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The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Background: Aedes albopictus is a major arbovirus vector with small stagnant water containers being its oviposition sites. Mosquitoes search for these sites based on their olfactory cues (odor and moisture emanating from the water at the oviposition site), visual cues (size and color of the site), and gustatory cues (ion and nutrient concentration in that water). The gustatory mechanism through which mosquitoes search for oviposition sites remains unknown. Methods: To investigate the role of taste receptors in Ae. albopictus oviposition site selection, we developed a laboratory model. This model assessed mosquito behavior in locating and detecting oviposition sites, using a location index to quantify site preference and detection time to measure response to water presence. We compared oviposition site-searching efficiency between mosquitoes with blocked and unblocked appendages, targeting the taste organs. Transcriptome sequencing was conducted to identify differentially expressed genes between water-exposed and unexposed mosquitoes. CRISPR/Cas9 technology was then employed to generate a mutant strain with a targeted gene knockout. Results: There was no significant difference between the blocked and unblocked groups in the location index. In contrast, the detection time of the unblocked group differed significantly from all other groups, including those with blocked foreleg tarsus, midleg tarsus, hindleg tarsus, all tibia, and all tarsus. Transcriptome sequencing analyses of water-exposed and unexposed mosquitoes revealed that the taste-related gene gustatory receptor 11(gr11) was differentially expressed. This gene was knocked out with CRISPR/Cas9 technology to generate a pure mutant strain with 2- and 4-bp deletions, which exhibited a significantly longer detection time than the wild-type strain. Conclusions: This study reveals the role of Ae. albopictus gr11 in water detection at oviposition sites, thereby providing a theoretical basis and scientific guidelines for managing the breeding sites of these mosquitoes. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is a non-apoptotic iron-dependent form of cell death implicated in various cancer pathologies. However, its precise role in tumor growth and progression of cervical cancer (CC) remains unclear. Transferrin receptor protein 1 (TFRC), a key molecule associated with ferroptosis, has been identified as influencing a broad range of pathological processes in different cancers. However, the prognostic significance of TFRC in CC remains unclear. The present study utilized bioinformatics to explore the significance of the ferroptosis-related gene TFRC in the progression and prognosis of CC. Methods: We obtained RNA sequencing data and corresponding clinical information on patients with CC from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. Using least absolute shrinkage and selection operator (LASSO) Cox regression, we then generated a multigene signature of five ferroptosis-related genes (FRGs) for the prognostic prediction of CC. We investigated the relationship between TFRC gene expression and immune cell infiltration by employing single-sample GSEA (ssGSEA) analysis. The potential functional role of the TFRC gene was evaluated through gene set enrichment analysis (GSEA). Immunohistochemistry and qPCR was employed to assess TFRC mRNA and protein expression in 33 cases of cervical cancer. Furthermore, the relationship between TFRC mRNA expression and overall survival (OS) was investigated in patients. Results: CC samples had significantly higher TFRC gene expression levels than normal tissue samples. Higher TFRC gene expression levels were strongly associated with higher cancer T stages and OS events. The findings of multivariate analyses illustrated that the OS in CC patients with high TFRC expression is shorter than in patients with low TFRC expression. Significant increases were observed in the levels of TFRC mRNA and protein expression in patients diagnosed with CC. Conclusion: Increased TFRC expression in CC was associated with disease progression, an unfavorable prognosis, and dysregulated immune cell infiltration. In addition, it highlights ferroptosis as a promising therapeutic target for CC. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a serious global health burden because of its high morbidity and mortality rates. Hypoxia and massive lactate production are hallmarks of the CRC microenvironment. However, the effects of hypoxia and lactate metabolism on CRC have not been fully elucidated. This study aimed to develop a novel molecular subtyping based on hypoxia-related genes (HRGs) and lactate metabolism-related genes (LMRGs) and construct a signature to predict the prognosis of patients with CRC and treatment efficacy. Methods: Bulk and single-cell RNA-sequencing and clinical data of CRC were downloaded from the TCGA and GEO databases. HRGs and LMRGs were obtained from the Molecular Signatures Database. The R software package DESeq2 was used to perform differential expression analysis. Molecular subtyping was performed using unsupervised clustering. A predictive signature was developed using univariate Cox regression, random forest model, LASSO, and multivariate Cox regression analyses. Finally, the sensitivity of tumor cells to chemotherapeutic agents before and after hypoxia was verified using in vitro experiments. Results: We classified 575 patients with CRC into three molecular subtypes and were able to distinguish their prognoses clearly. The C1 subtype, which exhibits high levels of hypoxia, has a low proportion of CD8 + T cells and a high proportion of macrophages. The expression of immune checkpoint genes is generally elevated in C1 patients with severe immune dysfunction. Subsequently, we constructed a predictive model, the HLM score, which effectively predicts the prognosis of patients with CRC and the efficacy of immunotherapy. The HLM score was validated in GSE39582, GSE106584, GSE17536, and IMvigor210 datasets. Patients with high HLM scores exhibit high infiltration of CD8 + exhausted T cells (Tex), especially terminal Tex, and oxidative phosphorylation (OXPHOS)−Tex in the immune microenvironment. Finally, in vitro experiments confirmed that CRC cell lines were less sensitive to 5-fluorouracil, oxaliplatin, and irinotecan under hypoxic conditions. Conclusion: We constructed novel hypoxia- and lactate metabolism-related molecular subtypes and revealed their immunological and genetic characteristics. We also developed an HLM scoring system that could be used to predict the prognosis and efficacy of immunotherapy in patients with CRC. [ABSTRACT FROM AUTHOR]

