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.

This paper presents an innovative eight-pass laser amplifier design that effectively utilizes polarization and angular multiplexing, enjoying high gain, high extraction efficiency and compact layout. To optimize the design parameters, a general spatiotemporal model for a multi-pass amplifier is established that accounts for beam passages in different angles, and the predicted output energy and gain distribution agree well with the experimental results. The multi-pass amplifier scales the seed energy of 120 mJ to 5 J at 10 Hz and 3 J at 50 Hz, with the beam quality within three times the diffraction limit.

Radiocarbon (14C) measurements play important roles in dating and tracing applications where the isotopic concentration can differ from 0.1 to 106 pMC (percent modern carbon). A liquid scintillation counter cannot provide enough sensitivity when dealing with low-concentration samples of limited amounts over a reasonable time period. Accelerator mass spectroscopy (AMS) measures low-concentrations well but must first do dilution for high-concentration samples, and suffers from high instrument and maintenance costs. Saturated absorption CAvity Ring-down spectroscopy (SCAR) has now been developed into a practical technique with performances close to AMS but at much lower costs. The dynamic range covers 1–105 pMC, and the measurement uncertainties in the range of 0.4–1 pMC can be achieved within 0.5–2.5 hr of operation time. SCAR measures CO2 gases directly without graphitization in sample preparation. The typical sample consumption is ∼1 mg of carbon mass and the time for sample preparation can be as short as 15 min. Applications of SCAR to Suess-effect evaluation, biogenic-component analysis, ancient- and modern-sample dating, food-fraud detection and medicine-metabolism study have all been demonstrated by employing a close-to-automatic sample preparation system.

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.

Predicting epidemic trends of coronavirus disease 2019 (COVID-19) remains a key public health concern globally today. However, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rate in previous studies of the transmission dynamics model was mostly a fixed value. Therefore, we proposed a meta-Susceptible-Exposed-Infectious-Recovered-Susceptible (SEIRS) model by adding a time-varying SARS-CoV-2 reinfection rate to the transmission dynamics model to more accurately characterize the changes in the number of infected persons. The time-varying reinfection rate was estimated using random-effect multivariate meta-regression based on published literature reports of SARS-CoV-2 reinfection rates. The meta-SEIRS model was constructed to predict the epidemic trend of COVID-19 from February to December 2023 in Sichuan province. Finally, according to the online questionnaire survey, the SARS-CoV-2 infection rate at the end of December 2022 in Sichuan province was 82.45%. The time-varying effective reproduction number in Sichuan province had two peaks from July to December 2022, with a maximum peak value of about 15. The prediction results based on the meta-SEIRS model showed that the highest peak of the second wave of COVID-19 in Sichuan province would be in late May 2023. The number of new infections per day at the peak would be up to 2.6 million. We constructed a meta-SEIRS model to predict the epidemic trend of COVID-19 in Sichuan province, which was consistent with the trend of SARS-CoV-2 positivity in China. Therefore, a meta-SEIRS model parameterized based on evidence-based data can be more relevant to the actual situation and thus more accurately predict future trends in the number of infections.

Tea is one of the most widely consumed beverages in the world. However, the association between tea and risk of pancreatic adenocarcinoma remains controversial. This study aimed to investigate the causal relationship between tea consumption and risk of pancreatic adenocarcinoma and to explore their mediating effects. The two-sample Mendelian randomisation (MR) analysis showed an inverse causal relationship between tea intake and pancreatic adenocarcinoma (OR: 0·111 (0·02, 0·85), P < 0·04). To examine the mediating effects, we explored the potential mechanisms by which tea intake reduces the risk of pancreatic adenocarcinoma. Based on the oral bioavailability and drug-like properties in Traditional Chinese Medicine Systems Pharmacology database, we selected the main active ingredients of tea. We screened out the fifteen representative targeted genes by Pharmmapper database, and the gene ontology enrichment analysis showed that these targeted genes were related to vascular endothelial growth factor (VEGF) pathway. The two-step MR analysis of results showed that only VEGF-D played a mediating role, with a mediation ratio of 0·230 (0·066, 0·394). In conclusion, the findings suggest that VEGF-D mediates the effect of tea intake on the risk of pancreatic adenocarcinoma.

