DSTAN: A Deformable Spatial-temporal Attention Network with Bidirectional Sequence Feature Refinement for Speckle Noise Removal in Thyroid Ultrasound Video.

Thyroid ultrasound video provides significant value for thyroid diseases diagnosis, but the ultrasound imaging process is often affected by the speckle noise, resulting in poor quality of the ultrasound video. Numerous video denoising methods have been proposed to remove noise while preserving texture details. However, existing methods still suffer from the following problems: (1) relevant temporal features in the low-contrast ultrasound video cannot be accurately aligned and effectively aggregated by simple optical flow or motion estimation, resulting in the artifacts and motion blur in the video; (2) fixed receptive field in spatial features integration lacks the flexibility of aggregating features in the global region of interest and is susceptible to interference from irrelevant noisy regions. In this work, we propose a deformable spatial-temporal attention denoising network to remove speckle noise in thyroid ultrasound video. The entire network follows the bidirectional feature propagation mechanism to efficiently exploit the spatial-temporal information of the whole video sequence. In this process, two modules are proposed to address the above problems: (1) a deformable temporal attention module (DTAM) is designed after optical flow pre-alignment to further capture and aggregate relevant temporal features according to the learned offsets between frames, so that inter-frame information can be better exploited even with the imprecise flow estimation under the low contrast of ultrasound video; (2) a deformable spatial attention module (DSAM) is proposed to flexibly integrate spatial features in the global region of interest through the learned intra-frame offsets, so that irrelevant noisy information can be ignored and essential information can be precisely exploited. Finally, all these refined features are rectified and merged through residual convolution blocks to recover the clean video frames. Experimental results on our thyroid ultrasound video (US-V) dataset and the DDTI dataset demonstrate that our proposed method exceeds 1.2 ∼ 1.3 dB on PSNR and has clearer texture detail compared to other state-of-the-art methods. In the meantime, the proposed model can also assist thyroid nodule segmentation methods to achieve more accurate segmentation effect, which provides an important basis for thyroid diagnosis. In the future, the proposed model can be improved and extended to other medical image sequence datasets, including CT and MRI slice denoising. The code and datasets are provided at https://github.com/Meta-MJ/DSTAN .

Applying machine-learning models to differentiate benign and malignant thyroid nodules classified as C-TIRADS 4 based on 2D-ultrasound combined with five contrast-enhanced ultrasound key frames.

Objectives: To apply machine learning to extract radiomics features from thyroid two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasound (CEUS) images to classify and predict benign and malignant thyroid nodules, classified according to the Chinese version of the thyroid imaging reporting and data system (C-TIRADS) as category 4. Materials and methods: This retrospective study included 313 pathologically diagnosed thyroid nodules (203 malignant and 110 benign). Two 2D-US images and five CEUS key frames ("2nd second after the arrival time" frame, "time to peak" frame, "2nd second after peak" frame, "first-flash" frame, and "second-flash" frame) were selected to manually label the region of interest using the "Labelme" tool. A total of 7 images of each nodule and their annotates were imported into the Darwin Research Platform for radiomics analysis. The datasets were randomly split into training and test cohorts in a 9:1 ratio. Six classifiers, namely, support vector machine, logistic regression, decision tree, random forest (RF), gradient boosting decision tree and extreme gradient boosting, were used to construct and test the models. Performance was evaluated using a receiver operating characteristic curve analysis. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC), and F1-score were calculated. One junior radiologist and one senior radiologist reviewed the 2D-US image and CEUS videos of each nodule and made a diagnosis. We then compared their AUC and ACC with those of our best model. Results: The AUC of the diagnosis of US, CEUS and US combined CEUS by junior radiologist and senior radiologist were 0.755, 0.750, 0.784, 0.800, 0.873, 0.890, respectively. The RF classifier performed better than the other five, with an AUC of 1 for the training cohort and 0.94 (95% confidence interval 0.88-1) for the test cohort. The sensitivity, specificity, accuracy, PPV, NPV, and F1-score of the RF model in the test cohort were 0.82, 0.93, 0.90, 0.85, 0.92, and 0.84, respectively. The RF model with 2D-US combined with CEUS key frames achieved equivalent performance as the senior radiologist (AUC: 0.94 vs. 0.92, P = 0.798; ACC: 0.90 vs. 0.92) and outperformed the junior radiologist (AUC: 0.94 vs. 0.80, P = 0.039, ACC: 0.90 vs. 0.81) in the test cohort. Conclusions: Our model, based on 2D-US and CEUS key frames radiomics features, had good diagnostic efficacy for thyroid nodules, which are classified as C-TIRADS 4. It shows promising potential in assisting less experienced junior radiologists.

