Optically Readable, Physically Unclonable Subwavelength Pixel via Multicolor Quantum Dot Printing for Anticounterfeiting.

We present a secure and user-friendly ultraminiaturized anticounterfeiting labeling technique─the color-encoded physical unclonable nanotag. These nanotags consist of subwavelength spots formed by random combinations of multicolor quantum dots, which are fabricated using a cost-efficient printing method developed in this study. The nanotags support over 170,000 different colors and are inherently resistant to cloning. Moreover, their high brightness and color purity, owing to the quantum dots, ensure an ease of readability. Additionally, these nanotags can function as color-encrypted pixels, enabling the incorporation of labels (such as QR codes) into ultrasmall physically unclonable hidden tags with a resolution exceeding 100,000 DPI. The unique blend of compactness, flexibility, and security positions the color-encoded nanotag as a potent and versatile solution for next-generation anticounterfeiting applications.

DYNLL1 binds to MRE11 to limit DNA end resection in BRCA1-deficient cells.

Limited DNA end resection is the key to impaired homologous recombination in BRCA1-mutant cancer cells. Here, using a loss-of-function CRISPR screen, we identify DYNLL1 as an inhibitor of DNA end resection. The loss of DYNLL1 enables DNA end resection and restores homologous recombination in BRCA1-mutant cells, thereby inducing resistance to platinum drugs and inhibitors of poly(ADP-ribose) polymerase. Low BRCA1 expression correlates with increased chromosomal aberrations in primary ovarian carcinomas, and the junction sequences of somatic structural variants indicate diminished homologous recombination. Concurrent decreases in DYNLL1 expression in carcinomas with low BRCA1 expression reduced genomic alterations and increased homology at lesions. In cells, DYNLL1 limits nucleolytic degradation of DNA ends by associating with the DNA end-resection machinery (MRN complex, BLM helicase and DNA2 endonuclease). In vitro, DYNLL1 binds directly to MRE11 to limit its end-resection activity. Therefore, we infer that DYNLL1 is an important anti-resection factor that influences genomic stability and responses to DNA-damaging chemotherapy.

Smart Magnetic Optical Antenna for Automatic Nanoalignment and Photon Beaming from Prepatterned Single Quantum Dot Nanospot.

We present a unidirectional dielectric optical antenna, which can be chemically synthesized and controlled by magnetic fields. By applying magnetic fields, we successfully aligned an optical antenna on a prepatterned quantum dot nanospot with accuracy better than 40 nm. It confined the fluorescence emission into a 16-degree wide beam and enhanced the signal by 11.8 times. Moreover, the position of the antenna, and consequently the beam direction, can be controlled by simply adjusting the direction of the magnetic fields. Theoretical analyses show that this magnetic alignment technique is stable and accurate, providing a new strategy for building high-performance tunable nanophotonic devices.

In Situ Fluorescence Imaging Reveals Contribution of Cerebral Hydroxyl Radicals in Hyperhomocysteinemia-Induced Alzheimer-like Dementia.

Elevated plasma level of homocysteine, also termed as hyperhomocysteinemia, is acknowledged as a significant and independent risk factor of Alzheimer's disease. However, the mechanistic insight has not been thoroughly elucidated yet. In this work, 3,5-dihydroxybenzyloxy was explored as the unique reaction trigger and integrated into the naphthalimide fluorophore via a carbamate linker to afford a new probe for •OH imaging. •OH treatment induced aromatic hydroxylation and subsequent elimination reaction to release the caged fluorophore, accompanied with a highly specific and sensitive turn-on fluorescence response. Cell imaging results revealed that excess homocysteine triggered overwhelming •OH production, which was mediated by N-methyl-d-aspartate receptor and NADPH oxidase, and the resultant •OH stress further initiated neuronal ferroptosis, also confirmed by western blot analyses. Additionally, hyperhomocysteinemic mouse models were established, and Alzheimer-like dementia of the mice was observed from behavioral tests. Most importantly, with this probe, cerebral •OH fluctuation was in situ visualized in live mice, which positively correlated with the severity of Alzheimer-like dementia induced by hyperhomocysteinemia. These results reveal that cerebral •OH stress may be the critical nexus linking hyperhomocysteinemia and Alzheimer's disease. This work provides a robust fluorescence probe for in situ visualizing the cerebral •OH fluctuations and illuminating critical insights into •OH contributions in brain disorders.

