fibronectin.

Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive and prevalent breast cancer subtype that lacks targeted therapies. This study aims to investigate whether the niclosamide derivative HJC0152 can modulate tumor-derived PD-L1 expression and enhance the effectiveness of anti-PD-1 immunotherapy in treating TNBC. Methods/Study Population: Niclosamide derivative HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human TNBC cell line (MDA-MB-231) was treated with HJC0152, and activation of the STAT3 signaling pathway was evaluated using Western blotting. RNA-Seq was employed to analyze the expression of protein-coding genes, particularly those related to immune response. To study therapeutic potential in vivo, TNBC mouse models will be treated with single agent treatments as well as a combination therapy of HJC0152 and anti-PD-1. Tumor volume and mass will be measured over time to determine growth inhibition. Results/Anticipated Results: Preliminary studies indicate that HJC0152 exhibits enhanced solubility compared to Niclosamide, along with high anticancer potency both in vitro and in vivo. HJC0152 was found to effectively inhibit the activation of phosphorylated STAT3 (p-STAT3) in MDA-MB-231 cells, a key signaling pathway associated with cancer progression and immune evasion. RNA-Seq analysis of HJC0152-treated MDA-MB-231 cells revealed a decrease in PD-L1 expression, an essential immune checkpoint protein involved in tumor immune suppression. These findings suggest that HJC0152 is a promising immune modulator that may enhance the efficacy of immune checkpoint blockade therapy for TNBC. Discussion/Significance of Impact: This study explores an innovative immunotherapy for TNBC using the Niclosamide derivative HJC0152, which inhibits STAT3 signaling and downregulates PD-L1. Results from this study will provide a foundation for HJC0152’s inclusion in clinical trials and potentially offer a new and promising therapeutic option for TNBC treatment.

Little is known about the association between iodine nutrition status and bone health. The present study aimed to explore the connection between iodine nutrition status, bone metabolism parameters, and bone disease (osteopenia and osteoporosis). A cross-sectional survey was conducted involving 391, 395, and 421 adults from iodine fortification areas (IFA), iodine adequate areas (IAA), and iodine excess areas (IEA) of China. Iodine nutrition status, bone metabolism parameters and BMD were measured. Our results showed that, in IEA, the urine iodine concentrations (UIC) and serum iodine concentrations (SIC) were significantly higher than in IAA. BMD and Ca2+ levels were significantly different under different iodine nutrition levels and the BMD were negatively correlated with UIC and SIC. Univariate linear regression showed that gender, age, BMI, menopausal status, smoking status, alcohol consumption, UIC, SIC, free thyroxine, TSH, and alkaline phosphatase were associated with BMD. The prevalence of osteopenia was significantly increased in IEA, UIC ≥ 300µg/L and SIC > 90µg/L groups. UIC ≥ 300µg/L and SIC > 90µg/L were risk factors for BMD T value < -1.0 SD. In conclusion, excess iodine can not only lead to changes in bone metabolism parameters and BMD, but is also a risk factor for osteopenia and osteoporosis.

This study investigates the effects of fat emulsion-based early parenteral nutrition in patients following hemihepatectomy, addressing a critical gap in clinical knowledge regarding parenteral nutrition after hemihepatectomy. We retrospectively analysed clinical data from 274 patients who received non-fat emulsion-based parenteral nutrition (non-fatty nutrition group) and 297 patients who received fat emulsion-based parenteral nutrition (fatty nutrition group) after hemihepatectomy. Fat emulsion-based early parenteral nutrition significantly reduced levels of post-operative aspartate aminotransferase, total bilirubin and direct bilirubin, while minor decreases in red blood cell and platelet counts were observed in the fatty nutrition group. Importantly, fat emulsion-based early parenteral nutrition shortened lengths of post-operative hospital stay and fasting duration, but did not affect the incidence of short-term post-operative complications. Subgroup analyses revealed that the supplement of n-3 fish oil emulsions was significantly associated with a reduced inflammatory response and risk of post-operative infections. These findings indicate that fat emulsion-based early parenteral nutrition enhances short-term post-operative recovery in patients undergoing hemihepatectomy.

This paper provides an overview of the current status of ultrafast and ultra-intense lasers with peak powers exceeding 100 TW and examines the research activities in high-energy-density physics within China. Currently, 10 high-intensity lasers with powers over 100 TW are operational, and about 10 additional lasers are being constructed at various institutes and universities. These facilities operate either independently or are combined with one another, thereby offering substantial support for both Chinese and international research and development efforts in high-energy-density physics.

Adaptation to the dynamic environment and variable task sequence is the critical ability for robot navigation and task execution. The Cyclic Networking Rapidly-exploring Random Tree (CNRRT) method is proposed to obtain the optimal path in real time and realize long-term path planning ability in a complex dynamic environment. The cyclic branch is introduced to the acyclic graph of Rapidly-exploring Random Tree (RRT) method, which forms a decentralized path network in the configuration space. An iterative searching strategy is built to search for the optimal path in the network. The branch prune, reconnection, and regrowth processes enable the decentralized network to efficiently respond to dynamic changes in the environment. The CNRRT can search for the real-time optimal path in the dynamic environment, dealing with the configuration and task changes robustly. Besides, the CNRRT is consistent for scenarios with long-term task sequence without significant performance fluctuation. Simulations and real-world comparative experiments verify the effectiveness of the proposed method.