Camellia oleifera Abel. shell (COS) is an agricultural waste in quantities exceeding a million tons annually. The ultrastructure of the COS cell wall and the distribution of lignocellulose components were investigated. The microscopic results showed that COS contains two types of cells, sclerenchyma cells (SC) and parenchyma cells (PC). SC contained 50.4 % hemicellulose, 17.6 % cellulose and 30.9 % lignin while PC contained 35.2 % hemicellulose, 23.7 % cellulose and 35.0 % lignin. The distribution of lignocellulose components in COS is non-homogeneous. Lignin is alternately distributed with polysaccharides in the PC wall. In SC, hemicellulose is mainly present in the secondary wall S2, while lignin was mainly found in the compound middle lamella, and cellulose mainly exists in the secondary wall, S3. A comprehensive model of the cell wall ultrastructure and lignocellulose distribution of COS was given. This study provides a fundamental understanding of COS cell walls and can aid in the future graded utilization of COS. [ABSTRACT FROM AUTHOR]

The structure, composition and mechanical properties of new compatibilizer polypropylene-polyethylene block copolymer (iPP-b-PE) were studied by carbon nuclear magnetic resonance spectroscopy, wide-angle X-ray diffraction (WAXD) in-situ and tensile tests. The effects of iPP-b-PE on the mechanical properties of PP40/UHMWPE blends were investigated using iPP-b-PE compatibilized melt blown polypropylene (PP40) and ultra-high molecular weight polyethylene (UHMWPE). Fixing the mass ratio of PP40 to UHMWPE at 8:2 and other conditions unchanged, the addition of iPP-b-PE increased from 1% to 9%. The results show that the molar ratio of PE to PP in iPP-b-PE is 6:4, and the elongation at break is 2 300%. The addition of iPP-b-PE compatibilizer has little effect on the melt index of the blend, but increases the elongation at break of the blend, and makes the glass transition temperature of PP and UHMWPE close to each other. IPP-b-PE compatibilizer can improve the compatibility between PP and UHMWPE and improve the toughness of the blends. [ABSTRACT FROM AUTHOR]

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine. Realistic tumour models are critical for the development of clinically relevant treatments. Here, the authors develop a lung cancer assembloid model which recapitulates key components of the primary tumour, and can be used to predict clinical outcome. [ABSTRACT FROM AUTHOR]

Purpose: Both of extracellular extravascular volume (EEV) and extracellular volume fraction (ECV) were proposed to quantify enlargement of myocardial interstitial space due to myocardium loss or fibrosis. The study aimed to investigate the feasibility of using EEV derived from myocardial computed tomography (CT) perfusion imaging (VPCT) and extracellular volume quantification with single-energy subtraction CT (ECV− SECT) for quantifying myocardial fibrosis. Methods: In this study, 17 patients with suspected and known coronary artery disease underwent examination using a dual-source CT scanner. The EEV− VPCT was derived from dynamic whole-heart myocardial perfusion imaging, and the ECV_SECT was calculated from late-enhanced images 5 min after bolus contrast injection by subtracting the noncontrast baseline. The late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging was used as a reference. Results: In total, 11 patients and 73 segments exhibited positivity for LGE on CMR imaging. These were classified into three groups according to the segments: fibrotic segments (group I, n = 73), nonfibrotic segments in LGE-positive patients (group II, n = 103), and segments in LGE-negative patients (group III, n = 80). ECV− SECT, EEV− VPCT, myocardial blood flow (MBF), and myocardial blood volume (MBV) significantly differed among these groups (all P < 0.05). ECV− SECT was significantly higher and EEV− VPCT, MBF, and MBV were significantly lower in fibrotic myocardial segments than in nonfibrotic ones (all P < 0.01). ECV− SECT and EEV− VPCT independently affected myocardial fibrosis. There was no significant correlation between ECV− SECT and EEV− VPCT. The capability of EEV− VPCT to diagnose myocardial fibrosis was equivalent to that of ECV− SECT (area under the curve: 0.798 vs. 0.806, P = 0.844). ECV− SECT of > 41.2% and EEV− VPCT of < 10.3% indicated myocardial fibrosis. Conclusions: EEV− VPCT is actually first-pass distribution volume that can feasibly be used to quantify myocardial fibrosis. Furthermore, the diagnostic efficacy of EEV− VPCT is comparable to that of ECV− SECT. [ABSTRACT FROM AUTHOR]