Immunized Microspheres Engineered Hydrogel Membrane for Reprogramming Macrophage and Mucosal Repair.

The "double-edged sword" effect of macrophages under the influence of different microenvironments determines the outcome and prognosis of tissue injury. Accurate and stable reprogramming macrophages (Mφ) are the key to rapid wound healing. In this study, an immunized microsphere-engineered GelMA hydrogel membrane is constructed for oral mucosa treatment. The nanoporous poly(lactide-co-glycolide) (PLGA) microsphere drug delivery system combined with the photo-cross-linkable hydrogel is used to release the soybean lecithin (SL)and IL-4 complexes (SL/IL-4) sustainedly. In this way, it is realized effective wound fit, improvement of drug encapsulation, and stable triphasic release of interleukin-4 (IL-4). In both in vivo and in vitro experiments, it is demonstrated that the hydrogel membrane can reprogram macrophages in the microenvironment into M2Mφ anti-inflammatory types, thereby inhibiting the local excessive inflammatory response. Meanwhile, high levels of platelet-derived growth factor (PDGF) secreted by M2Mφ macrophages enhanced neovascular maturation by 5.7-fold, which assisted in achieving rapid healing of oral mucosa. These findings suggest that the immuno-engineered hydrogel membrane system can re-modulating the biological effects of Mφ, and potentiating the maturation of neovascularization, ultimately achieving the rapid repair of mucosal tissue. This new strategy is expected to be a safe and promising immunomodulatory biomimetic material for clinical translation.

Photocontrollable Fluorescence Imaging of Mitochondrial Peroxynitrite during Ferroptosis with High Fidelity.

Ferroptosis, a new regulatory cell death modality, underlies the pathogenesis of a broad range of disorders. Although much efforts have been made to uncover the molecular mechanisms, some mechanistic details of ferroptosis still remain poorly understood. Particularly, the functional relevance of mitochondrial reactive oxygen species (ROS) in ferroptosis is still highly controversial, which is partially due to the fact that it still remains puzzled how the mitochondrial ROS level varies during ferroptosis. The conventional mitochondria-targeted probes may react with cytosolic ROS and show fluorescence variation before entering mitochondria, thus probably giving a false result on the mitochondrial ROS level and leading to the misjudgment on its biofunction. To circumvent this issue, we rationally designed a photocontrollable and mitochondria-targeted fluorescent probe to in situ visualize the mitochondrial peroxynitrite (ONOO-), which is the ROS member and mediator of ferroptosis. The photoactivated probe was endowed with a highly specific and sensitive fluorescence response to ONOO-. Notably, the response activity could be artificially regulated with light irradiation, which ensured that all the probe molecules passed through the cytosol in the locked status and were then photoactivated after reaching mitochondria. This photocontrolled fluorescence imaging strategy eliminated the interference of ONOO- outside the mitochondria, thus potentially afforded improved fidelity for mitochondrial ONOO- bioimaging in live cells and animal models. With this probe, for the first time, we revealed the mitochondrial ONOO- flux and its probable biological source during erastin-induced ferroptosis. These results suggest a tight correlation between mitochondrial ONOO-/ROS and ferroptotic progression, which will further facilitate the comprehensive exploration and manipulation of ferroptosis.

Overall diagnostic accuracy of different MR imaging sequences for detection of dysplastic nodules: a systematic review and meta-analysis.

