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Multisource remote sensing (RS) image classification is a significant research area in Earth observation, aiming to achieve more comprehensive and accurate classification of land cover by integrating data from different sensors. Due to differences in imaging mechanisms and information imbalance between multisource data, multisource RS image classification faces two major challenges as follows. 1) Synergistically capturing features from different modalities to fully exploit complementary information. 2) Adaptively fusing multisource features to overcome the imbalance between modalities and avoid redundant information. This article proposes a spectral–spatial feature extraction network with SSM–CNN (SSFNet) for the collaborative classification of hyperspectral images (HSI) and multispectral images (MSI). Specifically, SSFNet captures long-range spectral correlations in HSI through a bidirectional state–space model (SSM) and learns local correlations between adjacent channels through spectral grouping, achieving global–local spectral information mining in HSI. Simultaneously, joint spatial feature extraction for HSI and MSI data is performed using embedded weight-shared residual feature extractor based on convolutional neural network. This process involves adaptively identifying the importance of features through privatized factors in batch normalization and accurately replacing redundant features. In addition, a spatial attention module is used to further enhance spatial feature representation. Finally, to better accommodate feature distributions and enhance classification outcomes, the extracted spectral–spatial features are combined using weighted fusion, allowing for dynamic integration. Experimental results on two datasets demonstrate that the proposed SSFNet significantly outperforms other competing methods.

Colorectal cancer (CRC) is the third most common cancer worldwide. The role of intestinal microbiota in carcinogenesis has also become an important research topic, and CRC is closely related to the intestinal microbiota. Selenium-containing compounds have attracted more attention as anticancer drugs as they can have minimal side effects. The purpose of this study was to determine and compare the effect of sodium selenite and selenomethionine on the microbial communities of nude mice with CRC. A CRC ectopic tumorigenesis model was established by subcutaneously injecting HCT116 cells into nude mice. The mice were then intraperitoneally injected with sodium selenite and selenomethionine for 24 days to regulate their intestinal microbiota. Compared with sodium selenite, selenomethionine resulted in a greater reduction in the richness and diversity of intestinal microbiota in nude mice with CRC, and the richness and diversity were closer to healthy levels. Selenomethionine also regulated a wider variety of flora. Additionally, sodium selenite and selenomethionine produced different microorganisms, changed function and metabolic pathways in the intestinal microbiota. Both sodium selenite and selenomethionine have certain effects on restoring the intestinal microbial diversity in nude mice with CRC, and the effect of selenomethionine is better than that of sodium selenite.

Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10+ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10+ M2 macrophage production.

Abstracts The COVID-19 pandemic, caused by the SARS-CoV-2 virus and its variants, has posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against SARS-CoV-2 variants. Therefore, novel vaccines to match mutated viral lineages by providing long-term protective immunity are urgently needed. We designed a recombinant adeno-associated virus 5 (rAAV5)-based vaccine (rAAV-COVID-19) by using the SARS-CoV-2 spike protein receptor binding domain (RBD-plus) sequence with both single-stranded (ssAAV5) and self-complementary (scAAV5) delivery vectors and found that it provides excellent protection from SARS-CoV-2 infection. A single-dose vaccination in mice induced a robust immune response; induced neutralizing antibody (NA) titers were maintained at a peak level of over 1:1024 more than a year post-injection and were accompanied by functional T-cell responses. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines produced high levels of serum NAs against the circulating SARS-CoV-2 variants, including Alpha, Beta, Gamma and Delta. A SARS-CoV-2 virus challenge showed that the ssAAV5-RBD-plus vaccine protected both young and old mice from SARS-CoV-2 infection in the upper and lower respiratory tracts. Whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genomes of vaccinated mice one year after vaccination, demonstrating vaccine safety. These results suggest that the rAAV5-based vaccine is safe and effective against SARS-CoV-2 and several variants as it provides long-term protective immunity. This novel vaccine has a significant potential for development into a human prophylactic vaccination to help end the global pandemic.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

Abstract Long non-coding RNA (lncRNA) was reported to be a critical regulator of cellular homeostasis, but poorly understood in idiopathic pulmonary fibrosis (IPF). Here, we systematically identified a crucial lncRNA, p53-induced long non-coding RNA TP53 target 1 (TP53TG1), which was the dysregulated hub gene in IPF regulatory network and one of the top degree genes and down-regulated in IPF-drived fibroblasts. Functional experiments revealed that overexpression of TP53TG1 attenuated the increased expression of fibronectin 1 (Fn1), Collagen 1α1, Collagen 3α1, ACTA2 mRNA, Fn1, and Collagen I protein level, excessive fibroblasts proliferation, migration and differentiation induced by TGF-β1 in MRC-5 as well as PMLFs. In vivo assays identified that forced expression of TP53TG1 by adeno-associated virus 5 (AAV5) not only prevented BLM-induced experimental fibrosis but also reversed established lung fibrosis in the murine model. Mechanistically, TP53TG1 was found to bind to amount of tight junction proteins. Importantly, we found that TP53TG1 binds to the Myosin Heavy Chain 9 (MYH9) to inhibit its protein expression and thus the MYH9-mediated activation of fibroblasts. Collectively, we identified the TP53TG1 as a master suppressor of fibroblast activation and IPF, which could be a potential hub for targeting treatment of the disease.

