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.

Spatial intensity modulation in amplified laser beams, particularly hot spots, critically constrains attainable pulse peak power due to the damage threshold limitations of four-grating compressors. This study demonstrates that the double-smoothing grating compressor (DSGC) configuration effectively suppresses modulation through directional beam smoothing. Our systematic investigation validated the double-smoothing effect through numerical simulations and experimental measurements, with comprehensive spatiotemporal analysis revealing excellent agreement between numerical and practical pulse characteristics. Crucially, the DSGC enables a 1.74 times energy output boost compared to conventional compressors. These findings establish the DSGC as a pivotal advancement for next-generation ultrahigh-power laser systems, providing a viable pathway toward hundreds of PW output through optimized spatial energy redistribution.

Childhood maltreatment, a significant distal risk factor for individual development, is potentially linked to maladaptive cognitive emotion regulation strategies (MCERS) and increased internalizing problems (i.e., depression and anxiety). Prior research has widely identified that MCERS mediate the link between childhood maltreatment and internalizing problems. However, this result overlooks the potential bidirectional relationship between MCERS and internalizing problems. In this study, we aim to explore whether childhood maltreatment longitudinally linked to internalizing problems through the mediating role of MCERS, or, conversely, was related to subsequent MCERS through internalizing problems. Gender differences in the associations between these variables were also examined. Participants were 892 adolescents from a longitudinal design with two waves (487 females, 405 males; Mage = 15.36, SDage = 1.43). Our results indicated that childhood maltreatment was longitudinally related to MCERS and internalizing problems. T1 MCERS mediated the relationship between T1 child maltreatment and T2 internalizing problems, while T1 internalizing problems also played a mediating role between T1 child maltreatment and T2 MCERS. These findings were also equivalent across genders. Taken together, childhood maltreatment was longitudinally associated with internalizing problems through MCERS, and also related to subsequent MCERS through internalizing problems.

The AIMTB rapid test assay is an emerging test, which adopted a fluorescence immunochromatographic assay to measure interferon-γ (IFN-γ) production following stimulation of effector memory T cells in whole blood by mycobacterial proteins. The aim of this article was to explore the ability of AIMTB rapid test assay in detecting Mycobacterium tuberculosis (MTB) infection compared with the widely applied QuantiFERON-TB Gold Plus (QFT-Plus) test among rural doctors in China. In total, 511 participants were included in the survey. The concordance between the QFT-Plus test and the AIMTB rapid test assay was 94.47% with a Cohen’s kappa coefficient (κ) of 0.84 (95% CI, 0.79–0.90). Improved concordance between the two tests was observed in males and in participants with 26 or more years of service as rural doctors. The quantitative values of the QFT-Plus test was higher in individuals with a result of QFT-Plus-/AIMTB+ as compared to those with a result of QFT-Plus-/AIMTB- (p < 0.001). Overall, our study found that there was an excellent consistency between the AIMTB rapid test assay and the QFT-Plus test in a Chinese population. As the AIMTB rapid test assay is fast and easy to operate, it has the potential to improve latent tuberculosis infection testing and treatment at the community level in resource-limited settings.

