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Molecular imprinting technology is widely used for the specific identification of compounds, but the selective recognition mechanisms of the same compounds still need to be further studied. Based on differences in hydrogen bond size and orientation, molecularly imprinted polymers (MIPs) were designed to adsorb flavonols with the same parent core and different hydroxyl groups. A surface-imprinted material was designed with silicon dioxide as the carrier, myricetin as the template molecule, and methacrylic acid (MAA) as the functional monomer. Scanning electron microscopy (SEM), Brunauer–Emmett–Teller surface area (BET) analyses, Fourier-transform infrared spectroscopy (FT-IR), and other characterization experiments were carried out. The intrinsic mechanism of the MIPs was also explored. The MIPs showed good adsorption of myricetin and other flavonoids through hydrogen bonding and steric hindrance. The adsorption capacity was 3.12–9.04 mg/g, and the imprinting factor was 1.78–3.37. Flavonoids with different hydroxyl groups in different numbers and directions had different hydrogen bond strengths with functional monomers. R2, R4, and R1 on 2-phenylchromogenone had stronger electronegativity, and the hydroxyl group was also more likely to form and have stronger hydrogen bonds. The hydroxyl negativity and the degree of steric hindrance of flavonoids played a major role in the recognition of molecularly imprinted materials. This study is of great significance for the synthesis of and selection of templates for analogous molecular imprinting materials.

The integrated development of agricultural land and finance not only promotes rural financial innovation and breaks the bottleneck of agricultural financing but also facilitates agricultural land transfer and scaled operations. This leads to the advancement of the effective growth of contemporary agriculture. The reform of the 'separation of three rights' in agricultural land promotes land circulation, which, in turn, offers an institutional guarantee for the tandem development of rural finance and agricultural land management. This paper measures the comprehensive development index of agricultural land management and rural finance in 30 provinces of China from 2005 to 2020. In light of this, it calculates the degree of coupling and coordination between China's agricultural land management and rural financial development. The Dagum Gini coefficient, kernel density, and the Moran index were used to analyze regional differences and patterns of agglomeration. The study found that the degree of coupling coordination between China's agricultural land management and rural finance is increasing annually. However, there remains a significant gap in achieving high-quality coupling. Notably, the growth rate of rural financial development exceeds that of agricultural land management, and hypervariable density is a major source of regional variation. There is polarization in the coupled development of farmland management and rural finance. Provinces in the eastern and central regions tend to be located in the high–high agglomeration (H–H) in terms of the level of development of agricultural land and financial integration, while the western region tends to fall in low–low aggregation (L–L).

Human mitochondrial chaperonin mHsp60 is essential for mitochondrial function by assisting folding of mitochondrial proteins. Unlike the double-ring bacterial GroEL, mHsp60 exists as a heptameric ring that is unstable and dissociates to subunits. The structural dynamics has been implicated for a unique mechanism of mHsp60. We purified active heptameric mHsp60, and determined a cryo-EM structure of mHsp60 heptamer at 3.4 Å. Of the three domains, the equatorial domains contribute most to the inter-subunit interactions, which include a four-stranded β sheet. Our structural comparison with GroEL shows that mHsp60 contains several unique sequences that directly decrease the sidechain interactions around the β sheet and indirectly shorten β strands by disengaging the backbones of the flanking residues from hydrogen bonding in the β strand conformation. The decreased inter-subunit interactions result in a small inter-subunit interface in mHsp60 compared to GroEL, providing a structural basis for the dynamics of mHsp60 subunit association. Importantly, the unique sequences are conserved among higher eukaryotic mitochondrial chaperonins, suggesting the importance of structural dynamics for eukaryotic chaperonins. Our structural comparison with the single-ring mHsp60-mHsp10 shows that upon mHsp10 binding the shortened inter-subunit β sheet is restored and the overall inter-subunit interface of mHsp60 increases drastically. Our structural basis for the mHsp10 induced stabilization of mHsp60 subunit interaction is consistent with the literature that mHsp10 stabilizes mHsp60 quaternary structure. Together, our studies provide structural bases for structural dynamics of the mHsp60 heptamer and for the stabilizing effect of mHsp10 on mHsp60 subunit association.

