A prefrontal-habenular circuitry regulates social fear behaviour.

The medial prefrontal cortex (mPFC) has been implicated in the pathophysiology of social impairments including social fear. However, the precise subcortical partners that mediate mPFC dysfunction on social fear behaviour have not been identified. Employing a social fear conditioning paradigm, we induced robust social fear in mice and found that the lateral habenula (LHb) neurons and LHb-projecting mPFC neurons are synchronously activated during social fear expression. Moreover, optogenetic inhibition of the mPFC-LHb projection significantly reduced social fear responses. Importantly, consistent with animal studies, we observed an elevated prefrontal-habenular functional connectivity in subclinical individuals with higher social anxiety characterized by heightened social fear. These results unravel a crucial role of the prefrontal-habenular circuitry in social fear regulation and suggest that this pathway could serve as a potential target for the treatment of social fear symptom often observed in many psychiatric disorders.

Oblique impingement of binary droplets at the nanoscale on superhydrophobic surfaces: A molecular dynamics study.

The impacting phenomenon of nanodroplets has received much attention due to their importance in various industrial applications. The oblique impingement of single droplets is well understood; however, the effect of oblique angle on impacting the dynamics of multiple droplets at the nanoscale is very limited. To address this gap, we perform molecular dynamics (MD) simulations to study the impacting dynamics of binary nanodroplets with various oblique angles (αob) and Weber numbers (We). Using MD simulations, we directly capture the detailed morphological evolution of the impacting binary droplets with various given conditions. Compared to the oblique impingement of a single droplet, the evolution of impacting binary droplets involves two novel dynamic characteristics: the asymmetric dynamics with droplet preferential spreading in the y direction and the rotating of the coalescing droplet. The mechanisms underlying are well studied. The asymmetric dynamics is a result of the velocity gradient of the outer edge of the spreading droplet, and the rotating effect is due to the change in angular momentum induced by surface force. The analysis and study of these phenomena have never been mentioned in previous studies of single droplet. Finally, we investigate the effect of αob and We on normalized moving distance (L/Dsin) and contact time (tc). This work paves the way for offering a comprehensive understanding of the oblique impingement of binary nanodroplets.

Serum LINC00339 is a promising biomarker for prognosis prediction of nasopharyngeal carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) in serum were useful and promising biomarkers for diagnostic and prognostic application. Herein, we investigated the serum lncRNA LINC00339 expression and its role in nasopharyngeal carcinoma. METHODS: In this study, we recruited a cohort of 129 nasopharyngeal carcinoma patients, 68 patients with nasopharyngitis, and 80 healthy controls. Serum LINC00339 levels were measured by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic (ROC) and Kaplan-Meier curve analyses were conducted to evaluate th e clinical role of LINC00339. The effects of linc00339 on cellular activities were measured using CCK-8 and Transwell assays. RESULTS: We observed that serum LINC00339 expression was upregulated in nasopharyngeal carcinoma patients and closely associated with tumor node metastasis stage, lymph node metastasis, and overall survival rate. Meanwhile, ROC analysis showed serum LINC00339 had diagnostic value to distinguish nasopharyngeal carcinoma patients from healthy individuals and nasopharyngitis patients. Silencing of LINC00339 could repress cellular behaviors by targeting miR-152. CONCLUSION: This study clarified that LINC00339 was upregulated in nasopharyngeal carcinoma, and that serum LINC00339 may act as a diagnostic or prognostic marker, and a hopeful therapeutic target for patients with nasopharyngeal carcinoma.

Fus3 Interacts with Gal83, Revealing the MAPK Crosstalk to Snf1/AMPK to Regulate Secondary Metabolic Substrates in Aspergillus flavus.