Urban air mobility (UAM) utilising novel transportation tools is gradually being recognised as a significant means to alleviate ground transportation pressures, vertiports which serve as pivotal nodes in UAM require efficient methods for assessing its operational capacity to develop an appropriate operational strategy and help to design vertiport ground infrastructure scientifically. This study proposes a multi-dimensional assessment method for the capacity of vertiports considering throughput and quality of service based on genetic algorithm (CEGA). The method comprehensively considers constraints such as unmanned aerial vehicle (UAV) safety separation, battery endurance, number of landing vertipads and UAV speed. The experimental results indicate that the vertiport with the scheduling algorithm proposed by this study has a larger capacity and experiences fewer delay than the vertiport with first-come-first-served (FCFS) algorithm when the vertiport has the same limited number of vertipads. Different proportions of UAVs significantly affect the quality of service and the degree of operation delays. The weights of vertiport throughput and customer satisfaction are the parameters that represent the importance of throughput and customer satisfaction in the objective function of the capacity assessment model. When the weights of throughput and customer satisfaction are set to 0.8 and 0.2 respectively, the performance of this optimisation model is optimal. This study provides a novel solution for capacity assessment and operation scheduling of vertiports, laying the foundation for improving the efficiency of UAM operations.

Multiple osteoarticular tuberculosis (MOT) represents an uncommon yet severe form of tuberculosis, characterized by a lack of systematic analysis and comprehension. Our objective was to delineate MOT’s epidemiological characteristics and establish a scientific foundation for prevention and treatment. We conducted searches across eight databases to identify relevant articles. Pearson’s chi-square test (Fisher’s exact test) and Bonferroni method were employed to assess osteoarticular involvement among patients of varying age and gender (α = 0.05). The study comprised 98 articles, encompassing 151 cases from 22 countries, with China and India collectively contributing 67.55% of cases. MOT predominantly affected individuals aged 0–30 years (58.94%). Pulmonary tuberculosis was evident in 16.55% of cases, with spinal involvement prevalent (57.62%). Significant differences were noted in trunk, spine, thoracic, and lumbar vertebrae involvement, as well as type I lesions across age groups, increasing with age. Moreover, significant differences were observed in upper limb bone involvement and type II lesions across age groups, decreasing with age. Gender differences were not significant. MOT primarily manifests in China and India, predominantly among younger individuals, indicating age-related variations in osteoarticular involvement. Enhanced clinical awareness is crucial for accurate MOT diagnosis, mitigating missed diagnoses and misdiagnoses.

The development of Maritime Autonomous Surface Ship (MASS) is progressing rapidly within the maritime industry. Degree Two of MASS (MASS-DoA2), balancing human oversight and autonomous efficiency, will likely gain regulatory approval and industry acceptance. MASS-DoA2 possesses different control modes to adapt to various scenarios. However, the control-switching mechanisms among operators at shore control centres, autonomous navigation systems and number of seafarers onboard remain ambiguous, which poses a new risk that may significantly influence navigation safety. This study focuses on MASS-DoA2 and carries out a systematic review of autonomous ship guidelines. A questionnaire was designed based on the review findings, and a survey was carried out among captains and researchers in related fields. The review identified 11 control-switching scenarios with suggested takeover agents and the switching process and outlined the priority relationship between various takeover agents. Finally, a control-switching framework for MASS – DoA2 is proposed. It can serve as a theoretical framework for research on MASS's dynamic degree of autonomy and provide a reference for maritime regulatory authorities in establishing MASS – DoA2 control-switching mechanisms.

Let X be a compact Kähler manifold, and let $L \rightarrow X$ be a holomorphic line bundle equipped with a singular metric h such that the curvature $\mathrm {i}\Theta _{L,h}\geqslant 0$ in the sense of currents. The main result of this paper is the vanishing of $H^n(X,\mathcal {O}(\Omega ^p_X\otimes L)\otimes \mathcal {I}(h))$ for $p\geqslant n-\operatorname {nd}(L,h)+1$, which generalizes Bogomolov’s vanishing theorem and Watanabe’s result.

Cable-guiding mechanisms (CGMs) and the stiffness characteristics directly influence the dynamic features of the cable-driven upper limb rehabilitation robot (PCUR), which will affect PCUR’s performance. This paper introduces a novel CGM design. Given the precision and movement stability considerations of the mechanism, an analytical model is developed. Using this model, we analyze the error of the CGM and derive velocity and acceleration mappings from the moving platform to the cables. Continuity of cable trajectory and tension is rigorously demonstrated. Subsequently, a mathematical model for PCUR stiffness is formulated. Utilizing MATLAB/Simscape Multibody, simulation models for the CGM and stiffness characteristics are constructed. The feasibility of the proposed CGM design is validated through simulation and experimentation, while the influence of stiffness characteristics on PCUR motion stability is comprehensively analyzed.

Nonlinear compression experiments based on multiple solid thin plates are conducted in an ultra-high peak power Ti:sapphire laser system. The incident laser pulse, with an energy of 80 mJ and a pulse width of 30.2 fs, is compressed to 10.1 fs by a thin-plate based nonlinear compression. Significant small-scale self-focusing is observed as ring structures appear in the near-field of the output pulse at high energy. Numerical simulations based on the experimental setup provide a good explanation for the observed phenomena, offering quantitative predictions of the spectrum, pulse width, dispersion and near- and far-field distributions of the compressed laser pulse.