This study was designed to develop and validate models based on delta intratumoral and peritumoral radiomics features from breast masses on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the prediction of axillary lymph node (ALN) pathological complete response (pCR) after neoadjuvant therapy (NAT) in patients with breast cancer (BC). We retrospectively collected data from 187 BC patients with ALN metastases. Radiomics features were extracted from the intratumoral and 3 mm-peritumoral regions on DCE-MRI at baseline and after the 2nd course of NAT to calculate delta intratumoral and peritumoral radiomics features, respectively. After feature selection, the delta intratumoral radiomics (DIR) model and delta peritumoral radiomics (DPR) model were built using the retained features. An ultrasound model was constructed on the basis of preoperative axillary ultrasound results. All variables were screened by univariate and multivariate logistic regression to construct the combined model. The above models were evaluated and compared. In the validation set, the ultrasound model had the lowest AUC, which was lower than those of the DIR, DPR and combined models (0.627 vs 0.825, 0.687, 0.846, respectively). The combined model constructed by delta dual-region radiomics and ultrasound dianogsis was significantly better than the ultrasound model in terms of the Delong test and integrated discrimination improvement (all p < 0.05). Delta intratumoral and peritumoral radiomics based on DCE-MRI have the potential to predict ALN status after NAT. The combined model based on delta dual-region radiomics of breast mass can accurately diagnose ALN-pCR and provide assistance in the selection of axillary surgical approaches for patients.
Adipose-derived mesenchymal stem cells (ADMSCs) used in combination with nanoparticles or scaffolds represent promising candidates for bone engineering. Compared to bone marrow-derived MSCs (BMMSCs), ADMSCs show a relatively low capacity for osteogenesis. In the current study, miR-24 was identified as an osteogenesis- and adipogenesis-related miRNA that performs opposing roles (inhibition in osteogenesis and promotion in adipogenesis) during these two differentiation processes. Through bioinformatics analysis and luciferase reporter assays, homeobox protein Hox-B7 (HOXB7) was identified as a potential novel downstream target of miR-24 that contains a miR-24 binding site in the 3'-UTR of its mRNA. Overexpression of HOXB7 could partly halt the inhibitory effect of miR-24 on osteogenesis, and downregulation of HOXB7 could also partly suppress the positive effect of miR-24 on adipogenesis. Furthermore, immunoprecipitation experiments found that HOXB7 and β-catenin formed a functional complex that acted as an essential modulator during osteogenesis and adipogenesis of ADMSCs. After transfecting ADMSCs with an MSNs-PEI-miR-24 agomir or antagomir and loading the cells onto gelatin-chitosan scaffolds, the compounds were assessed for their abilities to repair the critical-sized calvarial defects in rats. Comprehensive evaluation, including micro-CT, sequential fluorescent labeling, and immunohistochemistry analysis, revealed that silencing miR-24 distinctly promoted in vivo bone remolding, whereas overexpression of miR-24 significantly repressed bone formation. Taken together, our findings demonstrated opposite roles for the miR-24/HOXB7/β-catenin signaling pathway in the osteogenesis and adipogenesis of ADMSCs, which may provide a novel mechanism for determining the balance between these two biological processes.
Mesenchymal stromal cells (MSCs) have shown significant heterogeneity in terms of therapeutic efficacy for inflammatory bowel disease (IBD) treatment, which may be due to an insufficient number of MSCs homing to the damaged tissue of the colon. Engineering MSCs with specific chemokine receptors can enhance the homing ability by lentiviral transduction. However, the unclear specific chemokine profile related to IBD and the safety concerns of viral-based gene delivery limit its application. Thus, a new strategy to modify MSCs to express specific chemokine receptors using mRNA engineering is developed to evaluate the homing ability of MSCs and its therapeutic effects for IBD. We found that CXCL2 and CXCL5 were highly expressed in the inflammatory colon, while MSCs minimally expressed the corresponding receptor CXCR2. Transient expression of CXCR2 in MSC was constructed and exhibited significantly enhanced migration to the inflamed colons, leading to a robust anti-inflammatory effect and high efficacy. Furthermore, the high expression of semaphorins7A on MSCs were found to induce the macrophages to produce IL-10, which may play a critical therapeutic role. This study demonstrated that the specific chemokine receptor CXCR2 mRNA-engineered MSCs not only improves the therapeutic efficacy of IBD but also provides an efficient and safe MSC modification strategy.
Abstract Rice blast, caused by the fungus Magnaporthe oryzae, is one of the most destructive diseases of rice worldwide. The utilization of host resistance (R) genes in rice breeding program is considered as the most economical, effective, environment-friendly strategy for rice blast control. The R gene Pigm, shows high, broad-spectrum and durable resistance to rice blast. Here, we report the successful integration of Pigm into Longke638S (LK638S), an elite thermo-sensitive genic male sterile (TGMS) line in hybrid rice production in China. The integration significantly enhanced the blast resistance of LK638S and the derived hybrid varieties demonstrated exceptional performance in both yield and blast resistance. The improved line Longzhen36S (LZ36S), which recovered 91.84% of the recurrent parent genome. LZ36S exhibited a high blast resistance frequency of 96.4% against 28 blast isolates. Furthermore, the LZ36S-derived hybrids exhibited enhanced resistance to both seedling and panicle blast compared to LK638S-derived hybrids carrying the heterozygous Pi2 gene, all without yield penalty. A total of ninety LK638S derived hybrid varieties have been state or provincial approved and certified with an annual promoting area exceed 964.0 thousand hectares. The LZ36S-derived hybrids can serve as improved versions with enhanced blast resistance, making them viable replacements for LK638S-derived hybrids in commercial production. Moreover, sixteen LZ36S-derived hybrid varieties, all possessing moderate (MR) or high (R) level blast resistance, along with excellent yield and grain quality, have been state or provincial approved and certificated. These LZ36S-derived hybrids show great potential for rapid commercialization, with promoting area of ~ 200 thousand hectares by 2023.
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