Reduced lysosomal density in neuronal dendrites mediates deficits in synaptic plasticity in Huntington's disease.

Huntington's disease (HD) usually causes cognitive disorders, including learning difficulties, that emerge before motor symptoms. Mutations related to lysosomal trafficking are linked to the pathogenesis of neurological diseases, whereas the cellular mechanisms remain elusive. Here, we discover a reduction in the dendritic density of lysosomes in the hippocampus that correlates with deficits in synaptic plasticity and spatial learning in early CAG-140 HD model mice. We directly manipulate intraneuronal lysosomal positioning with light-induced CRY2:CIB1 dimerization and demonstrate that lysosomal abundance in dendrites positively modulates long-term potentiation of glutamatergic synapses onto the neuron. This modulation depends on lysosomal Ca2+ release, which further promotes endoplasmic reticulum (ER) entry into spines. Importantly, optogenetically restoring lysosomal density in dendrites rescues the synaptic plasticity deficit in hippocampal slices of CAG-140 mice. Our data reveal dendritic lysosomal density as a modulator of synaptic plasticity and suggest a role of lysosomal mispositioning in cognitive decline in HD.

Efficacy and safety of cyclin-dependent kinase 4/6 inhibitor in patients with advanced breast cancer: A real-world experience.

BACKGROUND: Cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) have been shown to improve progression-free survival (PFS) in patients with metastatic breast cancer (MBC) in randomized control trials. This study aimed to evaluate the efficacy and safety of CDK4/6i in patients with advanced breast cancer (ABC) in a clinical setting. METHODS: Consecutive patients with ABC were treated between October 2019 and March 2023 at Taipei Tzu Chi Hospital, Taiwan. Patients who had received at least one dose of CDK4/6i were included in this retrospective study. The main outcome of this study was efficacy based on the treating physicians' assessments in terms of PFS, and overall survival (OS), as well as the factors associated with patient outcome. The secondary outcome was safety. RESULTS: A total of 85 patients were included in the analysis, with a mean age of 66.8 years. After a median follow-up of 16.1 months, the median PFS was 28.4 months (95% CI: 22.5-33.6) and the median OS could not yet be estimated. The most common adverse events (AE) were fatigue (50.8%), anorexia (45.9%), and leukopenia (44.7%). In multivariable analysis, treatment with CDK4/6i with any grade AE or response to treatment effect (CR/PR) was an independent predictor for longer PFS (hazard ratio [HR] = 0.27, 95% CI: 0.11-0.68; HR = 0.21, 95% CI: 0.06-0.67; p < 0.05). CONCLUSION: CDK4/6i administered in a real-world setting exhibits a similar survival benefit with the clinical trials.

The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission.

Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) and Mdv1 (the bridging protein between Fis1 and Dnm1), from mitochondria and reduces the localization of Dnm1 to mitochondria. The effect of Yta4 overexpression on Fis1 and Mdv1, but not Dnm1, depends on the ATPase and translocase activities of Yta4. Moreover, Yta4 interacts with Dnm1, Mdv1, and Fis1. In addition, Yta4 competes with Dnm1 for binding Mdv1 and decreases the affinity of Dnm1 for GTP and inhibits Dnm1 assembly in vitro. These findings suggest a model, in which Yta4 inhibits mitochondrial fission by inhibiting the function of the mitochondrial divisome composed of Fis1, Mdv1, and Dnm1. Therefore, the present work reveals an uncharacterized molecular mechanism underlying the inhibition of mitochondrial fission.

