Intratumoral and peritumoral radiomics model based on abdominal ultrasound for predicting Ki-67 expression in patients with hepatocellular cancer.

Background: Hepatocellular cancer (HCC) is one of the most common tumors worldwide, and Ki-67 is highly important in the assessment of HCC. Our study aimed to evaluate the value of ultrasound radiomics based on intratumoral and peritumoral tissues in predicting Ki-67 expression levels in patients with HCC. Methods: We conducted a retrospective analysis of ultrasonic and clinical data from 118 patients diagnosed with HCC through histopathological examination of surgical specimens in our hospital between September 2019 and January 2023. Radiomics features were extracted from ultrasound images of both intratumoral and peritumoral regions. To select the optimal features, we utilized the t-test and the least absolute shrinkage and selection operator (LASSO). We compared the area under the curve (AUC) values to determine the most effective modeling method. Subsequently, we developed four models: the intratumoral model, the peritumoral model, combined model #1, and combined model #2. Results: Of the 118 patients, 64 were confirmed to have high Ki-67 expression while 54 were confirmed to have low Ki-67 expression. The AUC of the intratumoral model was 0.796 (0.649-0.942), and the AUC of the peritumoral model was 0.772 (0.619-0.926). Furthermore, combined model#1 yielded an AUC of 0.870 (0.751-0.989), and the AUC of combined model#2 was 0.762 (0.605-0.918). Among these models, combined model#1 showed the best performance in terms of AUC, accuracy, F1-score, and decision curve analysis (DCA). Conclusion: We presented an ultrasound radiomics model that utilizes both intratumoral and peritumoral tissue information to accurately predict Ki-67 expression in HCC patients. We believe that incorporating both regions in a proper manner can enhance the diagnostic performance of the prediction model. Nevertheless, it is not sufficient to include both regions in the region of interest (ROI) without careful consideration.

Magnetic detection under high pressures using designed silicon vacancy centres in silicon carbide.

Pressure-induced magnetic phase transitions are attracting interest as a means to detect superconducting behaviour at high pressures in diamond anvil cells, but determining the local magnetic properties of samples is a challenge due to the small volumes of sample chambers. Optically detected magnetic resonance of nitrogen vacancy centres in diamond has recently been used for the in situ detection of pressure-induced phase transitions. However, owing to their four orientation axes and temperature-dependent zero-field splitting, interpreting these optically detected magnetic resonance spectra remains challenging. Here we study the optical and spin properties of implanted silicon vacancy defects in 4H-silicon carbide that exhibit single-axis and temperature-independent zero-field splitting. Using this technique, we observe the magnetic phase transition of Nd2Fe14B at about 7 GPa and map the critical temperature-pressure phase diagram of the superconductor YBa2Cu3O6.6. These results highlight the potential of silicon vacancy-based quantum sensors for in situ magnetic detection at high pressures.

Orbital-Hybridization-Driven Charge Density Wave Transition in CsV3 Sb5 Kagome Superconductor.

Owing to its inherent non-trivial geometry, the unique structural motif of the recently discovered kagome topological superconductor AV3 Sb5 (A = K, Rb, Cs) is an ideal host of diverse topologically non-trivial phenomena, including giant anomalous Hall conductivity, topological charge order, charge density wave (CDW), and unconventional superconductivity. Despite possessing a normal-state CDW order in the form of topological chiral charge order and diverse superconducting gaps structures, it remains unclear how fundamental atomic-level properties and many-body effects including Fermi surface nesting, electron-phonon coupling, and orbital hybridization contribute to these symmetry-breaking phenomena. Here, the direct participation of the V3d-Sb5p orbital hybridization in mediating the CDW phase transition in CsV3 Sb5 is reported. The combination of temperature-dependent X-ray absorption and first-principles studies clearly indicates the inverse Star-of-David structure as the preferred reconstruction in the low-temperature CDW phase. The results highlight the critical role that Sb orbitals play and establish orbital hybridization as the direct mediator of the CDW states and structural transition dynamics in kagome unconventional superconductors. This is a significant step toward the fundamental understanding and control of the emerging correlated phases from the kagome lattice through the orbital interactions and provides promising approaches to novel regimes in unconventional orders and topology.

Targeting BMI-1-mediated epithelial-mesenchymal transition to inhibit colorectal cancer liver metastasis.