OBJECTIVE: To assess the overall diagnostic accuracy of different MR imaging sequences in the detection of the dysplastic nodule (DN). METHODS: PubMed, Cochrane Library, and Web of Science were systematically searched. Study selection and data extraction were conducted by two authors independently. Quality assessment of diagnostic accuracy studies (QUADAS) 2 in RevMan software was used to score the included studies and assess their methodological quality. A random-effects model was used for statistical pooling by Meta-Disc. Subgroup analysis and sensitivity analysis were used to explore potential sources of heterogeneity. RESULTS: Fourteen studies (335 DN lesions in total) were included in our meta-analysis. The area under the curve (AUC) of summary receiver operating characteristic (SROC) of T2WI was 0.87. Pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of DWI were 0.81 (95%CI, 0.73-0.87), 0.90 (95%CI, 0.86-0.93), 7.04 (95%CI, 4.49-11.04), and 0.24 (95%CI, 0.17-0.33) respectively. In the arterial phase, pooled sensitivity, specificity, PLR, and NLR were 0.89 (0.84-0.93), 0.75 (0.72-0.79), 3.72 (2.51-5.51), and 0.17 (0.12-0.25), respectively. Pooled sensitivity, specificity, PLR, and NLR of the delayed phase were 0.78 (0.72-0.83), 0.60 (0.55-0.65), 2.19 (1.55-3.10), and 0.36 (0.23-0.55) separately. Pooled sensitivity, specificity, PLR, and NLR of the hepatobiliary phase were 0.77 (0.71-0.82), 0.92 (0.89-0.94), 8.74 (5.91-12.92), and 0.24 (0.14-0.41) respectively. Pooled sensitivity, specificity, and PLR were higher on DWI and hepatobiliary phase in diagnosing LGDN than HGDN. CONCLUSION: MR sequences, particularly DWI, arterial phase, and hepatobiliary phase imaging demonstrate high diagnostic accuracy for DN. KEY POINTS: • MRI has dramatically improved the detection and accurate diagnosis of DNs and their differentiation from hepatocellular carcinoma. • Overall diagnostic accuracy of different MRI sequences in the detection of DN has not been studied before. • Our meta-analysis demonstrates that MRI achieves a high diagnostic value for DN, especially when using DWI, arterial phase imaging, and hepatobiliary phase imaging.

Bacteria-engineered porous sponge for hemostasis and vascularization.

BACKGROUND: Hemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner. RESULTS: In this study, we constructed a hemostatic sponge OBNC-DFO by fermentation of Komagataeibacter xylinus combined with TEMPO oxidation to obtain oxidized bacterial nanocellulose (OBNC). Then angiogenetic drug desferrioxamine (DFO) was grafted through an amide bond, and it promoted clot formation and activated coagulation reaction by rapid blood absorption due to the high total pore area (approximately 42.429 m2/g measured by BET). The further release of DFO stimulated the secretion of HIF-1α and the reconstruction of blood flow, thus achieving rapid hemostasis and vascularization in damaged tissue. This new hemostatic sponge can absorb water at a rate of approximate 1.70 g/s, rapidly enhancing clot formation in the early stage of hemostasis. In vitro and in vivo coagulation experiments (in rat tail amputation model and liver trauma model) demonstrated superior pro-coagulation effects of OBNC and OBNC-DFO to clinically used collagen hemostatic sponges (COL). They promoted aggregation and activation of red blood cells and platelets with shorter whole blood clotting time, more robust activation of endogenous coagulation pathways and less blood loss. In vitro cellular assays showed that OBNC-DFO prevailed over OBNC by promoting the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the release of DFO enhanced the secretion of HIF-1α, further strengthening vascularization in damaged skin. In the rat skin injury model, 28 days after being treated with OBNC-DFO, skin appendages (e.g., hair follicles) became more intact, indicating the achievement of structural and functional regeneration of the skin. CONCLUSION: This hemostatic and vascularization-promoting oxidized bacterial nanocellulose hemostatic sponge, which rapidly activates coagulation pathways and enables skin regeneration, is a highly promising hemostatic and pro-regenerative repair biomaterial.

Sensing of mercury and silver ions using branched Au nanoparticles prepared by hyperbranched polyethylenimine fabricated and capped AuNPs seeds.