Nanoscale reorganisation of synaptic proteins in Alzheimer's disease.

AIMS: Synaptic strength depends strongly on the subsynaptic organisation of presynaptic transmitter release and postsynaptic receptor densities, and their alterations are expected to underlie pathologies. Although synaptic dysfunctions are common pathogenic traits of Alzheimer's disease (AD), it remains unknown whether synaptic protein nano-organisation is altered in AD. Here, we systematically characterised the alterations in the subsynaptic organisation in cellular and mouse models of AD. METHODS: We used immunostaining and super-resolution stochastic optical reconstruction microscopy imaging to quantitatively examine the synaptic protein nano-organisation in both Aß1-42-treated neuronal cultures and cortical sections from a mouse model of AD, APP23 mice. RESULTS: We found that Aß1-42-treatment of cultured hippocampal neurons decreased the synaptic retention of postsynaptic scaffolds and receptors and disrupted their nanoscale alignment to presynaptic transmitter release sites. In cortical sections, we found that while GluA1 receptors in wild-type mice were organised in subsynaptic nanoclusters with high local densities, receptors in APP23 mice distributed more homogeneously within synapses. This reorganisation, together with the reduced overall receptor density, led to reduced glutamatergic synaptic transmission. Meanwhile, the transsynaptic alignment between presynaptic release-guiding RIM1/2 and postsynaptic scaffolding protein PSD-95 was reduced in APP23 mice. Importantly, these reorganisations were progressive with age and were more pronounced in synapses in close vicinity of Aß plaques with dense cores. CONCLUSIONS: Our study revealed a spatiotemporal-specific reorganisation of synaptic nanostructures in AD and identifies dense-core amyloid plaques as the major local inductor in APP23 mice.

Self-assembly of gelatin and collagen in the polyvinyl alcohol substrate and its influence on cell adhesion, proliferation, shape, spreading and differentiation.

Culture substrates display profound influence on biological and developmental characteristic of cells cultured in vitro. This study investigates the influence of polyvinyl alcohol (PVA) substrates blended with different concentration of collagen or/and gelatin on the cell adhesion, proliferation, shape, spreading, and differentiation of stem cells. The collagen/gelatin blended PVA substrates were prepared by air drying. During drying, blended collagen or/and gelatin can self-assemble into macro-scale nucleated particles or branched fibrils in the PVA substrates that can be observed under the optical microscope. These collagen/gelatin blended substrates revealed different surface topography, z-average, roughness, surface adhesion and Young's modulus as examined by the atomic force microscope (AFM). The results of Fourier transform infrared spectroscopy (FTIR) analysis indicated that the absorption of amide I (1,600-1,700 cm-1) and amide II (1,500-1,600 cm-1) groups increased with increasing collagen and gelatin concentration blended and the potential of fibril formation. These collagen or/and gelatin blended PVA substrates showed enhanced NIH-3T3 fibroblast adhesion as comparing with the pure PVA, control tissue culture polystyrene, conventional collagen-coated and gelatin-coated wells. These highly adhesive PVA substrates also exhibit inhibited cell spreading and proliferation. It is also found that the shape of NIH-3T3 fibroblasts can be switched between oval, spindle and flattened shapes depending on the concentration of collagen or/and gelatin blended. For inductive differentiation of stem cells, it is found that number and ration of neural differentiation of rat cerebral cortical neural stem cells increase with the decreasing collagen concentration in the collagen-blended PVA substrates. Moreover, the PVA substrates blended with collagen or collagen and gelatin can efficiently support and conduct human pluripotent stem cells to differentiate into Oil-Red-O- and UCP-1-positive brown-adipocyte-like cells via ectodermal lineage without the addition of mitogenic factors. These results provide a useful and alternative platform for controlling cell behavior in vitro and may be helpful for future application in the field of regenerative medicine and tissue engineering.

Engineering of NEMO as calcium indicators with large dynamics and high sensitivity.