Two thrips, Megalurothrips usitatus (Bagnall) and Frankliniella intonsa (Trybom) are major pests of cowpea in South China. To realistically compare the growth, development and reproductive characteristics of these two thrips species, we compared their age-stage, two-sex life tables on cowpea pods under summer and winter natural environmental regimes. The results showed that the total preadult period of M. usitatus was 8.09 days, which was significantly longer than that of F. intonsa (7.06 days), while the adult female longevity of M. usitatus (21.14 days) was significantly shorter than that of F. intonsa (25.77 days). Significant differences were showed in male adult longevity (10.68 days for F. intonsa and 16.95 days for M. usitatus) and the female ratio of offspring (0.67 for F. intonsa and 0.51 for M. usitatus), and the total preadult period of M. usitatus (16.20 days) was significantly longer than that of F. intonsa (13.66 days) in the winter regime. The net reproductive rate (summer: R0 = 85.62, winter: R0 = 105.22), intrinsic rate of increase (summer: r = 0.3020 day−1, winter: r = 0.2115 day−1), finite rate of increase (summer: λ = 1.3526 day−1, winter: λ = 1.2356 day−1) and gross reproduction rate (summer: GRR = 139.34, winter: GRR = 159.88) of F. intonsa were higher than those of M. usitatus (summer: R0 = 82.91, r = 0.2741, λ = 1.3155, GRR = 135.71; winter: R0 = 80.62, r = 0.1672, λ = 1.1820, GRR = 131.26), and the mean generation times (summer: T = 14.73 days, winter: T = 22.01 days) of F. intonsa were significantly shorter than those of M. usitatus (summer: T = 16.11 days, winter: T = 26.25 days). These results may contribute to a better understanding of the bioecology of different thrips species, especially the interspecific competition between two economically important cowpea thrips with the same ecological niche in a changing environment.

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.

An experimental investigation of the stereocamera's systematic error is carried out to optimize three-dimensional (3-D) dust observation on the HL-2A tokamak. It is found that a larger 3-D region occupied by all calibration points is able to reduce the 3-D reconstruction systematic error of the stereocamera. In addition, the 3-D reconstruction is the most accurate around the region where the calibration points are located. Based on these experimental results, the design of the stereocamera on the HL-2A tokamak is presented, and a set of practical procedures to optimize the 3-D reconstruction accuracy of the stereocamera are proposed.

We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.

For individual cultures, findings on regulating embryo density by changing the microdrop volume are contradictory. The aim of this study was to investigate the relationship between embryo density and the developmental outcome of day 3 embryos after adjusting covariates. In total, 1196 embryos from 206 couples who had undergone in vitro fertilization treatment were analyzed retrospectively. Three embryo densities were used routinely, i.e. one embryo in a drop (30 μl/embryo), two embryos in a drop (15 μl/embryo) and three embryos in a drop (10 μl/embryo). Embryo quality on day 3 was evaluated, both the cell number of day 3 embryos and the proportion of successful implantations served as endpoints. Maternal age, paternal age, antral follicles and level of anti-Müllerian hormone, type of infertility, controlled ovarian stimulation protocol, length of stimulation, number of retrieved oocytes, number of zygotes (two pronuclei) and insemination type were covariates and adjusted. After adjusting fully for all covariates, the cell number of day 3 embryos was significantly increased by 0.40 (95% CI 0.00, 0.79; P = 0.048) and 0.78 (95% CI 0.02, 1.54; P = 0.044) in the 15 μl/embryo and 10 μl/embryo group separately, compared with the 30 μl/embryo group. The proportions of implanted embryos were 42.1%, 48.7% and 0.0% in the 30 μl/embryo, 15 μl/embryo and 10 μl/embryo groups respectively. There was no statistical significance (P = 0.22) between the 30 μl/embryo group and the 15 μl/embryo group. After adjusting for confounders that were significant in univariate analysis, embryo density was still not associated with day 3 embryo implantation potential (P > 0.05). In a 30-μl microdrop, culturing embryos with an embryo density of both 15 and 10 μl/embryo increased the cell number of day 3 embryos, which did not benefit embryo implanting potential, compared with individual culture of 30 μl/embryo.

We report on experimental observation of non-laminar proton acceleration modulated by a strong magnetic field in laser irradiating micrometer aluminum targets. The results illustrate the coexistence of ring-like and filamentation structures. We implement the knife edge method into the radiochromic film detector to map the accelerated beams, measuring a source size of 30–110 μm for protons of more than 5 MeV. The diagnosis reveals that the ring-like profile originates from low-energy protons far off the axis whereas the filamentation is from the near-axis high-energy protons, exhibiting non-laminar features. Particle-in-cell simulations reproduced the experimental results, showing that the short-term magnetic turbulence via Weibel instability and the long-term quasi-static annular magnetic field by the streaming electric current account for the measured beam profile. Our work provides direct mapping of laser-driven proton sources in the space-energy domain and reveals the non-laminar beam evolution at featured time scales.