Branched AuNPs usually have two or more local surface plasmon resonance (LSPR) absorption bands due to their structural anisotropy, and the LSPR performance is more sensitive to the changes of environmental refractive index than that of spherical AuNPs. The design and preparation of branched AuNPs as colorimetric probes is expected to improve the selectivity and sensitivity of detection of targets. In this paper, branched AuNPs were innovatively synthesized via hyperbranched polyethylenimine (HPEI) fabricated and capped AuNPs as seeds and cetyltrimethylammonium bromide (CTAB) as template agent. The branched AuNPs were characterized by TEM, DLS, zeta potentials and UV-vis spectra. Using the branched AuNPs as a colorimetric probe, the detection system for Hg2+and Ag+showed bright color changes from blue to orange and blue to green based on the morphological evolution of branched AuNPs. The branched AuNPs could selectively detect Hg2+and Ag+at concentrations as low as 77 and 140 nM, respectively. Moreover, this unusual colorimetric method has been successfully used in real water samples and has great potential as a simple, rapid, sensitive and selective method for the detection of Hg2+and Ag+.

Clinical application of gelatin sponge microparticles combined with pirarubicin for hepatic transcatheter arterial chemoembolization in breast cancer liver metastasis treatment: results of a single-center long-term study.

OBJECTIVE: To retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM). METHODS: Twenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed. RESULTS: By October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant. CONCLUSIONS: The overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application.

Diagnosis of Invasive Lung Adenocarcinoma Based on Chest CT Radiomic Features of Part-Solid Pulmonary Nodules: A Multicenter Study.

Background Solid components of part-solid nodules (PSNs) at CT are reflective of invasive adenocarcinoma, but studies describing radiomic features of PSNs and the perinodular region are lacking. Purpose To develop and to validate radiomic signatures diagnosing invasive lung adenocarcinoma in PSNs compared with the Brock, clinical-semantic features, and volumetric models. Materials and Methods This retrospective multicenter study (https://ClinicalTrials.gov, NCT03872362) included 291 patients (median age, 60 years; interquartile range, 55-65 years; 191 women) from January 2013 to October 2017 with 297 PSN lung adenocarcinomas split into training (n = 229) and test (n = 68) data sets. Radiomic features were extracted from the different regions (gross tumor volume [GTV], solid, ground-glass, and perinodular). Random-forest models were trained using clinical-semantic, volumetric, and radiomic features, and an online nodule calculator was used to compute the Brock model. Performances of models were evaluated using standard metrics such as area under the curve (AUC), accuracy, and calibration. The integrated discrimination improvement was applied to assess model performance changes after the addition of perinodular features. Results The radiomics model based on ground-glass and solid features yielded an AUC of 0.98 (95% confidence interval [CI]: 0.96, 1.00) on the test data set, which was significantly higher than the Brock (AUC, 0.83 [95% CI: 0.72, 0.94]; P = .007), clinical-semantic (AUC, 0.90 [95% CI: 0.83, 0.98]; P = .03), volumetric GTV (AUC, 0.87 [95% CI: 0.78, 0.96]; P = .008), and radiomics GTV (AUC, 0.88 [95% CI: 0.80, 0.96]; P = .01) models. It also achieved the best accuracy (93% [95% CI: 84%, 98%]). Both this model and the model with added perinodular features showed good calibration, whereas adding perinodular features did not improve the performance (integrated discrimination improvement, -0.02; P = .56). Conclusion Separating ground-glass and solid CT radiomic features of part-solid nodules was useful in diagnosing the invasiveness of lung adenocarcinoma, yielding a better predictive performance than the Brock, clinical-semantic, volumetric, and radiomics gross tumor volume models. Online supplemental material is available for this article. See also the editorial by Nishino in this issue. Published under a CC BY 4.0 license.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Evaluation of the Cell Density and Angiogenesis of Cirrhosis-Related Nodules in an Experimental Rat Model: Comparison and Correlation With Dynamic Contrast-Enhanced MRI.

