Objectives/Goals: Endometrial cancer (ECa) incidence is rising rapidly in women under 40 years of age, and response rates and progression-free survival remain poor in advanced ECa. New targeted therapies are urgently needed. The objective of this study is to develop and test a potent inhibitor that targets midkine (MDK) for treating ECa. Methods/Study Population: Using the three-dimensional structure of human MDK, we rationally designed a small organic molecule (HBS-101) that directly binds with MDK and that functions as a MDK inhibitor. Microscale thermophoresis assay (MST) and in silico docking studies were used to demonstrate direct binding of HBS-101 to MDK. In vitro activity was tested using MTT, clonogenicity, and apoptosis assays. Mechanistic studies were conducted using Western blot, RT-qPCR, STAT3 and NFkB reporter gene assays, RNseq, and TEM. Status of MDK in ECa was determined using TNMplot database. Pharmacokinetics, Maximum Tolerable Dose, and in vivo efficacy studies were conducted using mouse models. HBS-101 efficacy in chemotherapy-resistant ECa was demonstrated using therapy-resistant primary ECa (TR-ECa) cells generated in-house. Results/Anticipated Results: MDK is highly expressed in ECa tumors compared to normal tissues. MDK and its receptors are expressed in established and primary ECa cell lines. Knockdown of MDK reduced ECa cell proliferation and colony formation. HBS-101 directly binds to MDK with nanomolar affinity, and a potential interaction surface on MDK was identified. HBS-101 decreased ECa cell viability and colony formation with an IC₅₀ ranging from 0.5 to 5 µM. Mechanistic studies showed that HBS-101 suppressed STAT3 and NFκB activity and induced cell death, ER stress, and ferroptosis. TR-ECa cells exhibited sensitivity to HBS-101. HBS-101 possesses favorable drug-like properties, including oral bioavailability, in vivo stability and little in vivo toxicity up to 10 mg/kg. HBS-101 significantly inhibited tumor growth in ECa PDX models. Discussion/Significance of Impact: HBS-101 is a novel therapeutic agent that targets MDK via a unique mechanism, shows favorable pharmacokinetics, and induces apoptosis and ferroptosis in ECa cells by blocking MDK signaling. HBS-101 shows promise in treating high-grade and therapy-resistant ECa and may help overcome the current lack of good treatment options for these patients.

We investigate the onset of transient natural convection in fluid layers subject to volumetric radiative heating and surface cooling. Linear stability analysis reveals a non-monotonic evolution of stability in deep layers, where the flow undergoes successive stages of initial destabilisation, intermediate suppression and eventual restabilisation. This complex temporal behaviour necessitates the definition of dual critical Rayleigh numbers: a lower bound marking the onset of initial instability and an upper bound required for sustained convection. To efficiently predict these thresholds, we develop a local Rayleigh number model that depends solely on the instantaneous conductive temperature profile. When the Rayleigh number exceeds the lower bound, the critical time $t_c$ for flow onset is determined through transient linear stability analysis, and scaling laws are derived to characterise the dependence of $t_c$ on the Rayleigh number $\textit{Ra}$, Prandtl number $\textit{Pr}$, cooling parameter $\phi$ and layer depth $H$. Two distinct instability triggering mechanisms are identified: a top-triggered regime, where $t_c \sim [\textit{Ra} \textit{Pr} \phi /(2+\textit{Pr})]^{-1/2}$, and a bottom-triggered regime, where $t_c \sim [\textit{Ra} \textit{Pr} \exp (-H)/(2+\textit{Pr})]^{-1/2}$. All theoretical predictions are rigorously validated against direct numerical simulations, providing a unified predictive framework for convective onset in systems governed by coupled effects of radiation absorption and surface cooling.

This study tested the effects of soil amendment with orange peel powder (Citrus sinensis L.) on Brassica rapa growth, the performance of the aphid Myzus persicae Sulzer, and the foraging behaviour of its parasitoid Aphidius gifuensis Ashmead. Three peel: soil ratios (1:10, 1:15, 1:20 w/w) were compared with an unamended control. The 1:10 amendment significantly reduced seed germination, plant height, leaf size, and fresh weight, while the 1:20 amendment also decreased fresh weight. Aphid nymphal development was significantly delayed in the 1:10 and 1:15 treatments, and adult weight gain was reduced in the 1:15 treatment. Aphid population growth and parasitoid foraging time were unaffected across treatments. The results indicate that orange peel amendments can delay aphid development but also suppress plant growth at higher concentrations, highlighting the need for optimized application rates. This study supports further exploration of orange peel as a sustainable soil amendment in integrated pest management.