Cancer-associated fibroblasts (CAFs) plays an important role in the tumor microenvironment. The heterogeneity of CAFs affects the effect of CAFs on promoting or inhibiting tumors, which can be regulated by other cells in the tumor microenvironment through paracrine methods. The urokinase-type plasminogen activator (PLAU) system mediates cell proliferation, migration, adhesion, and other functions through the proteolytic system, intracellular signal transduction, and chemokine activation. PLAU promotes tumor progression in many tumors. We explored the function of PLAU in ESCC and the influence of PLAU secreted by tumor cells on the heterogeneity of CAFs. We found that PLAU is highly expressed in ESCC, which is related to poor prognosis and can be used as a prognostic marker for ESCC. Through loss-of function and gain-of function experiments, we found that PLAU promoted ESCC proliferation and clone formation via MAPK pathway, and promotes migration by upregulating Slug and MMP9, which can be reversed by the MEK 1/2 inhibitor U0126. At the same time, through sequencing, cytokine detection, and RT-qPCR verification, we found that tumor cells secreted PLAU promoted the conversion of fibroblasts to inflammatory CAFs, which upregulated expression and secretion of IL8 via the uPAR/Akt/NF-κB pathway. The IL8 secreted by CAFs in turn promotes the high expression of PLAU in tumor cells and further promoted the progression of ESCC. In summary, PLAU was not only a prognostic marker of ESCC, which promoted tumor cell proliferation and migration, but also promoted the formation of inflammatory CAFs by the PLAU secreted by tumor cells.

Cancer‐associated fibroblasts (CAF) are a heterogeneous cell population within the tumor microenvironment,and play an important role in tumor development. By regulating the heterogeneity of CAF, transforming growth factor β (TGFβ) influences tumor development. Here, we explored oncogenes regulated by TGFβ1 that are also involved in signaling pathways and interactions within the tumor microenvironment. We analyzed sequencing data of The Cancer Genome Atlas (TCGA) and our own previously established RNA microarray data (GSE53625), as well as esophageal squamous cell carcinoma (ESCC) cell lines with or without TGFβ1 stimulation. We then focused on laminin subunit gamma 1 (LAMC1), which was overexpressed in ESCC cells, affecting patient prognosis, which could be upregulated by TGFβ1 through the synergistic activation of SMAD family member 4 (SMAD4) and SP1. LAMC1 directly promoted the proliferation and migration of tumor cells, mainly via Akt–NFκB–MMP9/14 signaling. Additionally, LAMC1 promoted CXCL1 secretion, which stimulated the formation of inflammatory CAF (iCAF) through CXCR2–pSTAT3. Inflammatory CAF promoted tumor progression. In summary, we identified the dual mechanism by which the upregulation of LAMC1 by TGFβ in tumor cells not only promotes ESCC proliferation and migration, but also indirectly induces carcinogenesis by stimulating CXCL1 secretion to promote the formation of iCAF. This finding suggests that LAMC1 could be a potential therapeutic target and prognostic marker for ESCC. Inflammatory cancer‐associated fibroblasts (iCAF) are known to promote tumor progression. In our study we investigated the role of TGFβ1 on iCAF formation in esophageal squamous cell carcinoma (ESCC). TGFβ1 upregulated LAMC1 expression by activating SMAD4/SP1, which was abrogated by a TGFβR1 inhibitor (SB505124). The proliferation and migration of tumor cells was promoted by LAMC1 via the Akt/NF‐κB/MMP9‐MMP14 pathway. Additionally, LAMC1 facilitated CXCL1 secretion by activating NF‐κB. Tumor‐secreted CXCL1 stimulated the formation of iCAF through CXCR2/pSTAT3, which was blocked by a CXCR2 inhibitor (SB225002). In summary, iCAF promoted ESCC progression by secreting pro‐inflammatory cytokines and chemokines.

Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. However, the underlying molecular mechanism is less clear. Here we report that TDP-43, a RNA-binding protein, underwent positive selection in the mammalian lineage. Furthermore, TDP-43 gene ( Tardbp ) loss induces accumulation of large lipid droplets and severe lipid secretion deficiency in mammary epithelial cells to outside alveolar lumens, eventually resulting in lactation failure and pup starvation within three weeks postpartum. In human milk samples from lactating women, the expression levels of TDP-43 is positively correlated with higher milk output. Mechanistically, TDP-43 exerts post-transcriptional regulation of Btn1a1 and Xdh mRNA stability, which are required for the secretion of lipid droplets from epithelial cells to the lumen. Taken together, our results highlights the critical role of TDP-43 in milk lipid secretion, providing a potential strategy for the screening and intervention of clinical lactation insufficiency. Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. Here the authors found that TDP-43, a RNA-binding protein, is required for milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh mRNA stability.