Aflatoxins (AFs), highly carcinogenic natural products, are produced by the secondary metabolism of fungi such as Aspergillus flavus. Essential for the fungi to respond to environmental changes and aflatoxin synthesis, the pheromone mitogen-activated protein kinase (MAPK) is a potential regulator of aflatoxin biosynthesis. However, the mechanism by which pheromone MAPK regulates aflatoxin biosynthesis is not clear. Here, we showed Gal83, a new target of Fus3, and identified the pheromone Fus3-MAPK signaling pathway as a regulator of the Snf1/AMPK energy-sensing pathway modulating aflatoxins synthesis substrates. The screening for Fus3 target proteins identified the ß subunit of Snf1/AMPK complexes using tandem affinity purification and multiomics. This subunit physically interacted with Fus3 both in vivo and in vitro and received phosphorylation from Fus3. Although the transcript levels of aflatoxin synthesis genes were not noticeably downregulated in both gal83 and fus3 deletion mutant strains, the levels of aflatoxin B1 and its synthesis substrates and gene expression levels of primary metabolizing enzymes were significantly reduced. This suggests that both the Fus3-MAPK and Snf1/AMPK pathways respond to energy signals. In conclusion, all the evidence unlocks a novel pathway of Fus3-MAPK to regulate AFs synthesis substrates by cross-talking with the Snf1/AMPK complexes.

Analysis of the impact of drying on common wheat quality and safety.

Mycotoxin contamination in grain has been an ongoing concern in the world. Wheat, as a staple crop in China, is particularly notable for its mycotoxin contamination. The main mycotoxins in wheat include deoxynivalenol (DON) and its derivates, zearalenone (ZEN) and aflatoxin B1 (AFB1). After harvest, drying process is an effective technique and a necessary step to ensure the long-term safe storage of wheat. In this study, the moisture content, the concentrations of total fungi and main mycotoxins in post-harvest wheat of three wheat growing areas in the North China Plain were examined, and the effect of different drying methods on wheat quality was evaluated. The results showed that 87.5% of wheat samples were simultaneously contaminated with two or more mycotoxins. Due to the pre-harvest heavy rainfall, the moisture content, the levels of total fungi and mycotoxins in wheat samples of Liaocheng city were significantly higher compared to other regions. Moreover, the effects of different drying methods on the starch gelatinization and viscosity properties of wheat were investigated. The results showed that both natural air drying and dryer drying altered the crystal structure within starch particles and affected the gelatinization and viscosity properties of wheat starch. However, there is no significant difference between the wheat samples treated with two drying methods.

Real-world experience of thrombopoietin receptor agonists in pediatric immune thrombocytopenia: a report from a Chinese tertiary children's hospital.

Background: Primary immune thrombocytopenia (ITP) is the most common bleeding disorder in children. There are approximately 20% pediatric ITP patients respond poor to corticosteroids as first-line treatment. Recently thrombopoietin receptor agonists (TPO-RAs) have been used to treat refractory ITP and have achieved certain therapeutic effects. To investigate the efficacy and safety of TPO-RAs in the treatment of pediatric ITP, we conducted this real-world study. Methods: Fifty-three pediatric patients with ITP who did not respond well to corticosteroids were treated with TPO-RAs. Clinical data, including therapeutic response rate, changes in platelet (PLT) count, and adverse events (AEs) were collected. Results: Of the 51 evaluable patients, 37 (72.5%) responded to TPO-RAs. Patients aged >4 years had a higher response rate than those aged ≤4 years (81.1% vs. 50.0%, P=0.04). There was no effect of sex, duration of disease, prior therapy, Mycoplasma pneumoniae (MP) immunoglobulin M (IgM) positivity, antinuclear antibody (ANA) positivity, CD4/CD8 ratio or baseline PLT count on the response rate (P>0.05). Other than 10 patients with PLT counts that exceeded the upper limit of normal, AEs were sporadic, including increased aminotransferase levels, cough, headache, and vomiting. Conclusions: TPO-RAs exhibited good clinical efficacy in pediatric ITP patients who failed to respond to first-line treatment, especially patients aged >4 years, and the side effects were minor.

Cardiologist-level interpretable knowledge-fused deep neural network for automatic arrhythmia diagnosis.