Genetically encoded calcium indicators (GECIs) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs face the challenge of suboptimal peak signal-to-baseline ratio (SBR) with limited resolution for reporting subtle calcium transients. We report herein the development of a suite of calcium sensors, designated NEMO, with fast kinetics and wide dynamic ranges (>100-fold). NEMO indicators report Ca2+ transients with peak SBRs around 20-fold larger than the top-of-the-range GCaMP6 series. NEMO sensors further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared with GCaMP6s, NEMOs could detect single action potentials in neurons with a peak SBR two times higher and a median peak SBR four times larger in vivo, thereby outperforming most existing state-of-the-art GECIs. Given their high sensitivity and resolution to report intracellular Ca2+ signals, NEMO sensors may find broad applications in monitoring neuronal activities and other Ca2+-modulated physiological processes in both mammals and plants.

Effects of the crown ether cavity on the performance of anion exchange membranes.

Anion exchange membrane fuel cells (AEMFCs) have emerged as a promising alternative to proton exchange membrane fuel cells (PEMFCs) due to their adaptability to low-cost stack components and non-noble-metals catalysts. However, the poor alkaline resistance and low OH- conductivity of anion exchange membranes (AEMs) have impeded the large-scale implementation of AEMFCs. Herein, the preparation of a new type of AEMs with crown ether macrocycles in their main chains via a one-pot superacid catalyzed reaction was reported. The study aimed to examine the influence of crown ether cavity size on the phase separation structure, ionic conductivity and alkali resistance of anion exchange membranes. Attributed to the self-assembly of crown ethers, the poly (crown ether) (PCE) AEMs with dibenzo-18-crown-6-ether (QAPCE-18-6) exhibit an obvious phase separated structure and a maximum OH- conductivity of 122.5 mS cm-1 at 80 °C (ionic exchange capacity is 1.51 meq g-1). QAPCE-18-6 shows a good alkali resistance with the OH- conductivity retention of 94.5% albeit being treated in a harsh alkali condition. Moreover, the hydrogen/oxygen single cell equipped with QAPCE-18-6 can achieve a peak power density (PPD) of 574 mW cm-2 at a current density of 1.39 A cm-2.

Understanding the Origin and Evolution of Tea (Camellia sinensis [L.]): Genomic Advances in Tea.

Tea, which is processed by the tender shoots or leaves of tea plant (Camellia sinensis), is one of the most popular nonalcoholic beverages in the world and has numerous health benefits for humans. Along with new progress in biotechnologies, the refined chromosome-scale reference tea genomes have been achieved, which facilitates great promise for the understanding of fundamental genomic architecture and evolution of the tea plants. Here, we summarize recent achievements in genome sequencing in tea plants and review the new progress in origin and evolution of tea plants by population sequencing analysis. Understanding the genomic characterization of tea plants is import to improve tea quality and accelerate breeding in tea plants.

The lineage-specific evolution of the oleosin family in Theaceae.

Oleosins play essential roles in stabilization of lipid droplets (LDs) and seed oil production. However, evolution of this gene family has not been reported in Theaceae, a large plant family that contains many important tea and oil tea species. In this study, a total of 65 oleosin genes were identified in nine genome-sequenced Theaceae species. Among these genomes, the gene number of oleosin showed significant difference, with Camellia sinensis var. sinensis cv. Shuchazao and Camellia lanceoleosa displayed more oleosin numbers than other species. Phylogenetic analyses revealed that Theaceae oleosin genes were classified into three clades (U, SL, SH) respectively. Proteins within the same clade had similar gene structure and motif composition. Segmental duplication was the primary driving force for the evolution of oleosin genes in Shuchazao (SCZ), Huangdan (HD), C.lanceoleosa (Cla), and wild tea (DASZ). Synteny analysis showed that most oleosin genes displayed inter-species synteny among tea and oil tea species. Expression analysis demonstrated that oleosin genes were specifically expressed in seed and kernel of Huangdan (HD) and C.lanceoleosa. Moreover, expression divergence was observed in paralogous pairs and ∼1-2 oleosin genes in each clade have become activate. This study leads to a comprehensive understanding of evolution of oleosin family in Theaceae, and provides a rich resource to further address the functions of oleosin in tea and oil tea species.

Piezo1 channel activation stimulates ATP production through enhancing mitochondrial respiration and glycolysis in vascular endothelial cells.

