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.

Upper extremity rehabilitation robots have become crucial in stroke rehabilitation due to their high durability, repeatability, and task-specific capabilities. A significant challenge in assessing the comfort performance of these robots is accurately calculating the human-robot interaction forces. In this study, a four-degree-of-freedom (4-DOF) upper extremity rehabilitation robot mechanism, kinematically compatible with the human upper limb, is proposed. Based on this mechanism, an algorithm for estimating human-robot interaction forces is developed using Newton-Euler dynamics. A prototype of the proposed robot is constructed, and a series of comparative experiments are carried out to validate the feasibility of the proposed force estimation approach. The results indicate that the proposed method reliably predicts interaction forces with minimal deviation from experimental data, demonstrating its potential for application in upper limb rehabilitation robots. This work provides a foundation for future studies focused on comfort evaluation and optimization of rehabilitation robots, with significant practical implications for improving patient rehabilitation outcomes.

This article is concerned with the spreading speed and traveling waves of a lattice prey–predator system with non-local diffusion in a periodic habitat. With the help of an associated scalar lattice equation, we derive the invasion speed for the predator. More specifically, when the dispersal kernel of the predator is exponentially bounded, the invasion speed is finite and can be characterized in terms of principal eigenvalues; while the dispersal kernel is algebraically decaying, the invasion speed is infinite and the accelerated spreading rate is obtained. Furthermore, the existence and non-existence of traveling waves connecting the semi-equilibrium point to a uniformly persistent state are established.

This study focused on the effect of the cognitive behavioural therapy (CBT) combined with aripiprazole on cognitive functions and psychological state of schizophrenia patients. Seventy-eight schizophrenia patients were divided into two groups. One group received aripiprazole with conventional nursing treatment for 3 months (control group, n = 39), and the other received aripiprazole with CBT for 3 months (observation group, n = 39) (1 session per week, each session lasting 60 min. In the two groups before and after treatment, the severity of symptoms was evaluated using the Psychiatric Symptom Rating Scale (BPRS). Cognitive function was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Positive and Negative Symptom Scale (PANSS) was utilised to evaluate mental status, while the Generalised Self-Efficacy Scale (GSES) measured psychological state. Additionally, the quality of life was assessed using the General Quality of Life Inventory-74 (GQOLI-74). In the final analysis, post-treatment efficacy and complications for the two groups were counted. Both groups showed significant improvements: BPRS and PANSS scores decreased, while RBANS, GSES, and GQOLI-74 scores increased. The observation group showed greater improvements than the control group. The total improvement rate was 89.74% (35/39) in the observation group, higher than the 71.79% (28/39) in the control group. The complication rate was 33.33% (13/39) in the observation group and 38.46% (15/39) in the control group. The treatment of CBT combined with aripiprazole for schizophrenia has a significantly positive effect on the cognitive functions and psychological state of patients.

Rhopalosiphum padi is an important grain pest, causing severe losses during crop production. As a systemic insecticide, flonicamid can control piercing-sucking pests efficiently. In our study, the lethal effects of flonicamid on the biological traits of R. padi were investigated via a life table approach. Flonicamid is highly efficiently toxic to R. padi, with an LC50 of 9.068 mg L−1. The adult longevity and fecundity of the R. padi F0 generation were markedly reduced under the LC25 and LC50 concentrations of flonicamid exposure. In addition, negative transgenerational effects on R. padi were observed under exposure to lethal concentrations of flonicamid, with noticeable decreases in the reproductive period, adult longevity, total longevity, and total fecundity of the F1 generation under the LC25 concentration of flonicamid. Furthermore, the third nymph stage (N3), preadult stage, duration of the adult pre-reproductive period, duration of the total pre-reproductive period, reproductive period, adult longevity, total longevity, and total fecundity of the F1 generation were significantly lower under treatment with the LC50 concentration of flonicamid. The life table parameters were subsequently analysed, revealing that the intrinsic rate of increase (rm) and the net reproductive rate (R0) were significantly lower but that the finite rate of increase (λ) and the mean generation time (T) were not significantly different under the LC25 and LC50 concentrations of flonicamid. These data are beneficial for grain aphid control and are critical for exploring the role of flonicamid in the integrated management of this key pest.

