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In the dynamic global trade environment, accurately predicting trade values of diverse commodities is challenged by unpredictable economic and political changes. This study introduces the Meta-TFSTL framework, an innovative neural model that integrates Meta-Learning Enhanced Trade Forecasting with efficient multicommodity STL decomposition to adeptly navigate the complexities of forecasting. Our approach begins with STL decomposition to partition trade value sequences into seasonal, trend, and residual elements, identifying a potential 10-month economic cycle through the Ljung–Box test. The model employs a dual-channel spatiotemporal encoder for processing these components, ensuring a comprehensive grasp of temporal correlations. By constructing spatial and temporal graphs leveraging correlation matrices and graph embeddings and introducing fused attention and multitasking strategies at the decoding phase, Meta-TFSTL surpasses benchmark models in performance. Additionally, integrating meta-learning and fine-tuning techniques enhances shared knowledge across import and export trade predictions. Ultimately, our research significantly advances the precision and efficiency of trade forecasting in a volatile global economic scenario.

The rapid development of tropical island tourism has put forward a higher demand for asphalt pavement construction on the island. However, the asphalt pavement engineering in the offshore area is generally faced with high material transportation costs. Additionally, challenges such as high-temperature climate and heavy-load traffic may lead to permanent pavement deformation. As a typical marine solid waste, shells have high calcium carbonate content and porous structures, which have the potential advantage of modified asphalt. In this study, mixed shell powder was used as a modified material, and 70 # base asphalt and SBS-modified asphalt were mixed, respectively. The effect of asphalt modification was analyzed by basic performance tests and high-temperature rheological tests. An asphalt mixture was prepared by replacing limestone powder with mixed shell powder in equal volume, and its road performance was systematically tested. The modification mechanism was revealed by means of a microscopic test. The results show that the recommended content of mixed shell powder in SBS-modified asphalt is 9%, and 50–100% mixed shell powder can be used to replace mineral filler in base asphalt and single SBS modified asphalt mixture. This study provides effective technical support for the utilization of shell solid waste in offshore areas and the optimization of asphalt pavement performance.

Long non-coding RNAs (lncRNAs) are non-coding RNAs of more than 200 nucleotides. To date, the roles of lncRNAs in soybean fatty acid synthesis have not been fully studied. Here, the low-linolenic acid mutant ‘MT72′ and the wild-type control ‘JN18′ were used as materials. The lncRNAs in young pods at 30 and 40 days (d) after flowering were systematically identified and analyzed using transcriptome sequencing technology combined with bioinformatics tools. A total of 39,324 lncRNAs and 561 differentially expressed lncRNAs were identified. A lncRNAs-miRNAs-protein-coding genes (mRNAs) network was constructed, and 46 lncRNAs, 46 miRNAs and 137 mRNAs were found to be correlated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 12 targeted mRNAs in the competing endogenous RNA network showed that these lncRNAs may be involved in the biological processes of fatty acid transport, lipid synthesis and cell division. Finally, the expression levels of differentially expressed lncRNAs, miRNAs and mRNAs were verified using qRT-PCR. The expression patterns of most genes were consistent with the sequencing results. In conclusion, new information was provided for the study of fatty acid synthesis by lncRNAs in young soybean pods.

Although stapled peptides offer a powerful solution to overcome the susceptibility of linear peptides to proteolytic degradation and improve their ability to cross membranes, an efficient and durable disease treatment strategy has not yet been developed due to the inevitable elimination of peptide inhibitors and rapid accumulation of target proteins. Herein we developed stapled peptide-based proteolysis-targeting chimeras (SP-PROTACs), that simultaneously exhibited improved cellular uptake and proteolytic stability attributed to the stapled peptides, and efficient target protein degradation promoted by the PROTACs. Based on the PMI peptide with dual specificity for both MDM2 and MDMX, a series of SP-PROTACs were designed. Among them, the optimized SPMI-HIF2-1 exhibited similar binding affinity with MDM2 and MDMX but obviously higher helical contents, improved proteolytic stability, better cellular permeability, and a better pharmacokinetic profile compared with its linear counterpart. Importantly, SPMI-HIF2-1 could effectively kill cancer cells and inhibit tumor progression in subcutaneous and orthotopic colorectal cancer xenograft models through simultaneously promoting the atypical degradation of both MDM2 and MDMX and durable p53 activation. An FP-based binding assay and structural modeling analysis of the ternary complex suggested that SPMI-HIF2-1 simultaneously bound with the target protein and E3 ligase. Our findings not only provide a new class of anticancer drug candidates, but also bridge the gap and reduce the physical distance between peptides and PROTACs.

