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.

To meet the high-precision positioning requirements for hybrid machining units, this article presents a geometric error modeling and source error identification methodology for a serial–parallel hybrid kinematic machining unit (HKMU) with five axis. A minimal kinematic error modeling of the serial–parallel HKMU is established with screw-based method after elimination of redundant errors. A set of composite error indices is formulated to describe the terminal accuracy distribution characteristics in a quantitative manner. A modified projection method is proposed to determine the actual compensable and noncompensable source errors of the HKMU by identifying such transformable source errors. Based on this, the error compensation and comparison analysis are carried out on the exemplary HKMU to numerically verify the effectiveness of the proposed modified projection method. The geometric error evaluations reveal that the parallel module has a larger impacts on the terminal accuracy of the platform of the HKMU than the serial module. The error compensation results manifest that the modified projection method can find additional compensable source errors and significantly reduce the average and maximum values of geometric errors of the HKMU. Hence, the proposed methodology can be applied to improve the accuracy of kinematic calibration of the compensable source errors and can reduce the difficulty and workload of tolerance design for noncompensable source errors of such serial–parallel hybrid mechanism.

Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/β-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/β-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.

A multistep pulse compressor (MPC) based on a single-pass single-grating pair (SSGP) is proposed to simplify the entire multi-petawatt (PW) compressor. Only one grating pair with relatively long perpendicular distance is used to generate the same amount of spectral chirp compared with a four-grating main compressor. As SSGP compressor induces the largest spatial chirp, it can introduce the best beam-smoothing effect to the laser beam on the last grating. When considering the diffraction loss of only two gratings, the total compression efficiency of the SSGP compressor is even larger than that of a four-grating main compressor. Furthermore, the wavefront aberration induced by the SSGP compressor can be better compensated by using deformable mirrors; however, it is difficult or complicated to be well compensated in a four-grating compressor. Approximately 50–100 PW laser pulses can be obtained using this SSGP-based multistage-smoothing MPC with a single laser beam.

Evidence of couples’ BMI and its influence on birth weight is limited and contradictory. Therefore, this study aims to assess the association between couple’s preconception BMI and the risk of small for gestational age (SGA)/large for gestational age (LGA) infant, among over 4·7 million couples in a retrospective cohort study based on the National Free Pre-pregnancy Checkups Project between 1 December 2013 and 30 November 2016 in China. Among the live births, 256 718 (5·44 %) SGA events and 506 495 (10·73 %) LGA events were documented, respectively. After adjusting for confounders, underweight men had significantly higher risk (OR 1·17 (95 % CI 1·15, 1·19)) of SGA infants compared with men with normal BMI, while a significant and increased risk of LGA infants was obtained for overweight and obese men (OR 1·08 (95 % CI 1·06, 1·09); OR 1·19 (95 % CI 1·17, 1·20)), respectively. The restricted cubic spline result revealed a non-linear decreasing dose–response relationship of paternal BMI (less than 22·64) with SGA. Meanwhile, a non-linear increasing dose–response relationship of paternal BMI (more than 22·92) with LGA infants was observed. Moreover, similar results about the association between maternal preconception BMI and SGA/LGA infants were obtained. Abnormal preconception BMI in either women or men were associated with increased risk of SGA/LGA infants, respectively. Overall, couple’s abnormal weight before pregnancy may be an important preventable risk factor for SGA/LGA infants.

As an attractive collector medium for hypervelocity particles, combined with outstanding physical properties and suitable compositional characteristics, SiO2 aerogel has been deployed on outer space missions and laser shock-loaded collection experiments. In this paper, impact experiments were conducted to understand the penetration process of irregular grains, irregular Al2O3 grains with two different sizes and speeds (~110 μm@7 km/s, ~251 μm@2.3 km/s) at various density silica aerogels. By classifying the shapes of projectile residues and tracks, the morphology of tracks was analyzed. It was observed that there were several kinds of typical tracks in the penetration of irregular grains, accompanied by residues with the shapes of near-sphere, polyhedron, streamlined body wedge, and rotator. The rotational behavior was demonstrated by the final status of one flake projectile as direct evidence. In addition, there was no obvious relationship between the track length and experimental parameters, which may be caused by the uncertain interaction between aerogels and irregular particles. In addition, it confirmed the existence of fragmentation, melting situation by observing the shape of the impact entrance hole. At the same time, optical coherence tomography was used to observe the detail of tracks clearly, which provided a method to characterize the tracks nondestructively.