Gastrointestinal cancer may be associated with dysbiosis, which is characterized by an alteration of the gut microbiota. Understanding the role of gut microbiota in the development of gastrointestinal cancer is useful for cancer prevention and gut microbiota-based therapy. However, the potential role of dysbiosis in the onset of tumorigenesis is not fully understood. While accumulating evidence has demonstrated the presence of dysbiosis in the intestinal microbiota of both healthy individuals and patients with various digestive system diseases, severe dysbiosis is often present in patients with digestive system cancer. Importantly, specific bacteria have been isolated from the fecal samples of these patients. Thus, the association between dysbiosis and the development of digestive system cancer cannot be ignored. A new model describing this relationship must be established. In this review, we postulate that dysbiosis serves as the first hit for the development of digestive system cancer. Dysbiosis-induced alterations, including inflammation, aberrant immune response, bacteria-produced genotoxins, and cellular stress response associated with genetic, epigenetic, and/or neoplastic changes, are second hits that speed carcinogenesis. This review explains the mechanisms for these four pathways and discusses gut microbiota-based therapies. The content included in this review will shed light on gut microbiota-based strategies for cancer prevention and therapy.

Abstract Long non-coding RNAs (lncRNAs) have emerged as critical factors for regulating multiple biological processes during organ fibrosis. However, the mechanism of lncRNAs in idiopathic pulmonary fibrosis (IPF) remains incompletely understood. In the present study, two sets of lncRNAs were defined: IPF pathogenic lncRNAs and IPF progression lncRNAs. IPF pathogenic and progression lncRNAs-mRNAs co-expression networks were constructed to identify essential lncRNAs. Network analysis revealed a key lncRNA CTD-2528L19.6, which was up-regulated in early-stage IPF compared to normal lung tissue, and subsequently down-regulated during advanced-stage IPF. CTD-2528L19.6 was indicated to regulate fibroblast activation in IPF progression by mediating the expression of fibrosis related genes LRRC8C, DDIT4, THBS1, S100A8 and TLR7 et al. Further studies showed that silencing of CTD-2528L19.6 increases the expression of Fn1 and Collagen I both at mRNA and protein levels, promoted the transition of fibroblasts into myofibroblasts and accelerated the migration and proliferation of MRC-5 cells. In contrast, CTD-2528L19.6 overexpression alleviated fibroblast activation in MRC-5 cells induced by TGF-β1. LncRNA CTD-2528L19.6 inhibited fibroblast activation through regulating the expression of LRRC8C in vitro assays. Our results suggest that CTD-2528L19.6 may prevent the progression of IPF from early-stage and alleviate fibroblast activation during the advanced-stage of IPF. Thus, exploring the regulatory effect of lncRNA CTD-2528L19.6 may provide new sights for the prevention and treatment of IPF.