CDK4/6 inhibitors (CDK4/6i) show anticancer activity in certain human malignancies, such as breast cancer. However, their application to other tumor types and intrinsic resistance mechanisms are still unclear. Here, we demonstrate that MYC amplification confers resistance to CDK4/6i in bladder, prostate and breast cancer cells. Mechanistically, MYC binds to the promoter of the E3 ubiquitin ligase KLHL42 and enhances its transcription, leading to RB1 deficiency by inducing both phosphorylated and total pRB1 ubiquitination and degradation. We identify a compound that degrades MYC, A80.2HCl, which induces MYC degradation at nanomolar concentrations, restores pRB1 protein levels and re-establish sensitivity of MYC high-expressing cancer cells to CDK4/6i. The combination of CDK4/6i and A80.2HCl result in marked regression in tumor growth in vivo. Altogether, these results reveal the molecular mechanisms underlying MYC-induced resistance to CDK4/6i and suggest the utilization of the MYC degrading molecule A80.2HCl to potentiate the therapeutic efficacy of CDK4/6i. Several molecular mechanisms, including retinoblastoma protein RB1 deficiency, explain CDK4/6 inhibitors resistance in cancer. Here, the authors show that MYC amplification induces CDK4/6 inhibitors resistance through transcriptional regulation of KLHL42, leading to RB1 degradation and targeting MYC overcomes CDK4/6 resistance in preclinical cancer models.

53BP1 plays an important role in DNA double-strand break (DSB) repair and this activity is negatively regulated by its interaction with Tudor interacting repair regulator (TIRR). However, how the TIRR-53BP1 repair axis is regulated in response to DNA damage remains elusive. Here, we demonstrate that TIRR is translocated to the cytoplasm and degraded upon DNA damage. Ubiquitination of TIRR at lysine 187 by DTX3L is a critical process that regulates NHEJ pathway activity and PARP inhibitor sensitivity by facilitating XPO1-mediated TIRR nuclear export and degradation after DNA damage. We show that DTX3L is overexpressed in prostate cancers in patients and that decreased expression of TIRR due to DTX3L overexpression impairs the negative regulatory effect of TIRR on 53BP1, which consequently induces HR deficiency and chromosomal instability and sensitizes prostate cancer cells to poly (ADP-ribose) polymerase (PARP) inhibitors. Our work reveals a dual action of DTX3L on TIRR degradation and nuclear exportation and identifies DTX3L as an upstream regulator of the TIRR-53BP1 axis that governs DNA repair pathway choice and PARP inhibitor sensitivity. These findings suggest that TIRR ubiquitination and DTX3L overexpression could be viable biomarkers predicting PARP inhibitor sensitivity in cancers. Several molecular mechanisms, including TIRR-53BP1 repair axis, regulate DNA repair pathway choice and PARP inhibitor sensitivity. Here, the authors show that ubiquitination of TIRR by DTX3L is a critical process that regulates NHEJ pathway activity and PARP inhibitor sensitivity by facilitating XPO1-mediated TIRR nuclear export and degradation upon DNA damage.

The identification of mixed monopole and dipole sound sources under highly randomized acoustic environments is of interest in many industrial applications. The DAMAS–MS method is one of the few methods that has been explicitly developed to address this problem. However, it suffers from a critical constraint in that it consistently exhibits limited accuracy in identifying monopole sources, which leads to their underestimation in the final results. To overcome this constraint, this paper proposed a novel identification framework that integrates vision transformer (ViT) with beamforming techniques. The framework leverages preliminary beamforming results to construct input features by extracting the real and imaginary components of the cross-spectral matrix at target frequencies and incorporating spatial position encodings derived from estimated source locations. To ensure adaptability to varying source densities, multiple ViT sub-models are trained on representative scenarios. This strategy enables effective generalization across the target range and supports multi-label identification of monopole and dipole sources with varied configurations. Furthermore, anechoic chamber experiments with synthesized monopole and dipole emitters validate the method’s stability under single-frequency excitation. Compared to the DAMAS–MS method, the proposed method achieves improved identification accuracy for monopole sources, while maintaining comparable performance in dipole source identification, underscoring its potential for practical applications.