BACKGROUND AND PURPOSE: Piezo1 channels are mechanosensitive cationic channels that are activated by mechanical stretch or shear stress. Endothelial Piezo1 activation by shear stress caused by blood flow induces ATP release from endothelial cells; however, the link between shear stress and endothelial ATP production is unclear. EXPERIMENTAL APPROACH: The mitochondrial respiratory function of cells was measured by using high-resolution respirometry system Oxygraph-2k. The intracellular Ca2+ concentration was evaluated by using Fluo-4/AM and mitochondrial Ca2+ concentration by Rhod-2/AM. KEY RESULTS: The specific Piezo1 channel activator Yoda1 or its analogue Dooku1 increased [Ca2+ ]i in human umbilical vein endothelial cells (HUVECs), and both Yoda1 and Dooku1 increased mitochondrial oxygen consumption rates (OCRs) and mitochondrial ATP production in HUVECs and primary cultured rat aortic endothelial cells (RAECs). Knockdown of Piezo1 inhibited Yoda1- and Dooku1-induced increases of mitochondrial OCRs and mitochondrial ATP production in HUVECs. The shear stress mimetics, Yoda1 and Dooku1, and the Piezo1 knock-down technique also demonstrated that Piezo1 activation increased glycolysis in HUVECs. Chelating extracellular Ca2+ with EGTA or chelating cytosolic Ca2+ with BAPTA-AM did not affect Yoda1- and Dooku1-induced increases of mitochondrial OCRs and ATP production, but chelating cytosolic Ca2+ inhibited Yoda1- and Dooku1-induced increase of glycolysis. Confocal microscopy showed that Piezo1 channels are present in mitochondria of endothelial cells, and Yoda1 and Dooku1 increased mitochondrial Ca2+ in endothelial cells. CONCLUSION AND IMPLICATIONS: Piezo1 channel activation stimulates ATP production through enhancing mitochondrial respiration and glycolysis in vascular endothelial cells, suggesting a novel role of Piezo1 channel in endothelial ATP production.

Highly Strained Oxygen-Doped Chiral Molecular Belts of the Zigzag-Type with Strong Circularly Polarized Luminescence.

Herein we report a two-directional cyclization strategy for the synthesis of highly strained depth-expanded oxygen-doped chiral molecular belts of the zigzag-type. From the easily accessible resorcin[4]arenes, an unprecedented cyclization cascade generating fused 2,3-dihydro-1H-phenalenes has been developed to access expanded molecular belts. Stitching up the fjords through intramolecular nucleophilic aromatic substitution and ring-closing olefin metathesis reactions furnished a highly strained O-doped C2 -symmetric belt. The enantiomers of the acquired compounds exhibited excellent chiroptical properties. The calculated parallelly aligned electric (µ) and magnetic (m) transition dipole moments are translated to the high dissymmetry factor (|glum | up to 0.022). This study provides not only an appealing and useful strategy for the synthesis of strained molecular belts but also a new paradigm for the fabrication of belt-derived chiroptical materials with high CPL activities.

Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling.

A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world's population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood-brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.

Applying contrast-enhanced ultrasound model to distinguish atypical focal adenomyosis from uterine leiomyomas.

