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Surrogate models are commonly used as a substitute for the computation-intensive simulations in design optimization. However, building a high-accuracy surrogate model with limited samples remains a challenging task. In this paper, a novel adaptive-weight ensemble surrogate modeling method is proposed to address this challenge. Instead of using a single error metric, the proposed method takes into account the position of the prediction sample, the mixture error metric and the learning characteristics of the component surrogate models. The effectiveness of proposed ensemble models are tested on five highly nonlinear benchmark functions and a finite element model for the analysis of the frequency response of an automotive exhaust pipe. Comparative results demonstrate the effectiveness and promising potential of proposed method in achieving higher accuracy.

As life expectancy continues to increase, clinicians are challenged by age-related renal impairment that involves podocyte senescence and glomerulosclerosis. There is now compelling evidence that lithium has a potent antiaging activity that ameliorates brain aging and increases longevity in Drosophila and Caenorhabditis elegans. As the major molecular target of lithium action and a multitasking protein kinase recently implicated in a variety of renal diseases, glycogen synthase kinase 3β (GSK3β) is overexpressed and hyperactive with age in glomerular podocytes, correlating with functional and histological signs of kidney aging. Moreover, podocyte-specific ablation of GSK3β substantially attenuated podocyte senescence and glomerular aging in mice. Mechanistically, key mediators of senescence signaling, such as p16INK4A and p53, contain high numbers of GSK3β consensus motifs, physically interact with GSK3β, and act as its putative substrates. In addition, therapeutic targeting of GSK3β by microdose lithium later in life reduced senescence signaling and delayed kidney aging in mice. Furthermore, in psychiatric patients, lithium carbonate therapy inhibited GSK3β activity and mitigated senescence signaling in urinary exfoliated podocytes and was associated with preservation of kidney function. Thus, GSK3β appears to play a key role in podocyte senescence by modulating senescence signaling and may be an actionable senostatic target to delay kidney aging.

Deep learning methods have achieved remarkable success in remote sensing object detection. Existing object detection methods focus on integrating convolutional neural networks (CNNs) and Transformer networks to explore local and global representations to improve performance. However, existing methods relying on fixed convolutional kernels and dense global attention mechanisms suffer from computational redundancy and insufficient discriminative feature extraction, particularly for small and rotation-sensitive targets. To address these limitations, we propose a Dynamic Multi-Kernel Position-Aware Feature Pyramid Network (PAMFPN), which integrates adaptive sparse position modeling and multi-kernel dynamic fusion to achieve robust feature representation. Firstly, we design a position-interactive context module (PICM) that incorporates distance-aware sparse attention and dynamic positional encoding. It selectively focuses computation on sparse targets through a decay function that suppresses background noise while enhancing spatial correlations of critical regions. Secondly, we design a dual-kernel adaptive fusion (DKAF) architecture by combining region-sensitive attention (RSA) and reconfigurable context aggregation (RCA). RSA employs orthogonal large-kernel convolutions to capture anisotropic spatial features for arbitrarily oriented targets, while RCA dynamically adjusts the kernel scales based on content complexity, effectively addressing scale variations and intraclass diversity. Extensive experiments on three benchmark datasets (DOTA-v1.0, SSDD, HWPUVHR-10) demonstrate the effectiveness and versatility of the proposed PAMFPN. This work bridges the gap between efficient computation and robust feature fusion in remote sensing detection, offering a universal solution for real-world applications.

The inter-subspecific indica - japonica hybrid rice confer potential higher yield than the widely used indica - indica intra-subspecific hybrid rice. Nevertheless, the utilization of this strong heterosis is currently hindered by asynchronous diurnal floret opening time (DFOT) of indica and japonica parental lines. Here, we identify OsMYB8 as a key regulator of rice DFOT. OsMYB8 induces the transcription of JA-Ile synthetase OsJAR1 , thereby regulating the expression of genes related to cell osmolality and cell wall remodeling in lodicules to promote floret opening. Natural variations of OsMYB8 promoter contribute to its differential expression, thus differential transcription of OsJAR1 and accumulation of JA-Ile in lodicules of indica and japonica subspecies. Furthermore, introgression of the indica haplotype of OsMYB8 into japonica effectively promotes DFOT in japonica . Our findings reveal an OsMYB8 - OsJAR1 module that regulates differential DFOT in indica and japonica , and provide a strategy for breeding early DFOT japonica to facilitate breeding of indica - japonica hybrids. Florets of indica rice open earlier than japonica rice, hindering utilization of the cross subspecies heterosis. Here, the authors show that an OsMYB8-OsJAR1 module regulates diurnal floret opening time divergences between the two subspecies.