Appropriate soil water and nitrogen (N) management strategies are critical for achieving sustainable agricultural development in drylands. Straw mulching has been used to improve crop yield and water use efficiency (WUE), but N management strategies may need to be adjusted from conventional practice. The current study investigated the interactive effects of N application rate (conventional and high N rate), N application frequencies (single, and split N in 2 – 3 applications) and seasonal conditions on wheat population density dynamics, yield, harvest index (HI), grain protein content, water- and N-use efficiency, and residual soil N under straw mulching on the Loess Plateau of China. Nitrogen rate had no effect on yield, HI, WUE and grain protein content, but high N rate resulted in lower grain weight and nitrogen partial factor productivity (PFPN), and higher soil N residue. Splitting N applications significantly improved grain yield (7%), HI (9%), grain protein content (5%), PFPN and N harvest index, along with a reduction in soil N residue, compared to single application. However, there was no difference in above traits between split-N in 2 and 3 applications. Conventional N rate (vs. high N rate) and split N application (vs. single application) both alleviated the negative correlation between grain yield and grain protein content, and split N application increased grain N removal per unit yield compared to single N application. It is concluded that conventional N rate combined with split application in two doses, is suitable for straw mulching in drylands of the Loess Plateau, China.

In the fields of meal-assisting robotics and human–robot interaction (HRI), real-time and accurate mouth pose estimation is critical for ensuring interaction safety and improving user experience. The complexity arises from the diverse opening degrees of mouths, variations in orientation, and external factors such as lighting conditions and occlusions, which pose significant challenges for real-time and accurate posture estimation of mouths. In response to the above-mentioned issues, this paper proposes a novel method for point cloud fitting and posture estimation of mouth opening degrees (FP-MODs). The proposed method leverages both RGB and depth images captured from a single viewpoint, integrating geometric modeling with advanced point cloud processing techniques to achieve robust and accurate mouth posture estimation. The innovation of this work lies in the hypothesis that different states of mouth openings can be effectively described by distinct geometric shapes: closed mouths are modeled by spatial quadratic surfaces, half-open mouths by spatial ellipses, and fully open mouths by spatial circles. Then, based on these hypotheses, we developed algorithms for fitting geometric models to point clouds obtained from mouth regions, respectively. Specifically, for the closed mouth state, we employ an algorithm based on least squares optimization to fit a spatial quadratic surface to the point cloud data. For the half-open or fully open mouth states, we combine inverse projection methods with least squares fitting to model the contour as a spatial ellipse and circle, respectively. Finally, to evaluate the effectiveness of the proposed FP-MODs method, extensive actual experiments were conducted under varying conditions, including different orientations and various types of mouths. The results demonstrate that the proposed FP-MODs method achieves high accuracy and robustness. This study can provide a theoretical foundation and technical support for improving HRI and food delivery safety in the field of robotics.

Spodoptera frugiperda (Lepidoptera: Noctuidae), commonly known as the fall armyworm (FAW), is an invasive pest known for its rapid migration, strong adaptability, and wide host range. Small heat shock proteins (sHsps) are a specific class of Hsps associated with the molecular mechanisms of insect growth and development and the response to abiotic stresses, such as extreme temperatures, ultraviolet (UV) rays, and pesticides. Herein, six sHsps, SfsHsp11.2, SfsHsp15.8, SfsHsp20.2, SfsHsp21.4, SfsHsp22, and SfsHsp26.6, were successfully cloned and identified from FAW. The six SfsHsps all have an α-crystallin domain in their amino acid sequences. Furthermore, we investigated the expression patterns of these six SfsHsps in different tissues and developmental stages of FAW using real-time quantitative polymerase chain reaction. Their expression levels in adult FAW were also analysed under extreme temperatures (36°C and 4°C) and UV-A stress for different durations (0, 30, 60, 90, and 120 min). Our findings revealed distinct expression profiles for the six SfsHsps in different FAW tissues and developmental stages. Notably, under temperature and UV-A stress, most SfsHsp genes were significantly upregulated in adults. Our findings strongly indicate that SfsHsps are crucial in the development and stress response of S. frugiperda.