Background: Different from conventional ultrasound, contrast-enhanced ultrasound (CEUS) is better in observing microperfusion. For atypical focal adenomyosis and uterine leiomyomas that are difficult to be distinguished by conventional ultrasound, this study aims to further improve the differential diagnosis performance by using CEUS model. Methods: After screening the cases with difficulties in identifying focal myometrium lesions through conventional ultrasound, the number of cases covered in the focal adenomyosis group and leiomyomas group were 60 and 30 in derivation cohort, 14 and 7 in validation cohort. The qualitative and quantitative characteristics of CEUS were analyzed according to the surgical pathology. The qualitative characteristics include: the enhancement level based on the myometrium, the contrast enhancement pattern, the enhanced time of the lesion based on the myometrium, post-contrast lesion border, the distribution of the contrast agent, and the wash-out time based on the myometrium. The quantitative characteristics include: arrive time (AT), time to peak (TTP), peak intensity (PI), ΔAT, ΔTTP, ΔPI, |ΔAT|, |ΔTTP|, |ΔPI| and lesion temporal variability. Multiple logistic regression analysis was used to screen the independent risk factors, and a risk prediction model for the differential diagnosis of the two diseases was established. The area under the receiver operating characteristic (ROC) curve (AUC) was used to assess the diagnostic performance of the model. The validation cohort was used to further evaluate the diagnostic performance of the model. Results: Through the multivariate analysis, it concluded that short-term vessels first enhanced enhancement mode, unclear boundary, lesion temporal variability under CEUS >9.5 s, uneven contrast agent distribution could be independent risk factors for the diagnosis of adenomyosis [AUC =0.908, 95% confidence interval (CI): 0.833-0.982]. We also determined the sensitivity (98.33%), specificity (70.00%), positive predictive value (PPV) (86.76%), negative predictive value (NPV) (95.45%), and accuracy (87.78%) of this model. Based on pathological diagnosis, the sensitivity and specificity of the model in the validation cohort were both 85.71%, with NPV of 75% and PPV of 92.3%. The area under the ROC curve was 0.898 (95% CI: 0.742-1.000). Conclusions: The establishment of CEUS model has certain clinical application value in differentiating atypical focal adenomyosis from leiomyomas.

Adaptable Phosphate Networks towards Robust, Reprocessable, Weldable, and Alertable-Yet-Extinguishable Epoxy Vitrimer.

Covalent adaptable networks (CANs) combine the uniqueness of thermoplastics and thermosets to allow for reprocessability while being covalently crosslinked. However, it is highly desirable but rarely achieved for CANs to simultaneously demonstrate reversibility and mechanical robustness. Herein, we report a feasible strategy to develop a novel epoxy vitrimer (EV) composed of adaptable phosphate networks (APNs), by which the EVs exhibit promising mechanical properties (tensile strength of 62.5 ~ 87.8 MPa and tensile modulus of 1360.1 ~ 2975.3 MPa) under ambient conditions. At elevated temperatures, the topology rearrangement occurs relied on phosphate transesterification, which contributes to the shape memory performance, self-healing, reprocessing, and welding behaviors. Moreover, the incorporation of APNs allows for improvements in anti-ignition and also the inhibition of both heat release and smoke generation to avoid empyrosis, asphyxiation, and toxication during burning, showing expected intrinsic fire safety. Thermal, mechanical properties, and flame retardancy of the reprocessed EVs after hot pressing are very close to those of the original EVs, which is attributed to the sufficient reversibility of APNs. Accordingly, combining the aforementioned features, EVs are manufactured as flame-triggered switches for fire alarms, which symbolizes the innovative development of high-performance covalent adaptable polymeric materials.

Comparing miR-16 and miR-1228 as an optimal endogenous control for quantification of circulating microRNAs in colorectal cancer patients.

Objectives: Circulating microRNAs (miRNAs) have been discovered to play a novel role in intercellular communication and cancer biology. They are emerging candidates for noninvasive molecular biomarkers of cancer and other diseases. However, current translational researches have been limited by the lack of consensus on the optimal endogenous control of circulating miRNAs quantitation. In this study, we compared two promising miRNAs, miR-1228 and miR-16, as an endogenous control. The effects of normalizers on the relative quantification of circulating miR-31 in plasma samples of colorectal cancer (CRC) were also assessed. Materials and Methods: The cel-miR-39 was a spiked-in RNA used as an external control and added to plasma samples before RNA extraction. Quantitative real-time polymerase chain reaction technology was used to analyze the expression levels of circulating miRNAs in plasma samples of 4 healthy controls and 14 CRC patients. The expression stability of the candidate controls was compared by Ct analysis and NormFinder algorithms. Results: There was no significant difference in expression level of miR-16 and miR-1228 between healthy control group and before or after therapy of CRC patient groups. The expression of miR-1228 has smaller the range Ct values (28.25-25.64)compared with those of miR-16 (24.91-20.34). The stability value of miR-1228 (0.102) is lower than that of miR-16 (0.350). The expression of miR-1228 endogenous reference candidate has lower stability value and smaller the range Ct values compared with those in miR-16. According to the range Ct values and stability value, miR-1228 is better than miR-16 as endogenous control in CRC patients. There are significant differences in circulating miR-31 expression between healthy control and CRC patients when miR-1228 was used to standardize miR-31 expression. Conclusions: miR-1228 is recommended as a better endogenous control in quantification of circulating miRNAs in CRC patients.