The global incidence of lung cancer is marked by a considerably elevated mortality rate. MicroRNAs (miRNAs) exert pivotal influence in the intricate orchestration of gene regulation, and their dysregulation can precipitate dire consequences, notably cancer. Within this context, miRNAs encapsulated in exosomes manifest a diversified impact on the landscape of lung cancer, wherein their actions may either foster angiogenesis, cell proliferation, and metastasis, or counteract these processes. This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer. Tumor-suppressive miRNAs, such as miR204, miR-192, miR-30a, miR-34a, miR-34b, miR-203, and miR-212, exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness. Conversely, the deleterious effects of tumor-promoting miRNAs like miR-21, miR-106a, miR-155, miR-205, and miR-210 can be attenuated through the application of their respective inhibitors. Distinct miRNAs selectively target various oncogenes, including NUAK Family Kinase 1 (NUAK1), Snail Family Transcriptional Repressor 1 (Snai1), Astrocyte elevated gene-1 (AEG-1), Vimentin, Proliferation and apoptosis adaptor protein 15 (PEA-15/PED), Hypoxia-inducible factor 1-alpha (HIF1), as well as tumor suppressor genes such as phosphatase and tensin homolog (PTEN), Suppressor of cytokine signaling 1 (SOCS1), Tumor protein P53 binding protein 1 (TP53BP1), and PH Domain and Leucine Rich Repeat Protein Phosphatase 2 (PHLP22). This investigative approach proves invaluable in elucidating the specific miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Cancer cells are characterized by aberrant activation of lipid biosynthesis, producing saturated fatty acids and monounsaturated fatty acids via stearoyl-CoA desaturases (SCD) for regulating metabolic and signaling platforms. SCD1 overexpression functions as an oncogene in lung cancer and predicts a poor clinical outcome. This study aimed to investigate the role of SCD1 inhibition by EGFR inhibitor (Gefitinib)-based anti-tumor therapy of lung cancer both in vitro and in vivo. Methods CCK-8 assay was performed to determine cell viability. The SCD1 mRNA level was detected by qPCR. The protein levels were assessed by Western blotting. E-cadherin and N-cadherin levels were determined by immunofluorescence. Apoptosis detection was conducted by flow cytometry. Cell migration or invasion was evaluated by transwell assay. The tumor sizes and tumor volumes were calculated in nude mice by subcutaneous injection of A549 cells transfected with vector of pcDNA3.1-SCD1 or negative control. Expression of Ki-67 was detected by immunohistochemistry. Result SCD1 up-regulated expression was observed in lung cancer cell lines. Cells with overexpressed SCD1 had high IC50 values for Gefitinib in A549 and H1573 cell lines. Overexpression of SCD1 inhibited Gefitinib-induced apoptosis, decreased cell vitality and impaired ability of migration and invasion, while these effects were counteracted by A939572. Mechanistically, SCD1 promoted the activation of proliferation and metastasis-related EGFR/PI3K/AKT signaling, and up-regulated epithelial to mesenchymal transition (EMT) phenotype in the two cell lines, which was restored by SCD1 inhibition. Furthermore, in spite of EGFR inhibition, overexpression of SCD1 in vivo significantly promoted tumor growth by activating EGFR/PI3K/AKT signaling in tumor tissues, but A939572 treatment restricted SCD1-induced tumor progression and inhibited EMT phenotype of cancer cells in vivo. Conclusion These findings indicated that inhibition of oncogene SCD1 is required for targeting EGFR therapy in lung cancer.

A simple and facile one-step method was developed to construct a small molecular prodrug amphiphile self-assembled organic dots CPPG with aggregation-induced emission (AIE) characteristics. Diphenylalanine peptide (FF), which is the essential moiety of the self-assembling peptide-drug conjugate and as its core recognition motifs for molecular self-assembly. In addition, the D-glucose transported protein (GLUT), which is one of the important nutrient transporters and is overexpressed in cancer cells. The conjugation of glycosyl further endues the nanoparticle with good biocompatibility and tumor-targeting ability. Taking advantages of both the cancer cell-targeting capability of small molecular prodrug amphiphile CPPG and the AIE aggregates with strong emission, the prepared CPPG AIE dots can target cancer cells specifically and inhibit the proliferation of cancer cells with good biocompatibility and photostability. Based on the general approach, types of universal organic fluorescent nanoprobes could be facilely constructed for imaging applications and biological therapeutics, which possess the properties of specific recognition and high brightness.

Background: Overexpression of epidermal growth factor receptor (EGFR) has been reported to be implicated in the pathogenesis of non-small cell lung cancer (NSCLC). Several EGFR inhibitors have been used in clinical treatment of NSCLC, but the emergence of EGFRL858R/T790M resistant mutation has reduced the efficacy of the clinical used EGFR inhibitors. There is an urgent need to develop novel EGFRL858R/T790M inhibitors for better NSCLC treatment.Methods: By screening a natural product library, we have identified gossypol as a novel potent inhibitor targeting EGFRL858R/T790M. The activity of gossypol on NSCLC cells was evaluated by cell proliferation, cell apoptosis and cell migration assays. Kinase activity inhibition assay and molecular docking were used to study the inhibition mechanism of gossypol to EGFRL858R/T790M. Western blotting was performed to study the molecular mechanism of gossypol inhibiting the downstream pathways of EGFR.Results: Gossypol inhibited the cell proliferation and cell migration of NSCLC cells, and induced caspase-dependent cell apoptosis of NSCLC cells by upregulating the expression of pro-apoptotic protein BAD. Molecular docking revealed that gossypol could bind to the kinase domain of EGFRL858R/T790M with good binding affinity through hydrogen bonds and hydrophobic interactions. Gossypol inhibited the kinase activity of EGFRL858R/T790M with EC50 of 150.1 nM. Western blotting analysis demonstrated that gossypol inhibited the phosphorylation of EGFR and its downstream signal pathways in a dose-dependent manner.Conclusion: Gossypol inhibited cell proliferation and induced apoptosis of NSCLC cells by targeting EGFRL858R/T790M. Our findings provided a basis for developing novel EGFRL858R/T790M inhibitors for treatment of NSCLC.