Cancer vaccines have garnered attention as a potential treatment for cancer metastases. Nevertheless, the clinical response rate to vaccines remains < 30%. Nanoparticles stabilize vaccines and improve antigen recognition and presentation, resulting in high tumor penetration or accumulation, effective co-distribution of drugs to the secondary lymphatic system, and adaptable antigen or adjuvant administration. Such vaccine-like nanomedicines have the ability to eradicate the primary tumors as well as to prevent or eliminate metastases. This review examines state-of-the-art nanocarriers developed to deliver tumor vaccines to metastases, including synthetic, semi-biogenic, and biogenic nanosystems. Moreover, it highlights the physical and pharmacological properties that enhance their anti-metastasis efficiency. This review also addresses the combination of nanovaccines with cancer immunotherapy to target various steps in the metastatic cascade, drawing insights from preclinical and clinical studies. The review concludes with a critical analysis of the challenges and frameworks linked to the clinical translation of cancer nanovaccines.

Quantitative assessment of tree responses to the local environment can help provide scientific guidance for planted forest management. However, research on the climate-growth relationship of Korshinsk peashrub ( Caragana korshinskii Kom.) under different land preparation and post-management (irrigation) conditions is still insufficient. In this study, we collected 223 tree-ring samples from Korshinsk peashrubs using dendroecological methods and systematically quantified the relationships between shrub growth and climatic factors under different management practices in the western Loess Plateau of China. Our findings demonstrated that drought stress caused by scarce precipitation from April to August was the primary factor limiting the growth of Korshinsk peashrubs in the northern and southern mountains of Lanzhou. The “ climwin ” climate model results showed a weak correlation between natural Korshinsk peashrub growth and drought stress, whereas planted Korshinsk peashrub under rain-fed conditions in the southern mountain was significantly ( p <0.05) limited by drought stress from April to August. Moreover, planted Korshinsk peashrub growth under irrigated conditions in the northern mountain was limited only by drought stress in January. Drought model explained 28.9%, 38.3%, and 9.80% of the radial growth variation in Xiguoyuan (XGY), Shuibaozhan (SBZ), and Zhichagou (ZCG) sites, respectively. Artificial supplementary irrigation alleviated the limitation of drought on planted forest growth, which may be implemented for Korshinsk peashrubs planted on sunny slopes, while planted Korshinsk peashrubs under natural rain-fed conditions can be planted on shady slopes through rainwater harvesting and conservation measures such as horizontal ditches and planting holes.

Background The triglyceride-glucose index (TyG) and atherogenic index of plasma (AIP) are emerging metabolic biomarkers associated with cardiovascular diseases. However, their combination prognostic value in patients with critical chronic heart failure (CHF) remains unclear. This study aimed to evaluate the combined predictive effect of these two biomarkers and clarify their interactive patterns in this association. Methods 1,238 patients were recruited via the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, with a median age of 71 years. Multivariable Cox regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve were employed to explore associations between TyG, AIP, and mortality. Mediation analysis was applied to assess their bidirectional mediation effects. Additionally, we developed a machine learning-driven prediction model, which was further utilized to evaluate the two indicators’ incremental predictive value. Results 1,238 patients were included, with 478 (38.61%) dying during follow-up. Fully adjusted Cox regression models revealed that the high TyG and high AIP group was associated with the highest risk of mortality relative to the low TyG and low AIP group (14-day HR 2.18, 95% Cl: 1.44–3.31; 365-day HR 1.92, 95% Cl: 1.38–2.68). ROC analyses demonstrated that the combined TyG-AIP outperformed either marker alone in predicting mortality at all follow-up observation time points (all P  < 0.05). Mediation analysis revealed that TyG mediated the effect of AIP on mortality across all time frames, with a more pronounced effect at 365 days (65.47%) than at 14 days (37.32%). In contrast, AIP served as a mediator in the association between TyG and short-term mortality only (14-day: 30.39%; 30-day: 25.76%). The random forest model confirmed that the incorporation of both the TyG index and AIP remarkably improved predictive capability, corroborating their combined incremental value. Conclusion Combined elevation of TyG and AIP was independently related to an elevated risk of mortality in patients with critical CHF. Combined assessment of these biomarkers may facilitate the early recognition of high-risk subjects and support stage-specific metabolic interventions. Graphical abstract