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced MRI (DCE-MRI) are sensitive imaging modalities for detecting liver lesions, but their value in evaluating cirrhosis-related nodules remains unclear. PURPOSE: To investigate whether IVIM-DWI and DCE-MRI can differentiate different types of cirrhosis-related nodules, and whether these modalities can monitor changes in cell density and angiogenesis during the malignant transformation of cirrhosis-related nodules in a rat model STUDY TYPE: Prospective. ANIMAL MODEL: Thirty-five male Sprague-Dawley rats with 106 cirrhosis-related nodules (19 regenerative nodules [RNs], 47 dysplastic nodules [DNs], and 40 hepatocellular carcinomas [HCCs]). FIELD STRENGTH/SEQUENCE: IVIM-DWI and DCE sequence at 3.0T MRI. ASSESSMENT: IVIM-DWI parameters (D, D*, f, and apparent diffusion coefficient [ADC]) and DCE-MRI parameters (Ktrans , Kep , and Ve ) were calculated by two radiologists using postprocessing software. The "cell density" and "unpaired arterial ratio" were analyzed with a microscope by two pathologists. STATISTICAL TESTS: MRI parameters were compared among the different types of nodules by one-way analysis of variance or the Kruskal-Wallis test. The Pearson correlation test was used to analyze the correlation of MRI parameters with the pathological types of nodules, cell density, and unpaired arterial ratio. RESULTS: The Ktrans , Kep , and Ve values of HCCs were significantly higher than those of DNs and RNs. D and ADC values were significantly lower in HCCs than in DNs and RNs. There were moderate positive correlations of Ktrans with the pathological types of nodules and the unpaired arterial ratio. Moderate negative correlations were observed among D, ADC, and the pathological types of nodules, between D and cell density, and between ADC and cell density. DATA CONCLUSION: IVIM-DWI and DCE-MRI are valuable in differentiating different types of cirrhotic-related nodules. D and ADC are correlated with changes in cell density during the malignant transformation of cirrhosis-related nodules, while Ktrans is correlated with increased angiogenesis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:812-823.

Preoperative CT-based radiomics combined with intraoperative frozen section is predictive of invasive adenocarcinoma in pulmonary nodules: a multicenter study.

OBJECTIVES: Develop a CT-based radiomics model and combine it with frozen section (FS) and clinical data to distinguish invasive adenocarcinomas (IA) from preinvasive lesions/minimally invasive adenocarcinomas (PM). METHODS: This multicenter study cohort of 623 lung adenocarcinomas was split into training (n = 331), testing (n = 143), and external validation dataset (n = 149). Random forest models were built using selected radiomics features, results from FS, lesion volume, clinical and semantic features, and combinations thereof. The area under the receiver operator characteristic curves (AUC) was used to evaluate model performances. The diagnosis accuracy, calibration, and decision curves of models were tested. RESULTS: The radiomics-based model shows good predictive performance and diagnostic accuracy for distinguishing IA from PM, with AUCs of 0.89, 0.89, and 0.88, in the training, testing, and validation datasets, respectively, and with corresponding accuracies of 0.82, 0.79, and 0.85. Adding lesion volume and FS significantly increases the performance of the model with AUCs of 0.96, 0.97, and 0.96, and with accuracies of 0.91, 0.94, and 0.93 in the three datasets. There is no significant difference in AUC between the FS model enriched with radiomics and volume against an FS model enriched with volume alone, while the former has higher accuracy. The model combining all available information shows minor non-significant improvements in AUC and accuracy compared with an FS model enriched with radiomics and volume. CONCLUSIONS: Radiomics signatures are potential biomarkers for the risk of IA, especially in combination with FS, and could help guide surgical strategy for pulmonary nodules patients. KEY POINTS: • A CT-based radiomics model may be a valuable tool for preoperative prediction of invasive adenocarcinoma for patients with pulmonary nodules. • Radiomics combined with frozen sections could help in guiding surgery strategy for patients with pulmonary nodules.

Tailoring a nanostructured plasmonic absorber for high efficiency surface-assisted laser desorption/ionization.

The surface-assisted laser desorption/ionization (SALDI) effect is investigated on Au plated anodized aluminum oxide (Au/AAO) thin films, a new type of low-cost broadband plasmonic absorber, which has attracted a lot of attention recently. Mass spectrometry (MS) measurements show that the ionization efficiency of Au/AAO substrates can be significantly improved (×30 fold) by simply tuning the size of nanopores in Au/AAOs. This leads to a signal-to-noise ratio of 394, which is 4 times better than the result obtained using the conventional matrix-assisted laser desorption/ionization (MALDI)-MS technique. Experimental and theoretical studies show that the dramatic improvement is caused by the pore-size-dependent optical and thermal properties of Au/AAOs. It provides a simple yet effective strategy for designing and building high performance plasmonic SALDI substrates.

