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Cancers continue to be the second leading cause of death worldwide. Despite the development and improvement of surgery, chemotherapy and radiotherapy in cancer management, effective tumor ablation strategies are still in need due to high cancer patient mortality. Hence, we have established a new approach to achieve treatment-actuated modifications in a tumor microenvironment by using synergistic activity between two potential anticancer drugs. Dual drug delivery of Regorafenib (REGO) and Cisplatin (PT) exhibits a great anticancer potential, as REGO enhances the effect of PT treatment of human cells by providing stability of the microenvironment. However, encapsulation of REGO and PT fanatical by methoxypoly(ethylene glycol)-block-poly(D, L-lactic acid) (PEG-PLA in termed as NPs) is incompetent owing to unsuitability between the binary Free REGO and PT core and the polymeric system. Now, we display that PT can be prepared by hydrophobic coating of the dual drug centers with dioleoylphosphatidic acid (DOPA). The DOPA-covered PT can be co-encapsulated in PLGA NPs alongside REGO to stimulate excellent anticancer property. The occurrence of the PT suggestively enhanced the encapsulations of REGO into PLGA NPs (REGO-PT NPs). Further, the morphology of REGO NPs, PT NPs, and REGO-PT NPs and nanoparticle size was examined by transmission microscopy (TEM), respectively. Furthermore REGO-PT NPs induced significant apoptosis in human lung A549 and ovarian A2780 cancer cells by in vitro. The morphological observation and apoptosis were confirmed by the various biochemical assayes (AO-EB, Nuclear Staining and Annexin V-FITC). In a xenograft model of lung cancer, this nanotherapy shows a durable inhibition of tumor progression upon the administration of a tolerable dose. Our results suggest that a hydrophobic and highly toxic drug can be rationally converted into a pharmacologically efficient and self-deliverable nursing care of nanotherapy. Highlights Dual drug delivery of Regorafenib (REGO) and Cisplatin (PT) exhibits a great anticancer potential, as REGO enhances the effect of PT treatment of human cells by providing stability of the microenvironment. REGO-PT NPs induced significant apoptosis in human lung A549 and ovarian A2780 cancer cells by in vitro. The morphological observation and apoptosis were confirmed by the various biochemical assayes. In a xenograft model of lung cancer, this nanotherapy shows a durable inhibition of tumor progression upon the administration of a tolerable dose.

Aim Many subtropical organisms exhibit an East Asian‐Tethyan disjunction, a distribution split between East Asia and the Mediterranean. The underlying mechanisms and timing have remained unclear to date. The evolutionary history of Quercus section Ilex Loudon, a representative East Asian‐Tethyan disjunct lineage with a rich and widespread fossil record, was investigated to understand the key drivers of this disjunction. Location Eurasia. Methods The phylogeny of Quercus section Ilex was reconstructed using RAD‐seq. Divergence times were estimated based on three fossil calibrations. Ancestral range and niche were reconstructed on the calibrated tree to infer the timing of transitions in geographic distributions and niche. Convergence in ecological space was estimated by fitting alternative multiple‐regime Ornstein‐Uhlenbeck models. Leaf shape affinities among extant and fossil taxa of section Ilex were assessed using geometric morphometric approaches. Results Six clades were well resolved in section Ilex. Ancestral range reconstruction and divergence time dating suggest a wide distribution along the East Tethys seaway, with initial divergence at the mid‐Eocene, and all six clades originating before the Miocene. The section dispersed from East Asia to the Mediterranean at the Eocene‐Oligocene boundary. A shift toward higher elevations was detected in the Himalayan clade during the middle or late Miocene. European fossil lineages during the early Miocene differ in leaf morphology from later lineages, which we infer to be a consequence of adaptive differentiation or species turnover. Main conclusions Quercus section Ilex was widespread along the East Tethys seaway from the middle Eocene onward. The European holly oaks originated from an East Asian ancestral lineage that dispersed to Europe via the Tibet‐Himalaya corridor in the Oligocene. Lowlands along the margins of the Himalayas and through an Oligocene Tibetan valley served as the dispersal route(s) for these species. Changing climates drove Miocene extinction and local adaptation of European lineages.