Emission line galaxies (ELGs) are crucial for cosmological studies, particularly in understanding the large-scale structure of the Universe and the role of dark energy. ELGs form an essential component of the target catalogue for the Dark Energy Spectroscopic Instrument (DESI), a major astronomical survey. However, the accurate selection of ELGs for such surveys is challenging due to the inherent uncertainties in determining their redshifts with photometric data. In order to improve the accuracy of photometric redshift estimation for ELGs, we propose a novel approach CNN–MLP that combines convolutional neural networks (CNNs) with multilayer perceptrons (MLPs). This approach integrates both images and photometric data derived from the DESI Legacy Imaging Surveys Data Release 10. By leveraging the complementary strengths of CNNs (for image data processing) and MLPs (for photometric feature integration), the CNN–MLP model achieves a $\sigma_{\mathrm{NMAD}}$ (normalised median absolute deviation) of 0.0140 and an outlier fraction of 2.57%. Compared to other models, CNN–MLP demonstrates a significant improvement in the accuracy of ELG photometric redshift estimation, which directly benefits the target selection process for DESI. In addition, we explore the photometric redshifts of different galaxy types (Starforming, Starburst, AGN, and Broadline). Furthermore, this approach will contribute to more reliable photometric redshift estimation in ongoing and future large-scale sky surveys (e.g. LSST, CSST, and Euclid), enhancing the overall efficiency of cosmological research and galaxy surveys.

This paper investigates the long-run nexus between wealth inequality and aggregate output using a DSGE model in which wealth inequality endogenously affects individual entrepreneurship incentives, thereby influencing aggregate output. Our model passes the indirect inference test against the UK data from 1870 to 2015. We find that shocks to aggregate TFP, entrepreneurial barriers, government grant support and general government spending played significant roles in shaping historical inequality dynamics in the UK. Directly removing entrepreneurial barriers or indirectly providing government grant support to the private sector such as through inclusive loan subsidies are effective means of reducing inequality and stimulating output growth.

Laser-driven inertial confinement fusion (ICF) diagnostics play a crucial role in understanding the complex physical processes governing ICF and enabling ignition. During the ICF process, the interaction between the high-power laser and ablation material leads to the formation of a plasma critical surface, which reflects a significant portion of the driving laser, reducing the efficiency of laser energy conversion into implosive kinetic energy. Effective diagnostic methods for the critical surface remain elusive. In this work, we propose a novel optical diagnostic approach to investigate the plasma critical surface. This method has been experimentally validated, providing new insights into the critical surface morphology and dynamics. This advancement represents a significant step forward in ICF diagnostic capabilities, with the potential to inform strategies for enhancing the uniformity of the driving laser and target surface, ultimately improving the efficiency of converting laser energy into implosion kinetic energy and enabling ignition.

Echinochloa crus-galli var. crus-galli (L.) P. Beauv. (EC), Echinochloa crus-galli var. mitis (Pursh) Petermann (ECM), and Echinochloa glabrescens Munro ex Hook. f. (EG) are all serious rice (Oryza sativa L.) weeds that are usually treated as a single species in weed management practices. To determine interspecific and intraspecific differences in seed germination responding to different temperatures among the three Echinochloa weeds, we conducted field surveys and collected 66 EC, 141 ECM, and 120 EG populations from rice fields of East China in 2022; and tested their seed germination under 28/15 C (day/night), 30/20 C, and 35/25 C regimes, simulating temperatures of rice-planting periods for double-cropping early rice, single-cropping rice, and double-cropping late rice, respectively. In EC, ECM, and EG, seed percentage germination (cumulative percentage of germinated seed) and germination index (sum of the ratio of germinated seeds to the corresponding days) increased with increasing temperatures. At 28/15 C, the average percentage germination of EC populations (67.5%) was significantly (P < 0.05) higher compared with ECM (46.4%) and EG (43.7%); GD50 (duration for 50% total germination) for EC populations (5.2 d) was significantly shorter compared with ECM (5.9 d) and EG (5.8 d). At 35/25 C, the percentage germinations of EC (90.7%), ECM (80.5%), and EG (80.3%) were all significantly the highest among the three temperature treatments, respectively, and the GD50 values for EC (2.5 d), ECM (2.6 d), and EG (2.7 d) were all significantly the lowest. At 30/20 C and 35/25 C, the average germination percentages of populations collected from transplanted rice fields were significantly higher than those of populations collected from direct-seeded rice fields. Moreover, among EG populations, the longitudes and latitudes of collection locations were significantly correlated with seed percentage germination and germination indices. According to the interspecific differences and intraspecific variations of Echinochloa species, weed management strategies should also be customized according to the species and population characteristics in seed germination.

