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.

Acoustic resonances in cascade structures may cause structural damage and instability problems in aero-engines and other industrial plants; thus, developing corresponding prediction methods is important. However, works published in the open literature mostly focus on the special case of the stationary Parker modes and provide little knowledge into the rotating resonances in annular cascades, especially in the presence of non-zero background mean flows. This paper develops a three-dimensional semi-analytic model to study the acoustic resonances in an annular cascade in the presence of axial mean flow. The model applies an unsteady cascade response based on the three-dimensional lifting surface method to construct a matrix equation. Characteristic frequencies are solved in the complex domain by numerically searching for singular points. Both the oscillation frequency and the growth rate of the three-dimensional resonance modes are theoretically calculated for the first time under non-zero mean flow conditions. The results reveal an organised distribution with varying inter-blade phase angle and show obvious change with the background flow speed. It is found that the unsteady vortex shedding from the trailing edges of the cascade is a key factor influencing the dissipation rate of the resonance modes. In addition, the important effects of acoustic scattering by the cascade during resonances are examined, which qualitatively corroborate some previous experimental observations.

Based on a 4f system, a 0° reflector and a single laser diode side-pump amplifier, a new amplifier is designed to compensate the spherical aberration of the amplified laser generated by a single laser diode side-pump amplifier and enhance the power of the amplified laser. Furthermore, the role of the 4f system in the passive spherical aberration compensation and its effect on the amplified laser are discussed in detail. The results indicate that the amplification efficiency is enhanced by incorporating a 4f system in a double-pass amplifier and placing a 0° reflector only at the focal point of the single-pass amplified laser. This method also effectively uses the heat from the gain medium (neodymium-doped yttrium aluminium garnet) of the amplifier to compensate the spherical aberration of the amplified laser.

Artificial intelligence (AI) has been recently applied to different mental health illnesses and healthcare domains. This systematic review presents the application of AI in mental health in the domains of diagnosis, monitoring, and intervention. A database search (CCTR, CINAHL, PsycINFO, PubMed, and Scopus) was conducted from inception to February 2024, and a total of 85 relevant studies were included according to preestablished inclusion criteria. The AI methods most frequently used were support vector machine and random forest for diagnosis, machine learning for monitoring, and AI chatbot for intervention. AI tools appeared to be accurate in detecting, classifying, and predicting the risk of mental health conditions as well as predicting treatment response and monitoring the ongoing prognosis of mental health disorders. Future directions should focus on developing more diverse and robust datasets and on enhancing the transparency and interpretability of AI models to improve clinical practice.

This study aims to investigate the effects of the vine of Lonicera japonica Thunb (VLT) and marine-derived Bacillus amyloliquefaciens-9 (BA-9) supplementation on the growth performance, antioxidant capacity, and gut microbiota of goat kids. A total of 32 4-week-old kids were randomly assigned into four groups: a control group (CON), a group supplemented with 0.3% BA-9 (BA-9), a group supplemented with 2% VLT (VLT), and a group supplemented with both 0.3% BA-9 and 2% VLT (MIX). The results indicated that VLT supplementation significantly increased both average daily (P < 0.001) and total weight gain (TWG) (P < 0.001), while BA-9 alone had no significant effect (P > 0.05) on the average daily and TWG. Biomarker analysis of oxidative stress revealed that supplementation of VLT or BA-9 alone enhanced antioxidant capacity. The MIX group showing a higher total antioxidant capacity (T-AOC) compared with the CON, VLT, and BA-9 groups (P < 0.05). Plasma albumin (ALB) levels were significantly increased in the both VLT and BA-9 groups. Microbiota analysis revealed significant differences in α-diversity and β-diversity between the MIX and CON groups, with specific genera such as Prevotellaceae_UCG.004 and Rikenellaceae_RC9_gut_group negatively correlated with average daily gain (ADG), while Alistipes was positively correlated with T-AOC. These findings suggest that the combined supplementation of VLT and BA-9 can significantly enhance growth performance and antioxidant capacity in goat kids by modulating the composition of gut microbiota and reducing oxidative stress.

Although dietary factors have been examined as potential risk factors for liver cancer, the evidence is still inconclusive. Using a diet-wide association analysis, our research evaluated the associations of 126 foods and nutrients on the risk of liver cancer in a Chinese population. We obtained the diet consumption of 72,680 women in the Shanghai Women’s Health Study using baseline dietary questionnaires. The association between each food and nutrient and liver cancer risk was quantified by Cox regression model. A false discovery rate of 0.05 was used to determine the foods and nutrients which need to be verified. Totally 256 incident liver cancer cases were identified in 1,267,391 person-years during the follow-up duration. At the statistical significance level (P ≤ 0.05), higher intakes of cooked wheaten foods, pear, grape and copper were inversely associated with liver cancer risk, while spinach, leafy vegetables, eggplant and carrots showed the positive associations. After considering multiple comparisons, no dietary variable was associated with liver cancer risk. Similar findings were seen in the stratification, secondary and sensitivity analyses. Our findings observed no significant association between dietary factors and liver cancer risk after considering multiple comparisons in Chinese women. More evidence is needed to explore the associations between diet and female liver cancer occurrence.

