Electrical Control of Uniformity in Quantum Dot Devices.

Highly uniform quantum systems are essential for the practical implementation of scalable quantum processors. While quantum dot spin qubits based on semiconductor technology are a promising platform for large-scale quantum computing, their small size makes them particularly sensitive to their local environment. Here, we present a method to electrically obtain a high degree of uniformity in the intrinsic potential landscape using hysteretic shifts of the gate voltage characteristics. We demonstrate the tuning of pinch-off voltages in quantum dot devices over hundreds of millivolts that then remain stable at least for hours. Applying our method, we homogenize the pinch-off voltages of the plunger gates in a linear array for four quantum dots, reducing the spread in pinch-off voltages by one order of magnitude. This work provides a new tool for the tuning of quantum dot devices and offers new perspectives for the implementation of scalable spin qubit arrays.

circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma.

Emerging evidence has demonstrated that circular RNAs (circRNA) are involved in cancer metastasis. Further elucidation of the role of circRNAs in oral squamous cell carcinoma (OSCC) could provide insights into mechanisms driving metastasis and potential therapeutic targets. Here, we identify a circRNA, circFNDC3B, that is significantly upregulated in OSCC and is positively associated with lymph node (LN) metastasis. In vitro and in vivo functional assays showed that circFNDC3B accelerated the migration and invasion of OSCC cells and the tube-forming capacity of human umbilical vein endothelial cells and human lymphatic endothelial cells. Mechanistically, circFNDC3B regulated ubiquitylation of the RNA-binding protein FUS and the deubiquitylation of HIF1A through the E3 ligase MDM2 to promote VEGFA transcription, thereby enhancing angiogenesis. Meanwhile, circFNDC3B sequestered miR-181c-5p to upregulate SERPINE1 and PROX1, which drove epithelial-mesenchymal transition (EMT) or partial-EMT (p-EMT) in OSCC cells and promoted lymphangiogenesis to accelerate LN metastasis. Overall, these findings uncovered the mechanistic role of circFNDC3B in orchestrating cancer cell metastatic properties and vasculature formation, suggesting circFNDC3B could be a potential target to reduce OSCC metastasis. SIGNIFICANCE: Dual functions of circFNDC3B in enhancing the metastatic ability of cancer cells and promoting vasculature formation through regulation of multiple pro-oncogenic signaling pathways drive lymph node metastasis of OSCC.

Panic Attack Prediction Using Wearable Devices and Machine Learning: Development and Cohort Study.

BACKGROUND: A panic attack (PA) is an intense form of anxiety accompanied by multiple somatic presentations, leading to frequent emergency department visits and impairing the quality of life. A prediction model for PAs could help clinicians and patients monitor, control, and carry out early intervention for recurrent PAs, enabling more personalized treatment for panic disorder (PD). OBJECTIVE: This study aims to provide a 7-day PA prediction model and determine the relationship between a future PA and various features, including physiological factors, anxiety and depressive factors, and the air quality index (AQI). METHODS: We enrolled 59 participants with PD (Diagnostic and Statistical Manual of Mental Disorders, 5th edition, and the Mini International Neuropsychiatric Interview). Participants used smartwatches (Garmin Vívosmart 4) and mobile apps to collect their sleep, heart rate (HR), activity level, anxiety, and depression scores (Beck Depression Inventory [BDI], Beck Anxiety Inventory [BAI], State-Trait Anxiety Inventory state anxiety [STAI-S], State-Trait Anxiety Inventory trait anxiety [STAI-T], and Panic Disorder Severity Scale Self-Report) in their real life for a duration of 1 year. We also included AQIs from open data. To analyze these data, our team used 6 machine learning methods: random forests, decision trees, linear discriminant analysis, adaptive boosting, extreme gradient boosting, and regularized greedy forests. RESULTS: For 7-day PA predictions, the random forest produced the best prediction rate. Overall, the accuracy of the test set was 67.4%-81.3% for different machine learning algorithms. The most critical variables in the model were questionnaire and physiological features, such as the BAI, BDI, STAI, MINI, average HR, resting HR, and deep sleep duration. CONCLUSIONS: It is possible to predict PAs using a combination of data from questionnaires and physiological and environmental data.

Identification of the canonical and noncanonical role of miR-143/145 in estrogen-deficient bone loss.

Rationale: Postmenopausal-induced bone loss is mainly caused by declining core transcription factors (TFs) of bone mesenchymal stem cells (BMSCs), but little is known about how miRNAs regulate chromatin structure remodeling of TFs gene to maintain BMSCs function in bone homeostasis. Methods: We examined the serum, salivary and bone samples from Pre- and Post-menopause women by paired analysis and confirmed canonical ceRNA role of MIR143HG and miR-143/145 complexes in cytoplasm and noncanonical role for SOX2 transcription in nucleus (FISH, qRT-PCR, immunostaining, Luciferase assays and ChIP). Moreover, we took advantage of transgenic mice under OVX-induced osteoporosis, studying the in vitro and in vivo effect of miR-143/145 deletion on BMSCs function and bone homeostasis. Last, using miRNA antagonism, antagomiR-143/145 were delivered into bone marrow to treat estrogen-deficient bone loss. Results: Here, we identified miR-143/145 as potential diagnostic candidates for postmenopausal osteoporosis, and miR-143/145 overexpression impaired BMSCs self-renewing and differentiation function. Mechanistically, we confirmed that cytoplasmic miR-143/145 and LncRNA MIR143HG, that controlled by ERß, cooperatively regulated pluripotency genes translation via canonical ceRNA pathway, and MIR143HG cooperates with miR­143 to nuclear translocation for co-activation of SOX2 transcription via opening promoter chromatin. Meanwhile, miR­143/145 were shuttled into osteoclasts in extracellular vesicles and triggered osteoclastic activity by targeting Cd226 and Srgap2. Furthermore, miR-143/145-/- mice or using chemically­modified antagomiR-143/145 significantly alleviated estrogen-deficient osteoporosis. Conclusions: Our findings reveal a canonical and noncanonical role of miR-143/145 in controlling BMSCs pluripotency and unfold their dual effect on bone formation and bone resorption, suggesting miR-143/145 as promising therapeutic targets for treating estrogen-deficient bone loss.

Blood and Salivary MicroRNAs for Diagnosis of Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

PURPOSE: This meta-analysis aimed to compare and evaluate the diagnostic accuracy of blood and salivary microRNAs (miRNAs) in discriminating oral squamous cell carcinoma (OSCC). METHODS: The PubMed, Embase, Web of Science, and Cochrane Library were searched (updated to February 2020) to identify all articles describing the diagnostic value of blood and salivary miRNAs for OSCC. The pooled parameters were calculated using Revman (v.5.3) and STATA (v.14.0). RESULTS: Twenty articles involving 1,106 patients and 732 controls were included in this meta-analysis. The pooled sensitivity and specificity of salivary miRNAs were 0.70 (95% CI: 0.63-0.77) and 0.82 (95% CI: 0.72-0.90). For blood miRNAs, they were 0.79 (95% CI: 0.73-0.84) and 0.82 (95% CI: 0.77-0.86). The areas under receiver operating characteristic curve in saliva, blood, and body fluid miRNAs were 0.80 (95% CI: 0.77-0.84), 0.88 (95% CI: 0.84-0.90), and 0.87 (95% CI: 0.84-0.90), respectively. CONCLUSIONS: The results of this meta-analysis indicate a moderate diagnostic accuracy of blood and salivary miRNAs presented for OSCC. These findings may provide less invasive and relatively reliable diagnostic tools for OSCC detection.