In this work, the Riemann–Hilbert (RH) problem is employed to study the multiple high-order pole solutions of the cubic Camassa–Holm (cCH) equation with the term characterizing the effect of linear dispersion under zero boundary conditions and nonzero boundary conditions. Under the reflectionless situation, we generalize the residue theorem and obtain the multiple high-order pole solutions of cCH equation by solving an algebraic system. During the process of establishing the solution of RH problem, to simplify the calculations involving the implicitly expressed of variables (x, t) in the solution, we introduce a new scale (y, t) to ensure the solution of RH problem is explicitly expressed with respect to it. Finally, the exact solutions are obtained for cases involving one high-order pole and N high-order poles.

Varicella is a vaccine-preventable infectious disease. Since 1 December 2018, the varicella vaccine has been included in the local Expanded Programme on Immunization (EPI) in Wuxi, China, and children born after 1 December 2014 are eligible for free vaccination. To evaluate the effect of varicella vaccination in Wuxi city, we selected 382 397 children born from 2012 to 2016 as subjects. Their disease data were obtained from the Chinese Disease Prevention and Control Information System, and their vaccination data were obtained from the Jiangsu Province Vaccination Integrated Service Management Information System. The incidence of breakthrough varicella cases increased in the first 4 years and reached the peak in the fifth year. With the increase of vaccination rate, the incidence of varicella decreased significantly. The vaccine effectiveness (VE) was found to be 88.17%–95.78% for one dose and 98.65%–99.93% for two doses. Although the VE per dose decreased from 99.57% in the first year to 93.04% in the eighth year, it remained high. These findings confirmed the effectiveness of varicella vaccination in children, supported the use of a two-dose varicella vaccination strategy to achieve better protection, and provided important insights into the optimal vaccination strategy for varicella prevention in children.

Numerous studies have indicated that turbulence typically initiates along the boundary layer of the stationary disk within a rotor–stator cavity. To describe the transition process to turbulence on the stationary side of a closed rotor–stator cavity, a comprehensive approach combining global linear stability analysis with direct numerical simulation was adopted in the present study. The proposed model aligns with that of Yim et al. (J. Fluid Mech., vol. 848, 2018, pp. 631–647), who investigated the stability characteristics of the rotating-disk boundary layer in a rotor–stator cavity. In order to achieve a stable inflow for the stationary-disk boundary layer, we rotate the shroud together with the rotating disk. Through careful global stability analysis, the predominant spiral mode exhibiting the highest instability in the boundary layer of the stationary disk was discerned, corroborating observations from simulations. Initially, the spiral mode undergoes linear amplification, reaches a state of linear saturation and enters the nonlinear regime. Following nonlinear saturation in the flow field, a circular wave mode arises due to the influence of mean flow distortion. As the Reynolds number attained a sufficiently high level, the interplay between the downstream-propagating circular mode and spiral mode amplified disturbances in the boundary layer of the stationary disk, ultimately leading to the development of localised turbulence at the mid-radius of the rotor–stator cavity. Notably, the present study is the first to elucidate the coexistence of laminar–transitional–turbulent flow states in the stationary-disk boundary layer through direct numerical simulations.

The social-sexual environment is well known for its influence on the survival of organisms by modulating their reproductive output. However, whether it affects survival indirectly through a variety of cues without physical contact and its influence relative to direct interaction remain largely unknown. In this study, we investigated both the indirect and direct influences of the social-sexual environment on the survival and reproduction of the mite Tyrophagus curvipenis (Acari: Acaridae). The results demonstrated no apparent influence of conspecific cues on the survival of mites, but the survival and reproduction of mated female mites significantly changed, with the females mated with males having a significantly shortened lifespan and increased lifetime fecundity. For males, no significant difference was observed across treatments in their survival and lifespan. These findings indicate that direct interaction with the opposite sex has a much more profound influence on mites than indirect interaction and highlight the urgent need to expand research on how conspecific cues modulate the performance of organisms with more species to clarify their impacts across taxa.

For the launch vehicle attitude control problem, traditional methods can seldom accurately identify the fault types, making the control method lack of pertinence, which largely affects the effect of attitude control. This paper proposes an active fault tolerant control strategy, which mainly includes fault diagnosis and fault tolerant control. In the fault diagnosis part, a small deviation attitude dynamics model of the launch vehicle is established, Kalman filters with different structures are designed to detect and isolate faults through residual changes, and the fault quantity of the actuator is further estimated. In the fault tolerant control part, the following control scheme is adopted according to the above diagnostic information: when the sensor fault is detected, the sensor measurement data is reconstructed; when the actuator fault is identified, the control allocation matrix is reconstructed. Simulation results show that the proposed method can effectively diagnose sensor fault and actuator faults, and significantly improve attitude tracking accuracy and control adjustment time.