Aquaporin-4 knockdown ameliorates hypoxic-ischemic cerebral edema in newborn piglets.

Emerging evidence indicates that the water channel protein aquaporin 4 (AQP4) plays an essential role in water homeostasis and is implicated in the pathogenesis of brain edema. This study aimed to understand the physiological role of AQP4 in hypoxia-ischemia-mediated cytotoxic brain edema. We specifically knocked down AQP4 expression by intracerebral injection of a plasmid containing AQP4 siRNA into a neonatal piglet model. The success of the hypoxia-ischemia-induced piglet model was confirmed by conventional magnetic resonance imaging and diffusion-weighted imaging. AQP4 knockdown led to reduced brain edema accompanied by a higher apparent diffusion coefficient value, compared to the control group injected with a plasmid containing scrambled siRNA. Real-time polymerase chain reaction and immunohistochemical analysis confirmed that AQP4 siRNA significantly reduced AQP4 mRNA and protein expression. Finally, neurological function analysis revealed that AQP4 knockdown significantly improved neurobehavioral manifestation of the piglets after exposure to hypoxia-ischemia. Taken together, these results indicate that AQP4 plays an important role in mediating brain edema in hypoxic-ischemic encephalopathy. Therefore, AQP4 could be a therapeutic target to ameliorate early-stage brain edema.

miR-26a-5p Attenuates Oxidative Stress and Inflammation in Diabetic Retinopathy through the USP14/NF-κB Signaling Pathway.

Purpose: Diabetic retinopathy (DR) is an ocular disease caused by diabetes and may lead to vision impairment and even blindness. Oxidative stress and inflammation are two key pathogenic factors of DR. Recently, regulatory roles of different microRNAs (miRNAs) in DR have been widely verified. miR-26a-5p has been confirmed to be a potential biomarker of DR. Nevertheless, the specific functions of miR-26a-5p in DR are still unclear. Methods: Primary cultured mouse retinal Müller cells in exposure to high glucose (HG) were used to establish an in vitro DR model. Müller cells were identified via morphology observation under phase contrast microscope and fluorescence staining for glutamine synthetase. The in vivo animal models for DR were constructed using streptozotocin-induced diabetic C57BL/6 mice. Western blotting was performed to quantify cytochrome c protein level in the cytoplasm and mitochondria of Müller cells and to measure protein levels of glial fibrillary acidic protein (GFAP), ubiquitin-specific peptidase 14 (USP14), as well as factors associated with NF-κB signaling (p-IκBα, IκBα, p-p65, and p65) in Müller cells or murine retinal tissues. ROS production was detected by CM-H2DCFDA staining, and the concentration of oxidative stress markers (MDA, SOD, and CAT) was estimated by using corresponding commercial kits. Quantification of mRNA expression was conducted by RT-qPCR analysis. The concentration of proinflammatory factors (TNF-α, IL-1ß, and IL-6) was evaluated by ELISA. Hematoxylin-eosin staining for murine retinal tissues was performed for histopathological analysis. Immunofluorescence staining was conducted to determine NF-κB p65 nuclear translocation in Müller cells. Furthermore, the interaction between miR-26a-5p and USP14 was verified via the luciferase reporter assays. Results: HG stimulation contributed to Müller cell dysfunction by inducing inflammation, oxidative injury, and mitochondrial damage to Müller cells. miR-26a-5p was downregulated in Müller cells under HG condition, and overexpression of miR-26a-5p relieved HG-induced Müller cell dysfunction. Moreover, miR-26a-5p targeted USP14 and inversely regulated USP14 expression. Additionally, HG-evoked activation of NF-κB signaling was suppressed by USP14 knockdown or miR-26a-5p upregulation. Rescue assays showed that the protective impact of miR-26a-5p upregulation against HG-induced Müller cell dysfunction was reversed by USP14 overexpression. Furthermore, USP14 upregulation and activation of NF-κB signaling in the retinas of DR mice were detected in animal experiments. Injection with miR-26a-5p agomir improved retinal histopathological injury and weakened the concentration of proinflammatory cytokines and oxidative stress markers in the retinas of DR mice. Conclusion: miR-26a-5p inhibits oxidative stress and inflammation in DR progression by targeting USP14 and inactivating the NF-κB signaling pathway.