Liver is the most common metastatic site for colorectal cancer (CRC), there is no satisfied approach to treat CRC liver metastasis (CRCLM). Here, we investigated the role of a polycomb protein BMI-1 in CRCLM. Immunohistochemical analysis showed that BMI-1 expression in liver metastases was upregulated and associated with T4 stage, invasion depth and right-sided primary tumor. Knockdown BMI-1 in high metastatic HCT116 and LOVO cells repressed the migratory/invasive phenotype and reversed epithelial-mesenchymal transition (EMT), while BMI-1 overexpression in low metastatic Ls174T and DLD1 cells enhanced invasiveness and EMT. The effects of BMI-1 in CRC cells were related to upregulating snail via AKT/GSK-3ß pathway. Furthermore, knockdown BMI-1 in HCT116 and LOVO cells reduced CRCLM using experimental liver metastasis mice model. Meanwhile, BMI-1 overexpression in Ls174T and DLD1 significantly increased CRCLM. Moreover, sodium butyrate, a histone deacetylase and BMI-1 inhibitor, reduced HCT116 and LOVO liver metastasis in immunodeficient mice. Our results suggest that BMI-1 is a major regulator of CRCLM and provide a potent molecular target for CRCLM treatment.

MicroRNA-30b-5p functions as a metastasis suppressor in colorectal cancer by targeting Rap1b.

Colorectal liver metastasis (CRLM) is the leading cause of death in patients with colorectal cancer (CRC). MiR-30b-5p can function as an oncogene or tumor suppressor in cancers, but its role in CRLM is still unknown. Here, we found that miR-30b-5p overexpression suppressed the invasion, migration, adhesion, and motility of HCT116 and LoVo cells. The expression of EMT (Zeb1, Snail, and vimentin) and adhesion-related proteins (p-paxillin and p-Src) was decreased. We validated Rap1b, a Ras family small GTPase that regulates cell adhesion and mobility, as the direct and functional target of miR-30b-5p. Rap1b overexpression rescued the aggressive characteristics of CRC cells that were inhibited by miR-30b-5p. Rap1b knockdown suppressed invasion and migration and decreased CRC cell-matrix adhesion and spreading, which was consistent with the results of miR-30b-5p overexpression. Further in vivo experiments demonstrated that miR-30b-5p overexpression inhibited CRLM, but Rap1b rescue attenuated the inhibitory effect of miR-30b-5p. In addition, miR-30b-5p was downregulated in CRC specimens, and Rap1b showed a negative correlation with miR-30b-5p expression in primary CRC and LM tissues. These results indicate that miR-30b-5p functions as a metastasis suppressor by targeting Rap1b and may provide a new target for the treatment of CRLM.

miR-200c Modulates the Pathogenesis of Radiation-Induced Oral Mucositis.

Radiation-induced oral mucositis (RIOM) is one of the most common side effects of radiotherapy in cancer patients, especially in almost all head and neck cancer patients. It presents as severe pain and ulceration. The development of RIOM is composed of five stages: initiation, primary damage response, signal amplification, ulceration, and healing. However, the key regulators involved in the RIOM pathogenesis remain largely unknown. In this study, we reveal a novel role of miR-200c, a member of the miR-200 family, in modulating RIOM pathogenesis. Using a mouse model mimicking RIOM, we found that the miR-200 family numbers (miR-141, miR-200a, miR-200b, and miR-200c) except miR-429 were significantly induced during the RIOM formation. Besides, in RIOM mice, miR-200c expression level was also increased dramatically in the normal human keratinocytes (NHKs) after irradiation. Knockdown of miR-200c expression with miR-200c-3p-shRNA significantly reduced senescence phenotype and enhanced cell proliferation in NHKs after irradiation. The generation of reactive oxygen species (ROS) and p47 enzyme involved in ROS production was increased after irradiation but both were markedly reduced in NHKs by miR-200c inhibition. Knockdown of miR-200c expression in NHKs increased DNA double-strand break repair after irradiation compared with control NHKs. Furthermore, miR-200c inhibition repressed the production of proinflammatory cytokines (TGF-ß, TNF-α, and IL-1α) via inhibiting NF-κB and Smad2 activation in NHKs exposed to IR. Additionally, miR-200c inhibition promoted NHK migration and increased the expression of molecules that regulate epithelial to mesenchymal transition, including Snail, Vimentin, Zeb1, and Bmi-1. These results not only identify the key role of miR-200c in the pathogenesis of RIOM but also provide a novel therapeutic target to treat RIOM.