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.

Teaching theatre and drama in primary and secondary schools is a very difficult task worldwide. In China, there is a huge demand for drama teachers who also know practical theatre. Taking on this mission, the Shanghai Theatre Academy started a program of “drama etudes.” This pedagogical experiment stimulated debate about opposing concepts in theatre education: imitation vs. improvisation.

This study aims to locate the knots of cumulative coronavirus disease 2019 (COVID-19) case number during the first-level response to public health emergency in the provinces of China except Hubei. The provinces were grouped into three regions, namely eastern, central and western provinces, and the trends between adjacent knots were compared among the three regions. COVID-19 case number, migration scale index, Baidu index, demographic, economic and public health resource data were collected from 22 Chinese provinces from 19 January 2020 to 12 March 2020. Spline regression was applied to the data of all included, eastern, central and western provinces. The research period was divided into three stages by two knots. The first stage (from 19 January to around 25 January) was similar among three regions. However, in the second stage, growth of COVID-19 case number was flatter and lasted longer in western provinces (from 25 January to 18 February) than in eastern and central provinces (from 26 February to around 11 February). In the third stage, the growth of COVID-19 case number slowed down in all the three regions. Included covariates were different among the three regions. Overall, spline regression with covariates showed the different change patterns in eastern, central and western provinces, which provided a better insight into regional characteristics of COVID-19 pandemic.

Preoperative nutritional status plays an important role in predicting postoperative outcomes. Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) are good tools to assess patients’ nutritional status. They have been used in predicting outcomes in various malignancies, but few studies have focused on pancreatic adenocarcinoma (PDAC) patients. Totally, 306 PDAC patients were enrolled. The propensity score matching (PSM) method was introduced to eliminate the baseline inequivalence. Patients with different PNI (or CONUT) scores showed inequivalence baseline characteristics, and patients with compromised nutritional status were related with a more advanced tumour stage. After PSM, the baseline characteristics were well balanced. Both low PNI (≤45) and high CONUT (≥3) were independent risk factors for poor overall survival (P < 0·05), and the result remained the same after PSM. Survival analysis demonstrated both patients with low PNI and high CONUT score were associated with poorer survival, and the result remained the same after PSM. The results of AUC indicated that CONUT might have a higher sensitivity and specificity in predicting complications and survival. Preoperative low PNI (≤45) and high CONUT (≥3) scores might be reliable predictors of prognosis and surgical complications in PDAC patients. Compared with PNI, CONUT might be more effective.

Androgenetic embryonic stem (AgES) cells offer a possible tool for patient-specific pluripotent stem cells that will benefit genomic imprinting studies and clinic applications. However, the difficulty in producing androgenetic embryos and the unbalanced expression of imprinted genes make the therapeutic applicability of AgES cells uncertain. In this study, we produced androgenetic embryos by injecting two sperm into an enucleated metaphase II (MII) oocyte. By this method, 88.48% of oocytes survived after injection, and 20.24% of these developed to the blastocyst stage. We successfully generated AgES cell lines from the androgenetic embryos and assayed the expression of imprinted genes in the cell lines. We found that the morphological characteristics of AgES cells were similar to that of fertilized embryonic stem cells (fES), such as expression of key pluripotent markers, and generation of cell derivatives representing all three germ layers following in vivo and in vitro differentiation. Furthermore, activation of paternal imprinted genes was detected, H19, ASC12 and Tss3 in AgES cell activation levels were lower while other examined genes showed no significant difference to that of fES cells. Interestingly, among examined maternal imprinted genes, only Mest and Igf2 were significantly increased, while levels of other detected genes were no different to that of fES cells. These results demonstrated that activation of some paternal imprinted genes, as well as recovery of maternal imprinted genes, was present in AgES cells. We differentiated AgES cells into a beating embryoid body in vitro, and discovered that the AgES cells did not show significant higher efficiency in myocardial differentiation potential.