Gene expression in apple roots in response to various stress conditions is a less-explored research subject. Reliable reference genes for normalizing quantitative gene expression data have not been carefully investigated. In this study, the suitability of a set of 15 apple genes were evaluated for their potential use as reliable reference genes. These genes were selected based on their low variance of gene expression in apple root tissues from a recent RNA-seq data set, and a few previously reported apple reference genes for other tissue types. Four methods, Delta Ct, geNorm, NormFinder and BestKeeper, were used to evaluate their stability in apple root tissues of various genotypes and under different experimental conditions. A small panel of stably expressed genes, MDP0000095375, MDP0000147424, MDP0000233640, MDP0000326399 and MDP0000173025 were recommended for normalizing quantitative gene expression data in apple roots under various abiotic or biotic stresses. When the most stable and least stable reference genes were used for data normalization, significant differences were observed on the expression patterns of two target genes, MdLecRLK5 (MDP0000228426, a gene encoding a lectin receptor like kinase) and MdMAPK3 (MDP0000187103, a gene encoding a mitogen-activated protein kinase). Our data also indicated that for those carefully validated reference genes, a single reference gene is sufficient for reliable normalization of the quantitative gene expression. Depending on the experimental conditions, the most suitable reference genes can be specific to the sample of interest for more reliable RT-qPCR data normalization.

Tibet’s ancient topography and its role in climatic and biotic evolution remain speculative due to a paucity of quantitative surface-height measurements through time and space, and sparse fossil records. However, newly discovered fossils from a present elevation of ∼4,850 m in central Tibet improve substantially our knowledge of the ancient Tibetan environment. The 70 plant fossil taxa so far recovered include the first occurrences of several modern Asian lineages and represent a Middle Eocene (∼47 Mya) humid subtropical ecosystem. The fossils not only record the diverse composition of the ancient Tibetan biota, but also allow us to constrain the Middle Eocene land surface height in central Tibet to ∼1,500 ± 900 m, and quantify the prevailing thermal and hydrological regime. This “Shangri-La”–like ecosystem experienced monsoon seasonality with a mean annual temperature of ∼19 °C, and frosts were rare. It contained few Gondwanan taxa, yet was compositionally similar to contemporaneous floras in both North America and Europe. Our discovery quantifies a key part of Tibetan Paleogene topography and climate, and highlights the importance of Tibet in regard to the origin of modern Asian plant species and the evolution of global biodiversity.

Protocatechuic acid (PCA) is a natural component with multiple biological activities. However, the underlying mechanisms of the effects of PCA on anti-ulcerative colitis (UC) are unclear. A UC mouse model was established by allowing the mice to freely drink a dextran sulfate sodium solution. The mice were administered PCA intragastrically for 7 days. Histological pathology, intestinal flora, and ferroptosis regulators were determined in vivo. Additionally, ferroptotic Caco-2 cells were modeled to investigate the role of PCA in ferroptosis. Our results showed that PCA reduced the levels of the disease activity index, inflammatory factors, and histological damage in UC mice. We also found that the regulation of intestinal flora, especially Bacteroidetes, was one of the potential mechanisms underlying the protective effects of PCA anti-UC. Moreover, PCA downregulated the level of ferroptosis in the colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production compared with the model group. Similar effects of PCA on ferroptosis were observed in Erastin-treated Caco-2 cells. The results obtained using reactive oxygen species assays and the changes in mitochondrial structure observed via scanning electron microscopy also support these results. Our findings suggested that PCA protected against UC by regulating intestinal flora and ferroptosis.

Road traffic sign recognition is an essential function of modern autonomous driving systems. Accurate recognition plays an important role in ensuring vehicle safety and enabling subsequent operations. This paper introduces a Siamese architecture that is combined with feature reconstruction to overcome current method limitations. In detail, the proposed method enhances recognition accuracy by reconstructing convolutional features within a Siamese Neural Network (SNN) framework, integrating an improved Mamba network with mainstream CNN architectures, including VGG-16, AlexNet, ResNet, or MobileNetV2. Through comprehensive architectural comparisons, the optimal network configuration is determined for different application scenarios. Utilizing this approach, the accuracy of traffic sign recognition is substantially improved, addressing the shortcomings of existing technologies. Extensive experimental validation was conducted on multiple datasets. Taking VGG-16 network as an example, the experimental results demonstrated the method’s effectiveness, achieving accuracies of 99.83% on the GTSRB dataset, 99.13% on the TSRD dataset, and 99.07% on the TT100K dataset.