Anaemia is a global public health problem affecting women worldwide, and reproductive-age women are at increased risk. We conducted a population-based cross-sectional study analysing the prevalence of overall anaemia and anaemia according to severity in Chinese pre-pregnant women to update current knowledge on anaemia epidemiology. Based on the National Free Preconception Check-up Projects supported by the Chinese government, 5 679 782 women participating in this project in 2017 were included in the present study. The cyanmethemoglobin method was applied to assess Hb concentrations. Univariate and multivariate logistic regressions were applied for associated factors. The prevalence of anaemia among Chinese pre-pregnant women was 21·64 % (mild: 14·10 %, moderate: 7·17 % and severe : 0·37 %). The prevalence of overall and severe anaemia was the highest in Tibet and the lowest in Beijing among thirty-one provinces. Women’s age, region, ethnic origin, educational level, occupation and pregnancy history were all correlated with anaemia. Women with B blood type (adjusted OR (aOR) = 0·89), higher BMI (overweight: aOR = 0·84; obesity: aOR = 0·70) and alcohol consumption (aOR = 0·69) were less likely to have anaemia, while those with rhesus negative blood type (aOR = 1·10), history of anaemia (aOR = 2·60), older age at menarche (aOR = 1·19), heavy menstrual blood loss (aOR = 1·39), longer menstrual period (aOR = 1·09) and shorter menstrual cycle (aOR = 1·08) were more likely to suffer from anaemia. Meat or egg eaters were not significantly associated with severe anaemia. Anaemia is of moderate public health significance among Chinese pre-pregnant women. Interventions should be considered to prevent anaemia to the greatest extent possible to avoid potential harm in this population.

Spatial profiles of impurity emission measurements in the extreme ultraviolet (EUV) spectroscopic range in radiofrequency (RF)-heated discharges are combined with one-dimensional and three-dimensional transport simulations to study the effects of resonant magnetic perturbations (RMPs) on core impurity accumulation at EAST. The amount of impurity line emission mitigation by RMPs appears to be correlated with the ion Z for lithium, carbon, iron and tungsten monitored, i.e. stronger suppression of accumulation for heavier ions. The targeted effect on the most detrimental high-Z impurities suggests a possible advantage using RMPs for impurity control. Profiles of transport coefficients are calculated with the STRAHL one-dimensional impurity transport code, keeping $\nu /D$ fixed and using the measured spatial profiles of $\textrm{F}{\textrm{e}^{20 + }}$, $\textrm{F}{\textrm{e}^{21 + }}$ and $\textrm{F}{\textrm{e}^{22 + }}$ to disentangle the transport coefficients. The iron diffusion coefficient ${D_{\textrm{Fe}}}$ increases from $1.0- 2.0\;{\textrm{m}^2}\;{\textrm{s}^{ - 1}}$ to $1.5- 3.0\;{\textrm{m}^2}\;{\textrm{s}^{ - 1}}$ from the core region to the edge region $(\rho \gt 0.5)$ after the onset of RMPs. Meanwhile, an inward pinch of iron convective velocity ${\nu _{\textrm{Fe}}}$ decreases in magnitude in the inner core region and increases significantly in the outer confined region, simultaneously contributing to preserving centrally peaked $\textrm{Fe}$ profiles and exhausting the impurities. The ${D_{\textrm{Fe}}}$ and ${\nu _{\textrm{Fe}}}$ variations lead to reduced impurity contents in the plasma. The three-dimensional edge impurity transport code EMC3-EIRENE was also applied for a case of RMP-mitigated high-Z accumulation at EAST and compared to that of low-Z carbon. The exhaust of ${\textrm{C}^{6 + }}$ toward the scrape-off layer accompanying an overall suppression of heavier ${\textrm{W}^{30 + }}$ is observed when using RMPs.

We report on a high-power Ho:YAG single-crystal fiber (SCF) laser inband pumped by a high-brightness Tm-fiber laser at 1908 nm. The Ho:YAG SCF grown by the micro-pulling-down technique exhibits a propagation loss of $0.05\pm 0.005~\text{cm}^{-1}$ at $2.09~\unicode[STIX]{x03BC}\text{m}$. A continuous-wave output power of 35.2 W is achieved with a slope efficiency of 42.7%, which is to the best of our knowledge the highest power ever reported from an SCF-based laser in the 2 $\unicode[STIX]{x03BC}\text{m}$ spectral range.

Iodine intake and excretion vary widely; however, these variations remain a large source of geometric uncertainty. The present study aims to analyse variations in iodine intake and excretion and provide implications for sampling in studies of individuals or populations. Twenty-four healthy women volunteers were recruited for a 12-d sampling period during the 4-week experiment. The duplicate-portion technique was used to measure iodine intake, while 24-h urine was collected to estimate iodine excretion. The mean intra-individual variations in iodine intake, 24-h UIE (24-h urinary iodine excretion) and 24-h UIC (24-h urinary iodine concentration) were 63, 48 and 55 %, respectively, while the inter-individual variations for these parameters were 14, 24 and 32 %, respectively. For 95 % confidence, approximately 500 diet samples or 24-h urine samples should be taken from an individual to estimate their iodine intake or iodine status at a precision range of ±5%. Obtaining a precision range of ±5% in a population would require twenty-five diet samples or 150 24-h urine samples. The intra-individual variations in iodine intake and excretion were higher than the inter-individual variations, which indicates the need for more samples in a study on individual participants.