High-frame-rate contrast-enhanced ultrasound findings of liver metastasis of duodenal gastrointestinal stromal tumor: A case report and literature review.

BACKGROUND: Liver metastasis of duodenal gastrointestinal stromal tumor (GIST) is rare. Most reports mainly focus on its treatment and approaches to surgical resection, while details on its contrast-enhanced ultrasound (CEUS) findings are lacking. The diagnosis and imaging modalities for this condition remain challenging. CASE SUMMARY: A 53-year-old Chinese man presented with mild signs and symptoms of the digestive tract. He underwent routine examinations after GIST surgery. Magnetic resonance imaging showed a 2.3 cm hepatic space-occupying lesion. All the laboratory test results were within normal limits. For further diagnostic confirmation, we conducted high frame rate CEUS (H-CEUS) and found a malignant perfusion pattern. Heterogeneous concentric hyper-enhancement, earlier wash-in than the liver parenchyma, and two irregular vessel columns could be observed at the periphery of the lesion during the arterial phase. Ultrasound-guided puncture biopsy was used to confirm the diagnosis of the lesion as liver metastasis of duodenal GIST. Imatinib was prescribed after biopsy, and the patient's clinical course was monitored. CONCLUSION: H-CEUS is useful for detecting microcirculation differences, wash-in patterns, and vascular morphogenesis and diagnosing liver metastasis of duodenal GIST.

Biometric and Structural Ocular Manifestations of Anterior Megalophthalmos.

Objective: The aim of this study was to examine the biometric ocular manifestations and structural ocular features of anterior megalophthalmos (AM). Methods: Fifteen patients with AM (30 eyes) from the Eye & ENT Hospital of Fudan University were included. The age-matched control group consisted of 30 participants (30 eyes) who underwent Pentacam HR and IOLMaster 700 measurements for one normal eye. Data on demographics, biometric manifestations, and genotypes were carefully compared. Results: A total of 15 patients with AM and 30 control patients were enrolled. There were no differences in age (37.27 ± 19.1 vs. 31.43 ± 19.69 years, P = 0.249) between these two groups. AM eyes were characterized by premature cataracts (11/30, 36.67%) and zonular weakness with lens subluxation (22/30, 73.33%) compared with the control group. Notably, 20 of the 30 AM eyes (66.67%) had significant posterior iris bowing, and 16 of the 30 AM eyes (53.33%) showed an enlarged ciliary ring on ultrasound biomicroscopy (UBM). Mean corneal curvature was lower in the AM eyes (42.01 ± 2.06 D vs. 43.14 ± 1.38 D, P = 0.023). There was no significant difference in corneal pachymetry and central endothelial cell count between the AM and control groups. Significant differences were found in terms of the anterior chamber and white-to-white (WTW) among the Pentacam HR and IOLMaster 700 in patients with AM (P < 0.05). The difference was 0.53 ± 0.48 mm and 0.36 ± 0.14 mm, respectively (P < 0.001). Conclusion: The results of this cohort study conclude the biometric and structural ocular manifestations in Chinese cohorts. Posterior iris bowing (66.67%) and lens subluxation (73.33%) are the most characteristic findings in patients with AM with anatomical abnormalities of megalocornea and a deep anterior chamber, although corneal biometric manifestations of AM included flatter cornea and lower total corneal astigmatism. The knowledge of ocular manifestations of AM is important for diagnosis and preparation for the operation in advance to avoid intraoperative and postoperative complications. Significant differences were found in the anterior chamber and WTW values between the Pentacam HR and IOLMaster 700. Thus, we suggest that various examinations should be carefully considered before determining an AM diagnosis.