This work investigates the spatio-temporal evolution of coherent structures in the wake of a generic high-speed train, based on a three-dimensional database from large eddy simulation. Spectral proper orthogonal decomposition (SPOD) is used to extract energy spectra and energy ranked empirical modes for both symmetric and antisymmetric components of the fluctuating flow field. The spectrum of the symmetric component shows overall higher energy and more pronounced low-rank behaviour compared with the antisymmetric one. The most dominant symmetric mode features periodic vortex shedding in the near wake, and wave-like structures with constant streamwise wavenumber in the far wake. The mode bispectrum further reveals the dominant role of self-interaction of the symmetric component, leading to first harmonic and subharmonic triads of the fundamental frequency, with remarkable deformation of the mean field. Then, the stability of the three-dimensional wake flow is analysed based on two-dimensional local linear stability analysis combined with a non-parallelism approximation approach. Temporal stability analysis is first performed for both the near-wake and the far-wake regions, showing a more unstable condition in the near-wake region. The absolute frequency of the near-wake eigenmode is determined based on spatio-temporal analysis, then tracked along the streamwise direction to find out the global mode growth rate and frequency, which indicate a marginally stable global mode oscillating at a frequency very close to the most dominant SPOD mode. The global mode wavemaker is then located, and the structural sensitivity is calculated based on the direct and adjoint modes derived from a local spatial analysis, with the maximum value localized within the recirculation region close to the train tail. Finally, the global mode shape is computed by tracking the most spatially unstable eigenmode in the far wake, and the alignment with the SPOD mode is computed as a function of streamwise location. By combining data-driven and theoretical approaches, the mechanisms of coherent structures in complex wake flows are well identified and isolated.

This study examined the sour grapes/sweet lemons rationalization through 2 conditions: ‘attainable’ (sweet lemons) and ‘unattainable’ (sour grapes), reflecting China’s 2019-nCoV vaccination strategy. The aim was to find ways to change people’s beliefs and preferences regarding vaccines by easing their safety concerns and encouraging more willingness to get vaccinated. An online survey was conducted from January 22 to 27, 2021, with 3,123 residents across 30 provinces and municipalities in the Chinese mainland. The direction of belief and preference changed in line with the sour grapes/sweet lemons rationalization. Using hypothetical and real contrasts, we compared those for whom the vaccine was relatively unattainable (‘sour grapes’ condition) with those who could get the vaccine easily (‘sweet lemons’). Whether the vaccine was attainable was determined in the early stage of the vaccine roll-out by membership in a select group of workers that was supposed to be vaccinated to the greatest extent possible, or, by being in the second stage when the vaccine was available to all. The attainable conditions demonstrated higher evaluation in vaccine safety, higher willingness to be vaccinated, and lower willingness to wait and see. Hence, we propose that the manipulation of vaccine attainability, which formed the basis of the application of sour grapes/sweet lemons rationalization, can be utilized as a means to manipulate the choice architecture to nudge individuals to ease vaccine safety concerns, reducing wait-and-see tendencies, and enhancing vaccination willingness. This approach can expedite universal vaccination and its associated benefits in future scenarios resembling the 2019-nCoV vaccine rollout.

A high-energy picosecond 355 nm ultraviolet (UV) laser operating at 100 Hz was demonstrated. A 352 mJ, 69 ps, 1064 nm laser at 100 Hz was realized firstly by cascaded regenerative, laser diode end-pumped single-pass and side-pumped main amplifiers. The stimulated Raman scattering-based beam shaping technique, thermally induced birefringence compensation and 4f spatial filter-image relaying systems were used to maintain a relatively homogeneous beam intensity distribution during the amplification process. By using lithium triborate crystals for second- and third-harmonic generation (THG), a 172 mJ, approximately 56 ps, 355 nm UV laser was achieved with a THG conversion efficiency of 49%. To the best of our knowledge, it is the highest pulse energy of a picosecond 355 nm UV laser so far. The beam quality factor ${M}^2$ and pulse energy stability were ${M}_x^2$=3.92, ${M}_y^2$=3.71 and root mean square of 1.48%@3 hours. This laser system could play significant roles in applications including photoconductive switch excitation, laser drilling and laser micro-fabrication.

This study investigates the molecular intricacies of the transmembrane protein TSP11 gene in Echinococcus strains isolated from livestock and patients in Yunnan Province afflicted with Echinococcus granulosus (E. granulosus) between 2016 and 2020. Gene typing analysis of the ND1 gene revealed the presence of the G1 type, G5 type and untyped strains, constituting 52.4, 38.1 and 9.5%, respectively. The analysis of 42 DNA sequences has revealed 24 novel single nucleotide polymorphic sites, delineating 11 haplotypes, all of which were of the mutant type. Importantly, there were no variations observed in mutation sites or haplotypes in any of the hosts. The total length of the TSP11 gene's 4 exons is 762 bp, encoding 254 amino acids. Our analysis posits the existence of 6 potential B-cell antigenic epitopes within TSP11, specifically at positions 49-KSN-51, 139-GKRG-142, 162-DNG-164, 169-NGS-171, 185-DS-186 and 231-PPRFTN-236. Notably, these epitopes exhibit consistent presence among various intermediate hosts and haplotypes. However, further validation is imperative to ascertain their viability as diagnostic antigens for E. granulosus in the Yunnan Province.

We analyzed invasive group A streptococcal puerperal sepsis cases in a large health zone in Alberta, Canada between 2013 and 2022. Of the 21 cases, 85.7% were adjudicated as hospital/delivery-acquired, with 2 clusters having identical isolates found through whole genome sequencing. We implemented policy interventions across Alberta aimed at preventing future infections.