We report how artificial nests can be utilised at scale in nest site-limited areas of Mongolia to create a managed population of Saker Falcons (Falco cherrug), an “Endangered” species that is harvested for international trade. The provision of 5,000 artificial nests created an average annual saker population of 602 (SE ± 59) breeding pairs, producing an estimated 1,735 (SE ± 272) fledglings per annum over the period 2013–2015. Our regular monitoring enabled us to identify the effects of climate and vegetation on breeding performance. A warm and dry climate prior to breeding was associated with earlier egg-laying dates, while warmer conditions during the breeding season increased fledging success. Greater vegetation biomass in the previous growth season was positively related to breeding density and earlier clutch initiation, which was associated with larger clutch size and larger fledged brood size. Furthermore, using small mammal remains from saker pellets collected at artificial nest sites, we found that higher breeding density, earlier egg laying, larger clutch size, and increased nest survival were associated with areas with a higher proportion of small mammal prey in the diet. Our results provided evidence of the role of temporal and spatial variation in climate and prey availability on breeding performance, demonstrating the requirement for dynamic modelling of variable demographic parameters to be incorporated within an adaptive management framework for the sustainable management of the Saker Falcon.

With the development of high-power microwave technology, the output power of the pulse generator is required more and more higher. In this paper, it is realized by increasing the output power of the module while the output impedance of the module changes little. The module of the generator is based on pulse forming network (PFN) and linear transformer (LT). Four Blumlein PFNs with arc-type configuration and 24 Ω characteristic impedance were connected symmetrically to the primary coil of the LTD and driven by two identical laser triggered spark switches to ensure four Blumlein PFNs synchronizing operation. On this basis, a two-stage high-power pulse generator based on PFN-LT is developed. The following technical parameters of the generator were achieved on a 12 Ω high-power solid resistor: output voltage amplitude of ∼250 kV and output power of ∼5.2 GW at a repetition rate of 5 Hz.

Increasing evidence shows that maternal hyperglycemia inhibits cardiomyocyte (CM) proliferation and promotes cell apoptosis during fetal heart development, which leads to cardiac dysplasia. Accumulating evidence suggests that the overexpression of miR-21 in CMs has a protective role in cardiac function. Therefore, we investigated whether miR-21 can rescue CM injury caused by high glucose. First, we performed biological function analysis of miR-21-5p overexpression in H9c2 cells treated with high glucose. We found that the proliferation of H9c2 cells treated with high glucose decreased significantly and was rescued after overexpression of miR-21-5p. CCK-8 and EdU incorporation assays were performed to assess cell proliferation. The cell proliferation of the miR-21-5p mimic transfection group was improved compared with that of the NC mimic group (*p < 0.05, miR-21-5p mimics vs. NC mimics) when the proliferation of H9c2 cells was reduced by high glucose (****p < 0.0001, high glucose (HG) vs. normal glucose (NG)). Then, we verified the targeted and negative regulation of miR-21-5p on Rhob using a dual-luciferase activity assay and RT-qPCR, respectively. We further demonstrated that miR-21-5p regulates Rhob to rescue the inhibition of CM proliferation induced by high glucose. The CCK-8 results showed that the cell proliferation of the siRNA-Rhob group was higher than that of the NC mimic group (***p < 0.001) and that of the cotransfection group with Up-Rhob plasmids and miR-21-5p mimics was lower than that of the miR-21-5p mimic group (*p < 0.05). Conclusion: Overexpression of miR-21-5p rescues the inhibition of high glucose-induced CM proliferation through regulation of Rhob.

Fine mapping and discovery of watermelon rind trait candidate genes are of great significance for modern watermelon breeding and development. In this study, we used the high-resolution genetic mapping and genome-wide genetic variation detection technology, combined with genome survey and sequencing technology, to locate and discover the candidate genes for rind traits of star watermelon varieties ‘Su XuanBai’ and ‘SHLX21’. Firstly, we identified a total of eight quantitative trait loci (QTLs) related to watermelon rind traits on chromosome 6. Secondly, a total of 208,240 single nucleotide polymorphisms and 75,345 small Indels (insertions/deletions) were detected in the two parents by high-coverage re-sequencing, respectively. Based on the genetic variation of the two parents and combined with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using the planta database, the QTL region was reduced to 0.02 Mb. Finally, we identified the six potential regulatory factors for watermelon rind traits using real-time quantitative PCR. In conclusion, our results revealed the fine localization of candidate genes for watermelon rind traits and the successful discovery of candidate genes for regulating watermelon rind traits, which is of importance for watermelon rind traits and breeding-improved watermelon varieties.