Androgen receptor splice variant‐7 (AR‐V7), one of the major driving factors, is the most attractive drug target in castration‐resistant prostate cancer (CRPC). Currently, no available drugs efficiently target AR‐V7 in clinical practice. The DNA binding domain (DBD) is indispensable for the transcriptional activity of AR full length and AR splice variants, including AR‐V7. Based on the homodimerization structure of the AR DBD, a novel peptide‐based proteolysis‐targeting chimera (PROTAC) drug is designed to induce AR and AR‐V7 degradation in a DBD and MDM2‐dependent manner, without showing any activity on other hormone receptors. To overcome the short half‐life and poor cell penetrability of peptide PROTAC drugs, an ultrasmall gold (Au)‐peptide complex platform to deliver the AR DBD PROTAC in vivo is developed. The obtained Au‐AR pep‐PROTAC effectively degrades AR and AR‐V7 in prostate cancer cell lines, particularly in CWR22Rv1 cells with DC50 values 48.8 and 79.2 nM, respectively. Au‐AR pep‐PROTAC results in suppression of AR levels and induces tumor regression in both enzalutamide sensitive and resistant prostate cancer animal models. Further optimization of the Au‐AR pep‐PROTAC can ultimately lead to a new therapy for AR‐V7‐positive CRPC. A novel peptide PROTAC targeting androgen receptor DNA binding domain via AI‐Rosetta assisted design for castration‐resistant prostate cancer therapy is presented.

Developing a reliable system to efficiently and safely deliver peptide drugs into tumor tissues still remains a great challenge since the instability of peptide drugs and low ability to traverse the cell membrane. Herein, we constructed a multifunctional nanoplatform based on porous europium/gadolinium (Eu/Gd)-doped NaLa(MoO 4 ) 2 nanoparticles (NLM NPs) to deliver antitumor peptide of B-cell lymphoma/leukemia-2-like protein 11 (BIM) for cancer therapy. The porous NLM NPs exhibited inherent photoluminescent, magnetic and X-ray absorbable properties, which enable them for triple-modal bioimaging, including fluorescence, magnetic resonance imaging (MRI) and computed tomography (CT). This triple-modal bioimaging can contribute to monitoring NLM NPs biodistribution and guiding therapy in vitro and in vivo . Furthermore, the NLM NPs showed negligible cytotoxicity in vitro and tissue toxicity in vivo . Importantly, NLM NPs could load the antitumor peptide of BIM and efficiently improve the resistance of peptide drugs to proteolysis. The BIM peptide was efficiently delivered into the tumor cells by NLM NPs, which can inhibit the growth and promote the apoptosis of cancer cells in vitro , significantly inhibit the tumor growth in vivo . Notably, NLM-BIM theranostic nanoplatform exhibits low systemic toxicity and fewer side effects in vivo . The NLM NPs can serve as a promising multifunctional peptide delivery nanoplatform for multi-modal bioimaging and cancer therapy.

As the world's first oral nuclear export inhibitor, selinexor is increasingly being used in clinical applications for malignant tumors. However, there is no extensive exploration on selinexor's adverse events (ADEs), necessitating a real-word assessment of its clinical medication safety. FAERS data (July 2019–June 2023) were searched for selinexor ADE reports across all indications. Use the system organ class (SOC) and preferred terms (PT) from the medical dictionary for regulatory activities (MedDRA) to describe, categorize, and statistic ADEs. Disproportionality analysis was employed through calculation of reporting odds ratio (ROR) and proportional reporting ratio (PRR). Based on total of 4392 selinexor related ADE reports as the primary suspect (PS), of which 2595 instances were severe outcomes. The predominant ADEs included gastrointestinal disorders, myelosuppression symptoms, and various nonspecific manifestations. 124 signals associated with selinexor ADE were detected, and 10 of these top 15 signals were not included into the instructions. Our study provides real-world evidence regarding the drug safety of selinexor, which is crucial for clinicians to safeguard patients’ health.