Fast neutron absorption spectroscopy is widely used in the study of nuclear structure and element analysis. However, due to the traditional neutron source pulse duration being of the order of nanoseconds, it is difficult to obtain a high-resolution absorption spectrum. Thus, we present a method of ultrahigh energy-resolution absorption spectroscopy via a high repetition rate, picosecond duration pulsed neutron source driven by a terawatt laser. The technology of single neutron count is used, which results in easily distinguishing the width of approximately 20 keV at 2 MeV and an asymmetric shape of the neutron absorption peak. The absorption spectroscopy based on a laser neutron source has one order of magnitude higher energy-resolution power than the state-of-the-art traditional neutron sources, which could be of benefit for precisely measuring nuclear structure data.

Animal studies have shown that capsaicin plays a positive role in weight management. However, the results in human research are controversial. Therefore, the present systematic review and meta-analysis aimed to evaluate the effect of capsaicin on weight loss in adults. We searched PubMed, Embase, China Biomedical Literature Database (CBM), Cochrane library and clinical registration centre, identifying all randomised controlled trials (RCT) published in English and Chinese to 3 May 2022. A random-effect model was used to calculate the weighted mean difference (WMD) and 95 % CI. Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests (I2). Statistical analyses were performed using STATA version 15.1. P-values < 0·05 were considered as statistically significant. From 2377 retrieved studies, fifteen studies were finally included in the meta-analyses. Fifteen RCT with 762 individuals were included in our meta-analysis. Compared with the control group, the supplementation of capsaicin resulted in significant reduction on BMI (WMD: −0·25 kg/m2, 95 % CI = –0·35, –0·15 kg/m2, P < 0·05), body weight (BW) (WMD: −0·51 kg, 95 % CI = –0·86, –0·15 kg, P < 0·05) and waist circumference (WC) (WMD: −1·12 cm, 95 % CI = –2·00, –0·24 cm, P < 0·05). We found no detrimental effect of capsaicin on waist-to-hip ratio (WMD: −0·05, 95 % CI = –0·17, 0·06, P > 0·05). The current meta-analysis suggests that capsaicin supplementation may have rather modest effects in reducing BMI, BW and WC for overweight or obese individuals.

Time preference reversal refers to systematic inconsistencies between preferences and bids for intertemporal options. From the two eye-tracking studies (N1 = 60, N2 = 110), we examined the underlying mechanisms of time preference reversal. We replicated the reversal effect in which individuals facing a pair of intertemporal options choose the smaller-sooner option but assign a higher value to the larger-later one. Results revealed that the mean fixation duration and the proportion of gaze time on the outcome attribute varied across the choice and bid tasks. In addition, time preference reversals correlated with individual differences in maximizing tendencies. Findings support the contingent weighting hypothesis and strategy compatibility hypothesis and allow for improved theoretical understanding of the potential mechanisms and processes involved in time preference reversals.

Particle-resolved direct numerical simulations are employed to investigate the particle–particle drag force in the bidisperse gas–particle suspensions where the particles are smooth and the single-particle velocity distribution function is Maxwellian. The particle Reynolds number ranges from 6.7 to 123.8, and in this range the particle inertia is high enough that the lubrication force is not essential. It is found that the relation derived by the kinetic theory of granular flow (KTGF) highly overestimates the particle–particle drag force. This is because the pre-collision velocities of colliding particles are not completely uncorrelated with each other. From the time sequence of collision events, it is observed that the particle pair that has just collided will probably collide again after a short time due to the restriction of the particle motion in dense suspensions. Since the post-collision velocities of the first collision cannot relax entirely in such a short time, the relative velocity before the subsequent collision is statistically smaller than the domain-averaged relative velocity. Consequently, the particle–particle drag force is over-predicted when the domain-averaged relative velocity is used. For this reason, this work assumes that the particle–particle drag force is determined by the relative velocity within a local region near large particles. When the local region is set to be the spherical shells centred on the centres of large particles and with an outer radius of a mean free path of small particles, the KTGF-based relation can reasonably predict the particle–particle drag force.