Learner autonomy-the ability to self-direct and regulate learning-is a key determinant of success in online education, yet its quantifiable impact in voluntary noncredit courses remains unclear. Understanding how autonomy translates into measurable behaviors and outcomes in clinical skills training may inform more effective online learning design and learning outcomes. This study aims to quantify the association between behavioral indicators of learner autonomy and performance in a voluntary noncredit online cardiac auscultation course. We conducted a prospective, self‑controlled, single‑center study. A total of 199 registrants (n=122 physicians and n=77 medical students) were recruited via WeChat and attended four weekly 2‑hour synchronous sessions using authentic patient heart sound recordings with imaging‑based explanations. The primary outcome was the final posttraining quiz score (0-100); training effectiveness was assessed by the pre‑ to posttraining score change. The autonomy indicators were full participation (attendance at all four sessions), in‑class engagement (number of responses to brief content‑aligned prompts posed approximately every 10-15 minutes; responses recorded for participation monitoring only), and postclass review (frequency/duration of reviewing recordings and materials). Analyses included Wilcoxon signed rank tests, χ tests, multivariable linear regression, and receiver operating characteristic profiling of \"excellent learners\" (top 10% improvement). Of the 199 registrants, 146 (73.4%) attended ≥1 session and 46 (23.1%) completed all sessions. Median test scores improved from 40 (IQR 20-50) to 70 (IQR 50-83; P<.001). Intrinsic motivation was associated with full participation (χ =4.03; P=.045). In multivariable models, full participation (unstandardized B=41.55, 95% CI 24.43-58.67; standardized β=0.60; P<.001) and in‑class engagement (B=4.79 per additional response, 95% CI 3.05-6.45; β=0.70; P<.001) independently predicted higher final scores (adjusted R =0.48). Receiver operating characteristic profiling indicated that greater postclass review (recordings/materials) led to learners achieving excellent performance. In this voluntary online clinical skills course, showing up consistently, engaging during class, and reviewing after class-practical expressions of learner autonomy-were key correlates of short-term performance. These behaviors may be encouraged through simple, feasible course designs such as clear expectation setting, periodic interactive prompts, and structured review opportunities, which warrant prospective evaluation in future studies.

Speed breeding by artificial control of photothermal conditions facilitates generation advancement but was limited in scale and cost. In this study, we demonstrated a cost-saving off-site summer nursery pattern, taking full advantage of shorter daylength and higher temperature with lower latitude compared to the origin of the soybean cultivars used in the study. This substantially reduced the generation cycles under totally natural conditions. Using this approach, two generations of soybean cultivars from Northeastern Spring Planting Region (NE) and Yellow-Huai-Hai Valleys Summer Planting Region (YHH) were successfully obtained in Beijing and Hainan, respectively, compared to one generation in origin. Fresh-seeding method was also used to further shorten the generation duration by 7–10 days, thereby allowing at least four generations per year. Using DNA markers to define haplotypes of maturity genes E1–E4 , we proposed a model to predict the optimum adaptation region of the advanced generation lines. Taken together, we present a speed-breeding methodology combining off-site nursery, fresh-seeding method, and marker-assisted selection, aimed at accelerating soybean improvement.

Hypoxia-inducible factors (HIFs), as a family of transcription factors involved in the cellular response to hypoxia, are key regulatory factors in the regulation mechanism of an organism’s response to hypoxia. A large number of studies have shown that HIFs are closely related to the angiogenesis, erythropoiesis, cell metabolism, and autophagy of organisms, as well as the occurrence and development of tumours. Therefore, it is of great significance to further study HIFs to understand and treat tumours or other related diseases. This paper summarises the structure, oxygen-dependent degradation mechanism, non-oxygen-dependent degradation mechanism, transcriptional activation mechanism, relevant signalling pathways, and inhibitors of HIFs, in order to provide new clues for the treatment of tumour, vascular, and other related diseases.