A high-energy pulsed vacuum ultraviolet (VUV) solid-state laser at 177 nm with high peak power by the sixth harmonic of a neodymium-doped yttrium aluminum garnet (Nd:YAG) amplifier in a KBe2BO3F2 prism-coupled device was demonstrated. The ultraviolet (UV) pump laser is a 352 ps pulsed, spatial top-hat super-Gaussian beam at 355 nm. A high energy of a 7.12 mJ VUV laser at 177 nm is obtained with a pulse width of 255 ps, indicating a peak power of 28 MW, and the conversion efficiency is 9.42% from 355 to 177 nm. The measured results fitted well with the theoretical prediction. It is the highest pulse energy and highest peak power ever reported in the VUV range for any solid-state lasers. The high-energy, high-peak-power, and high-spatial-uniformity VUV laser is of great interest for ultra-fine machining and particle-size measurements using UV in-line Fraunhofer holography diagnostics.

Femtosecond oscillators with gigahertz (GHz) repetition rate are appealing sources for spectroscopic applications benefiting from the individually accessible and high-power comb line. The mode mismatch between the potent pump laser diode (LD) and the incredibly small laser cavity, however, limits the average output power of existing GHz Kerr-lens mode-locked (KLM) oscillators to tens of milliwatts. Here, we present a novel method that solves the difficulty and permits high average power LD-pumped KLM oscillators at GHz repetition rate. We propose a numerical simulation method to guide the realization of Kerr-lens mode-locking and comprehend the dynamics of the Kerr-lens mode-locking process. As a proof-of-principle demonstration, an LD-pumped Yb:KGW oscillator with up to 6.17-W average power and 184-fs pulse duration at 1.6-GHz repetition rate is conducted. The simulation had a good agreement with the experimental results. The cost-effective, compact and powerful laser source opens up new possibilities for research and industrial applications.

Dietary n-3 PUFA may have potential benefits in preventing peptic ulcer disease (PUD). However, data from observational epidemiological studies are limited. Thus, we conducted a Mendelian randomisation analysis to reveal the causal impact of n-3 PUFA on PUD. Genetic variants strongly associated with plasma levels of total or individual n-3 PUFA including plant-derived α-linolenic acid and marine-derived EPA, DPA and DHA were enrolled as instrumental variables. Effect size estimates of the n-3 PUFA-associated genetic variants with PUD were evaluated using data from the UK biobank. Per one sd increase in the level of total n-3 PUFA in plasma was significantly associated with a lower risk of PUD (OR = 0·91; 95 % CI 0·85, 0·99; P = 0·020). The OR were 0·81 (95 % CI 0·67, 0·97) for EPA, 0·72 (95 % CI 0·58, 0·91) for DPA and 0·87 (95 % CI 0·80, 0·94) for DHA. Genetically predicted α-linolenic acid levels in plasma had no significant association with the risk of PUD (OR = 5·41; 95 % CI 0·70, 41·7). Genetically predicted plasma levels of n-3 PUFA were inversely associated with the risk of PUD, especially marine-based n-3 PUFA. Such findings may have offered an effective and feasible strategy for the primary prevention of PUD.

This study examines the pursuit-evasion game involving unmanned aerial vehicles (UAVs), with a specific focus on the scenario of N-pursuers-one-escapee. The primary objective is to develop an optimal strategy for the escapee when the pursuers possess superior capabilities. To obtain this objective, we conduct the following study. Firstly, to enhance realism, a non-cooperative differential game model is formulated, incorporating multiple motion characteristics, including aerodynamics, overloading, and imposed constraints. Secondly, the end-value performance index is subsequently converted to an integral one, simplifying the solution process of the Hamilton-Jacobi-Bellman (HJB) equation. An iterative method is utilised to determine the covariates using the Cauchy initial value problem, and its convergence and uniqueness are established. The optimal avoidance strategy is subsequently derived from the covariates. Finally, the superiority of the proposed strategy is validated through simulation experiments and compared to three advanced optimal avoidance strategies. A total of 1,000 anti-jamming simulation experiments are conducted to verify the robustness of the proposed strategy.

The absorption and distribution of radiocarbon-labeled urea at the ultratrace level were investigated with a 14C-AMS biotracer method. The radiopharmaceutical concentrations in the plasma, heart, liver, spleen, lung, kidney, stomach, brain, bladder, muscle, testis, and fat of rats after oral administration of 14C urea at ultratrace doses were determined by AMS, and the concentration-time curves in plasma and tissues and pharmacokinetic distribution data were obtained. This study provides an analytical method for the pharmacokinetic parameters and tissue distribution of exogenous urea in rats at ultratrace doses and explores the feasibility of evaluation and long-term tracking of ultratrace doses of drugs with AMS.

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.