Prognostic significance of USP22 as an oncogene in papillary thyroid carcinoma.

Ubiquitin-specific protease 22 (USP22), a novel deubiquitinating enzyme, has been associated with metastasis, therapy resistance, and cell cycle progression. The purpose of this study was to investigate the expression level of USP22 in papillary thyroid carcinoma (PTC) samples and to evaluate its clinical significance in PTC patients. USP22 expression was examined in 30 fresh PTC tissues and paired adjacent noncancerous tissues by real-time quantitative RT-PCR. Immunohistochemistry for USP22 was performed on additional 156 PTC tissues. The clinical significance of USP22 expression was analyzed. We found that the expression levels of USP22 mRNA and protein in PTC tissues were both significantly higher than those in noncancerous tissues. Clinicopathological analysis showed that USP22 expression was significantly correlated with tumor size (p=0.036), extracapsular invasion (p=0.012), multifocality (p=0.014), lymph node metastasis (p=0.022), distant metastasis (p=0.005), and TNM stage (p=0.002). The Kaplan-Meier survival curves revealed that USP22 expression was associated with poor prognosis in PTC patients. USP22 expression was an independent prognostic marker of overall patient survival in a multivariate analysis. Our findings suggest that USP22 is an independent predictor of poor prognosis of PTC patients.

Double transfer UV-curing nanoimprint lithography.

A challenge in the fabrication of nanostructures into non-planar substrates is to form a thin, uniform resist film on non-planar surfaces. This is critical to the fabrication of nanostructures via a lithographic technique due to the subsequent pattern transfer process. Here we report a new double transfer UV-curing nanoimprint technique that can create a nanopatterned thin film with a uniform residual layer not only on flat substrates but also on highly curved surfaces. Surface relief gratings with pitches down to 200 nm are successfully imprinted on the cylindrical surface of optical fibers, and further transferred into a SiO2 matrix using reactive ion etching (RIE), demonstrating that our technique is applicable for fabricating high-resolution nanostructures on non-planar substrates.

Radiomics signatures based on contrast-enhanced CT for preoperative prediction of the Ki-67 proliferation state in gastrointestinal stromal tumors.

PURPOSE: This study aimed to evaluate the Ki-67 proliferation state in patients with gastrointestinal stromal tumors (GISTs) using radiomics prediction signatures based on contrast-enhanced computed tomography (CE-CT). MATERIALS AND METHODS: This single-center, retrospective study involved 103 patients (48 men and 55 women, mean age 61.1 ± 10.6 years) who had pathologically confirmed GISTs after curative resection, including 63 with low Ki-67 proliferation level (Ki-67 labeling index ≤ 6%) and 40 with high Ki-67 proliferation level (Ki-67 labeling index > 6%). Radiomics features of the delineated lesions were preoperatively extracted from three-phase CE-CT images, including the arterial, venous, and delayed phases. The most relevant features were selected to construct the radiomics signatures using a logistic regression algorithm. Significant demographic characteristics and semantic features on CT were selected to develop a nomogram along with the optimal radiomics feature. We calculated the sensitivity, specificity, accuracy, F1 score, and area under the receiver operating characteristic (ROC) curve to evaluate the predictive performance of radiomics signatures. RESULTS: Ten quantitative radiomics features (two first-order and eight texture features) were selected to construct radiomics signatures. The radiomics signature based on the three-phase CE-CT images showed better predictive performance than that based on the single-phase CE-CT images, with an area under the curve (AUC) of 0.83 (95% CI 0.73-0.92) and F1 score of 82% in the training dataset and an AUC of 0.80 (95% CI 0.63-0.95) and F1 score of 75% in the testing dataset. The nomogram showed good calibration. CONCLUSION: Radiomics signatures using CE-CT images are generalizable and could be used in clinical practice to determine the proliferation state of Ki-67 in GISTs.