Inkjet printing, originally invented for text and pattern printing, is now central to many industrial applications, such as printed electronics, flexible electronics, 3-D printing of mechanical and even biological devices. However, constrained by the droplets’ ejection mechanism, the accuracy of traditional inkjet printing is limited by the size of its orifice, and it is difficult to achieve a volume of droplets at the femtolitre scale, which hinders its further application in the above fields. To this end, we propose the confined interface vibration inkjet printing (CIVIJP) technique, which is capable of printing patterns in a liquid environment with droplet size much smaller than the orifice from which they are dispensed. Here, further systematic study of the mechanism of printing in a liquid environment was carried out with the assistance of a high-speed imaging technique. It is found for the first time that a single pulse stimulation applied on the piezo-ceramic of the inkjet nozzle can trigger damping oscillations of the oil/water interface confined by the orifice, which can last more than 500 $\mathrm {\mu }$s. By adjusting the intensity of single pulse stimulation, the size and quantity of the dispensed droplets can be controlled in a wide range, which is obviously different from traditional droplet ejection in a gaseous environment. This work reveals the underlying physics between the pulse stimulation and the interface behaviours, as well as the physics between the interface behaviours and the size and number of dispensed droplets, enriching the fundamental theory of the inkjet printing in liquid phase.

A combined theoretical and experimental investigation is conducted with the objective of evaluating the lift aerodynamic admittances of an airfoil in various turbulent flow fields. Current theoretical approaches and concepts are reviewed and extended, enabling us to use a strategy to measure the one-wavenumber aerodynamic admittance in the turbulent flow field. The key of the strategy is to separate the spanwise effect from the generalized aerodynamic admittances which can be directly determined by the one-dimensional lift spectrum and one-dimensional turbulent velocity spectrum. With this strategy, the experimental values of one-wavenumber aerodynamic admittances of a two-dimensional airfoil with a NACA 0015 profile in three turbulent flow fields are obtained. As expected, due to the influence of the spanwise effect, the generalized aerodynamic admittances vary with different turbulent flow fields, exhibiting a significant dependence on flow field, and are much less than the Sears function. Contrarily, the one-wavenumber aerodynamic admittances, which are obtained in three turbulent flow fields, are generally consistent, confirming that the one-wavenumber aerodynamic admittance is mainly related to the cross-sectional shape itself. The experimental values of one-wavenumber aerodynamic admittances are compared with the Sears function. The results of all cases indicate that the experimental results agree well with the Sears function at low frequencies, while decaying faster at high frequencies.

A droplet impinging on a superhydrophobic substrate in an electric field is an important process in droplet manipulation and electrostatic spraying. Here, the entire impinging dynamic of the droplet in a vertical electric field is studied by a visualization experiment and numerical simulation with OpenFOAM. We investigate the effect of an electrostatic force on droplet impact in depth, where four ejection modes and three rebound modes are found experimentally. In particular, the filamentous ejecting phenomenon occurs after a droplet impinging on a superhydrophobic substrate is first discovered. In the numerical simulation, the strong coupling between the dynamic distribution of the interface electric charge and the evolution of the droplet profile can lead to different ejection modes, and the different ejection behaviours are caused by the combined effects of electrostatic pressure, capillary pressure, dynamic pressure and static pressure on the droplet apex. A charge scaling law for the ejection droplets is proposed. Furthermore, a set of theoretical models is established, which can successfully predict the threshold electric capillary number for different droplet ejection modes. The results reveal some important characteristics for a droplet impinging on a superhydrophobic surface in an electric field, which could facilitate the design of electrically operated droplet equipment and guide the safe and stable operation of the device.

Two new genera and six new species of trilobites are systematically documented herein: Sinagnostus mirabilis new genus new species, Yanpingia punctata n. gen. n. sp., Illaenus taoyuanensis n. sp., Panderia striolatus n. sp., Nileus yichongqiaoensis n. sp., and Paratiresias peculiaris n. sp. The materials were collected from the Darriwilian (late Middle Ordovician) strata in the Upper Yangtze Region, South China. Also provided is an emended diagnosis of the genus Paratiresias based on the new species Paratiresias peculiaris, which is the oldest known species of this genus with an extremely narrow (sag. and exsag.) preglabellar field. Those Chinese species previously referred to Nanillaenus are reassigned to Illaenus sensu lato. These trilobites add new data for the Darriwilian trilobite macroevolution and show highly endemic to South China and the faunal exchanges between South China and Tarim, Kazakhstan, Alborz, as well as Sibumasu and North China.

UUID: http://zoobank.org/ec3be9be-b003-4367-910d-7a0ac4edc982

The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.