S-propargyl-cysteine (SPRC), an excellent endogenous hydrogen sulfide (H 2 S) donor, could elevate H 2 S levels via the cystathionine γ-lyase (CSE)/H 2 S pathway both in vitro and in vivo. However, the immediate release of H 2 S in vivo and daily administration of SPRC potentially limited its clinical use. To solve the fore-mentioned problem, in this study, the dendritic mesoporous silica nanoparticles (DMSN) was firstly prepared, and a sustained H 2 S delivery system consisted of SPRC and DMSN (SPRC@DMSN) was then constructed. Their release profiles, both in vitro and in vivo, were investigated, and their therapeutical effect toward adjuvant-induced arthritis (AIA) rats was also studied. The spherical morphology of DMSN could be observed under scanning Electron Microscope (SEM), and the transmission electron microscope (TEM) images showed a central-radiational pore channel structure of DMSN. DMSN showed excellent SPRC loading capacity and attaining a sustained releasing ability than SPRC both in vitro and in vivo, and the prolonged SPRC releasing could further promote the release of H 2 S in a sustained manner through CSE/H 2 S pathway both in vitro and in vivo. Importantly, the SPRC@DMSN showed promising anti-inflammation effect against AIA in rats was also observed. A sustained H 2 S releasing donor consisting of SPRC and DMSN was constructed in this study, and this sustained H 2 S releasing donor might be of good use for the treatment of AIA.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that mainly erodes joints and surrounding tissues, and if it is not treated in time, it can cause joint deformities and loss of function. S-propargyl-cysteine (SPRC) is an excellent endogenous hydrogen sulfide donor which can relieve the symptoms of RA through the promotion of H2S release via the CSE/H2S pathway in vivo. However, the instant release of H2S in vivo could potentially limit its further clinical use. To solve this problem, in this study, a SPRC-loaded poly(lactic acid) (PLA) microsphere (SPRC@PLA) was prepared, which could release SPRC in vitro in a sustained manner, and further promote sustained in vivo H2S release. Furthermore, its therapeutical effect on RA in rats was also studied. A spherical-like SPRC@PLA was successfully prepared with a diameter of approximately 31.61 μm, yielding rate of 50.66%, loading efficiency of 6.10% and encapsulation efficiency of 52.71%. The SPRC@PLA showed significant prolonged in vitro SPRC release, to 4 days, and additionally, an in vivo H2S release around 3 days could also be observed. In addition, a better therapeutical effect and prolonged administration interval toward RA rats was also observed in the SPRC@PLA group.

Peritoneal dialysis (PD)-associated peritoneal fibrosis is a chronic progress which induces ultrafiltration failure. It remains a challenge to prevent the progression of PD-associated fibrosis in clinic practice. Wnt/β-catenin pathway plays important role in many severe fibrotic diseases, here we investigated its contribution to the development of peritoneal damage. We isolated mesothelial cells (MC) from the effluent of PD patients and found that the expressions of Wnt1, Wnt5a, β-catenin, and LEF1 were increased in patients with more than 1-year PD compared with patients who just started with PD (<1 month). The elevated expressions of Wnts and β-catenin were accompanied with changes in the expressions of E-cadherin, α-SMA, COL-I, and FN mRNA and proteins, which are known related to mesothelial-mesenchymal transition (MMT). In addition, treatment with high glucose significantly increased the expression of Wnt1, Wnt5a, β-catenin, and LEF1 as well as the expression of α-SMA, COL-I, and FN in human peritoneal mesothelial cells (HPMC), whereas the expression of E-cadherin was reduced. Dickkopf-1 (DKK-1) is an endogenous inhibitor of Wnt/β-catenin signaling. Overexpression of DKK1 transgene significantly decreased the expression of β-catenin and attenuated the process of MMT as indicated by the decreased expression of α-SMA, COL-I, and FN and the increased expression of E-cadherin. Furthermore, TGF-β1 treatment significantly activated the Wnt/β-catenin pathway in HPMCs, while DKK1 blocked the TGF-β1-induced Wnt signaling activation and significantly inhibited the process of MMT. These data suggest that the canonical Wnt/β-catenin pathway plays an important role in the MMT and fibrosis induced by PD.