As the ability to collect profiling data in metabolomics increases substantially with the advances in Liquid Chromatography–Mass Spectrometry (LC-MS) instruments, it is urgent to develop new and powerful data analysis approaches to match the big data collected and to extract as much meaningful information as possible from tens of thousands of molecular features. Here, we applied weighted gene co-expression network analysis (WGCNA), an algorithm popularly used in microarray or RNA sequencing, to plasma metabolomic data and demonstrated several advantages of WGCNA over conventional statistical approaches such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). By using WGCNA, a large number of molecular features were clustered into a few modules to reduce the dimension of a dataset, the impact of phenotypic traits such as diet type and genotype on the plasma metabolome was evaluated quantitatively, and hub metabolites were found based on the network graph. Our work revealed that WGCNA is a very powerful tool to decipher, interpret, and visualize metabolomic datasets.

Saline soil is widely distributed in China and poses significant challenges to engineering construction due to its harmful effects, such as salt heaving, dissolution collapse, and frost heaving. The Microbial-Induced Calcite Precipitation (MICP) method is an emerging environmental-friendly modification that can reduce or eliminate the environmental and engineering hazards of saline soil. To verify the feasibility of the MICP method for improving the properties of saline soil, laboratory tests were conducted to study the effects of salt content, activated carbon content and freeze-thaw cycles on the compression and water retention behavior of MICP modified saline soil. The following conclusions were drawn: calcium carbonate produced from the MICP can cement the soil particles of the modified soil structures, which resists the expansion damage caused by salt frost heaving and reduces soil compressibility. Additionally, calcium carbonate particles can fill pores of the soil structures, which improves the water retention capacity of the modified saline soil. The addition of activated carbon can enhance the MICP reaction leading to further reduction in compressibility and enhancement in water retention capacity of MICP modified saline soil.

AIM: Early in their evolution, angiosperms evolved a diversity of leaf form far greater than that of any other group of land plants. Some of this diversity evolved in response to varying climate. Our aim is to test the global relationship between leaf form in woody dicot angiosperms and the climate in which they live. LOCATION: We have compiled a data set describing leaf form (using 31 standardized categorical characters) from 378 natural or naturalized vegetation sites from around the world. Our data include sites from all continents except Antarctica and encompass biomes from tropical to taiga, over a range of elevations from 0.5 m to over 3000 m. METHODS: We chose the Climate Leaf Analysis Multivariate Program sampling, scoring and analytical protocols to test the relationships between climate and leaf form, which is based on canonical correspondence analysis. Cluster analysis evaluates the role of historical factors in shaping the patterns, and pairwise Pearson correlations examine the relationships among leaf characters. RESULTS: Woody dicot leaf characters form a physiognomic spectrum that reflects local climate conditions. On a global scale, correlations between leaf form and climate are consistent, irrespective of climate regime, vegetation type or biogeographic history. Relationships with temperature variables are maintained even when leaf margin characters, regarded as being particularly well correlated with mean annual temperature, are removed. MAIN CONCLUSIONS: In natural woody dicot vegetation an integrated spectrum of leaf form has developed across multiple leaf character states and species. This spectrum appears more strongly influenced by prevailing climate than biogeographic history. The covariation of leaf traits across species suggests strong integration of leaf form. New methods of exploring structure in multidimensional physiognomic space enable better application of leaf form to palaeoclimate reconstruction.

Macrophages in atherosclerotic plaques drive inflammatory responses, degrade lipoproteins, and phagocytose dead cells. MicroRNAs (miRs) control the differentiation and activity of macrophages by regulating the signaling of key transcription factors. However, the functional role of macrophage-related miRs in the immune response during atherogenesis is unknown. Here, we report that miR-155 is specifically expressed in atherosclerotic plaques and proinflammatory macrophages, where it was induced by treatment with mildly oxidized LDL (moxLDL) and IFN-γ. Leukocyte-specific Mir155 deficiency reduced plaque size and number of lesional macrophages after partial carotid ligation in atherosclerotic (Apoe-/-) mice. In macrophages stimulated with moxLDL/IFN-γ in vitro, and in lesional macrophages, loss of Mir155 reduced the expression of the chemokine CCL2, which promotes the recruitment of monocytes to atherosclerotic plaques. Additionally, we found that miR-155 directly repressed expression of BCL6, a transcription factor that attenuates proinflammatory NF-κB signaling. Silencing of Bcl6 in mice harboring Mir155-/- macrophages enhanced plaque formation and CCL2 expression. Taken together, these data demonstrated that miR-155 plays a key role in atherogenic programming of macrophages to sustain and enhance vascular inflammation.