The star formation history (SFH) of galaxies allow us to investigate when galaxies formed their stars and assembled their mass. We can constrain the SFH with high level of precision from galaxies with resolved stellar populations, since we are able to discriminate between stars of different ages from the spectrum they emit. However, the relative importance of secular evolution (nature) over nurture is not yet clear, and separating the effects of interaction-driven evolution in the observed galaxy properties is not trivial. The aim of this study is to use MaNGA (Mapping Nearby Galaxies at APO) Integral Field Unit (IFU) data, in combination with multi-wavelength data, to constrain the SFH of nearby isolated galaxies. We present here the new techniques we are developing to constrain the SFH with high level of precision from Spectral Energy Distribution (SED) fitting. This study is part of a China-Chile collaboration program where we are applying these new techniques to investigate how galaxies formed and evolve in different environments.

The derivation of accurate stellar populations of galaxies is a non-trivial task because of the well-known age-metallicity degeneracy. We aim to break this degeneracy by invoking a chemical evolution model (CEM) for isolated disk galaxy, where its metallicity enrichment history (MEH) is modelled to be tightly linked to its star formation history (SFH). Our CEM has been successfully tested on several local group dwarf galaxies whose SFHs and MEHs have been both independently measured from deep colour-magnitude diagrams of individual stars. By introducing the CEM into the stellar population fitting algorithm as a prior, we expect that the SFH of galaxies could be better constrained.

Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a major cause of community-acquired pneumonia in China. Data on epidemiology of paediatric MPP from China are little known. This study retrospectively collected data from June 2006 to June 2016 in Beijing Children's Hospital, Capital Medical University of North China and aims to explore the epidemiological features of paediatric MPP and severe MPP (SMPP) in North China during the past 10 years. A total of 27 498 paediatric patients with pneumonia were enrolled. Among them, 37.5% of paediatric patients had MPP. In this area, an epidemic took place every 2–3 years at the peak, and the positive rate of MPP increased during these peak years over time. The peak age of MPP was between the ages of 6 and 10 years, accounting for 75.2%, significantly more compared with other age groups (χ2 = 1384.1, P < 0.0001). The epidemics peaked in September, October and November (χ2 = 904.9, P < 0.0001). Additionally, 13.0% of MPP paediatric patients were SMPP, but over time, the rate of SMPP increased, reaching 42.6% in 2016. The mean age of paediatric patients with SMPP (6.7 ± 3.0 years old) was younger than that of patients with non-SMPP (7.4 ± 3.2 years old) (t = 3.60, P = 0.0001). The prevalence of MPP and SMPP is common in China, especially in children from 6 to 10 years old. Paediatric patients with SMPP tend to be younger than those with non-SMPP. MPP outbreaks occur every 2–3 years in North China. September, October and November are the peak months, unlike in South China. Understanding the epidemiological characteristics of paediatric MPP can contribute to timely treatment and diagnosis, and may improve the prognosis of children with SMPP.

Underground Nuclear Astrophysics in China (JUNA) will take the advantage of the ultra-low background in Jinping underground lab. High current accelerator with an ECR source and detectors were commissioned. JUNA plans to study directly a number of nuclear reactions important to hydrostatic stellar evolution at their relevant stellar energies. At the first period, JUNA aims at the direct measurements of 25Mg(p,γ)26 Al, 19F(p,α) 16 O, 13C(α, n) 16O and 12C(α,γ) 16O near the Gamow window. The current progress of JUNA will be given.

Let $\mathbf{M}=(M_{1},\ldots ,M_{k})$ be a tuple of real $d\times d$ matrices. Under certain irreducibility assumptions, we give checkable criteria for deciding whether $\mathbf{M}$ possesses the following property: there exist two constants $\unicode[STIX]{x1D706}\in \mathbb{R}$ and $C>0$ such that for any $n\in \mathbb{N}$ and any $i_{1},\ldots ,i_{n}\in \{1,\ldots ,k\}$, either $M_{i_{1}}\cdots M_{i_{n}}=\mathbf{0}$ or $C^{-1}e^{\unicode[STIX]{x1D706}n}\leq \Vert M_{i_{1}}\cdots M_{i_{n}}\Vert \leq Ce^{\unicode[STIX]{x1D706}n}$, where $\Vert \cdot \Vert$ is a matrix norm. The proof is based on symbolic dynamics and the thermodynamic formalism for matrix products. As applications, we are able to check the absolute continuity of a class of overlapping self-similar measures on $\mathbb{R}$, the absolute continuity of certain self-affine measures in $\mathbb{R}^{d}$ and the dimensional regularity of a class of sofic affine-invariant sets in the plane.