Atomistic simulations of 18 silicon 〈110〉 symmetric tilt grain boundaries are performed using Stillinger Weber, Tersoff, and the optimized Modified Embedded Atom Method potentials. We define a novel structural unit classification through dislocation core analysis to characterize the relaxed GB structures. GBs with the misorientation angle θ ranging from 13.44° to 70.53° are solely composed of Lomer dislocation cores. For GBs with θ less than but close to 70.53°, GB ‘step’ appears and the equilibrated states with lowest GB energies can be attained only when such GB ‘step’ is located in the middle of each single periodic GB structure. For the misorientation angles in the range of 93.37° ≤ θ ≤ 148.41°, GB structures become complicated since they contain multiple types of dislocation cores. This work not only facilitates the structural characterization of silicon 〈110〉 STGBs, but also may provide new insights into mirco-structure design in multicrystalline silicon.

Surface exfoliation was observed on single-crystal silicon surface under the action of compressed plasma flow (CPF). This phenomenon is mainly attributed to the strong transient thermal stress impact induced by CPF. To gain a better understanding of the mechanism, a micro scale model combined with thermal conduction and linear elastic fracture mechanics was built to analyze the thermal stress distribution after energy deposition. After computation with finite element method, J integral parameter was applied as the criterion for fracture initiation evaluation. It was demonstrated that the formation of surface exfoliation calls for specific material, crack depth, and CPF parameter. The results are potentially valuable for plasma/matter interaction understanding and CPF parameter optimization.

The transition metal compound catalysts have been taken a great part in renewable energy conversion and storage systems. Herein, we report the uniform CoFe2O4 nanoparticles with abundant oxygen vacancies and specific active surface exposed through the simple hydrothermal reaction for improving the electrocatalytic performance and stability. They show good electrocatalytic performance for hydrogen evolution reaction in 0.5 M H2SO4 with an onset potential of 20 mV, the overpotential of 45 mV (at j = 10 mA/cm2), and remarkable long-term stability more than 100 h at different current densities and better oxygen reduction reaction activity with lower overpotential in 0.1 M KOH. Moreover, the home-made primary Zn–air batteries, using CoFe2O4 nanoparticles as an air–cathode display the high open-circuit voltage of 1.47 V and the maximum power density of 142 mW/cm2. The two-series-connected batteries fabricated by CoFe2O4 nanoparticles can support a light-emitting diode to work for more than 48 h.

As the strong thermal effect in the surface, intense pulsed ion beam (IPIB) has been extensively used in material surface modification. The ablation is an important part in the interaction process between IPIB and material. In order to investigate the ablation mechanism, combined with IPIB dynamic energy spectrum and infrared imaging diagnostic results, a two-dimensional axisymmetric heat conduction model considering the effect of ablated material was constructed to describe the ablation process and calculate the lost mass of the targets. The influences of beam parameters and ablated matter on the ablation rate were discussed. The experimental and simulative results of ablation threshold and mass were compared.

A 50-yr resolution reconstruction of climate and environment variability during the period 43–14 ka was developed using 26 high-precision U/Th dates and 390 oxygen isotope (δ18O) data of a stalagmite (SJ1) collected from Songjia Cave in central China, which is close to the northwestern boundary of the Asian summer monsoon (ASM). The δ18O record in SJ1 displays significant millennial-scale changes that correlate well in timing and duration with Dansgaard/Oeschger (D/O) events 5–10 and Heinrich event 4 (H4) identified in high-latitude regions of the Northern Hemisphere. Four 230Th dates constrain the H4 event precisely to the period of 39.7 to 38.3 ka. Notable centennial variations of the ASM activity could be observed within the H4 event. The magnitude and duration of D/O event 4.1 recorded in SJ1 are similar to those archived in east China but different from those documented in southwest China, suggesting that the manifestation of this event may be regionally different. The timing, duration and structure of D/O events 5–10 and Heinrich event 4 suggest that temperature changes in both hemispheres have exerted significant influences on the ASM variations in central China.