BACKGROUND: Long-term monitoring of Electrocardiogram (ECG) recordings is crucial to diagnose arrhythmias. Clinicians can find it challenging to diagnose arrhythmias, and this is a particular issue in more remote and underdeveloped areas. The development of digital ECG and AI methods could assist clinicians who need to diagnose arrhythmias outside of the hospital setting. METHODS: We constructed a large-scale Chinese ECG benchmark dataset using data from 272,753 patients collected from January 2017 to December 2021. The dataset contains ECG recordings from all common arrhythmias present in the Chinese population. Several experienced cardiologists from Shanghai First People's Hospital labeled the dataset. We then developed a deep learning-based multi-label interpretable diagnostic model from the ECG recordings. We utilized Accuracy, F1 score and AUC-ROC to compare the performance of our model with that of the cardiologists, as well as with six comparison models, using testing and hidden data sets. RESULTS: The results show that our approach achieves an F1 score of 83.51%, an average AUC ROC score of 0.977, and 93.74% mean accuracy for 6 common arrhythmias. Results from the hidden dataset demonstrate the performance of our approach exceeds that of cardiologists. Our approach also highlights the diagnostic process. CONCLUSIONS: Our diagnosis system has superior diagnostic performance over that of clinicians. It also has the potential to help clinicians rapidly identify abnormal regions on ECG recordings, thus improving efficiency and accuracy of clinical ECG diagnosis in China. This approach could therefore potentially improve the productivity of out-of-hospital ECG diagnosis and provides a promising prospect for telemedicine.

Arrhythmia, also known as an irregular heartbeat, is a common cardiovascular disease. Sometimes the presence of an arrhythmia can increase the risk of more serious heart conditions. Long-term monitoring of the heartbeat enables arrhythmia to be more easily diagnosed. To accurately detect arrhythmia, we developed a computational model that was able to detect six common types of arrhythmias from readings of the heart rate obtained using a device connected to a mobile phone. We showed that our model could diagnose these arrhythmias in over 270,000 people living in China. Our diagnostic system could enable arrhythmias to be diagnosed more easily outside of hospitals and therefore improve access to healthcare, particularly for those in remote settings.

MiR-3682-3p promotes esophageal cancer progression by targeting FHL1 and activating the Wnt/ß-catenin signaling pathway.

BACKGROUND: Esophageal cancer (EC) is highly ranked among all cancers in terms of its incidence and mortality rates. MicroRNAs (miRNAs) are considered to play key regulatory parts in EC. Multiple research studies have indicated the involvement of miR-3682-3p and four and a half LIM domain protein 1 (FHL1) in the achievement of tumors. The aim of this research was to clarify the significance of these genes and their possible molecular mechanism in EC. METHODS: Data from a database and the tissue microarray were made to analyze the expression and clinical significance of miR-3682-3p or FHL1 in EC. Reverse transcription quantitative PCR and Western blotting were used to detect the expression levels of miR-3682-3p and FHL1 in EC cells. CCK8, EdU, wound healing, Transwell, flow cytometry, and Western blotting assays were performed to ascertain the biological roles of miR-3682-3p and FHL1 in EC cells. To confirm the impact of miR-3682-3p in vivo, a subcutaneous tumor model was created in nude mice. The direct interaction between miR-3682-3p and FHL1 was demonstrated through a luciferase assay, and the western blotting technique was employed to assess the levels of crucial proteins within the Wnt/ß-catenin pathway. RESULTS: The noticeable increase in the expression of miR-3682-3p and the decrease in the expression of FHL1 were observed, which correlated with a negative impact on the patients' overall survival. Upregulation of miR-3682-3p expression promoted the growth and metastasis of EC, while overexpression of FHL1 partially reversed these effects. Finally, miR-3682-3p motivates the Wnt/ß-catenin signal transduction by directly targeting FHL1. CONCLUSION: MiR-3682-3p along the FHL1 axis activated the Wnt/ß-catenin signaling pathway and thus promoted EC malignancy.

A highly efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for etomidate and etomidate acid in urine, liver and kidney.

Etomidate (ETO) is a highly-efficient drug that can induce anesthesia with increasing doses, thus subject to strict regulation. However, an accurate and efficient method for ETO intake detection is currently lacking. Therefore, this study developed a straightforward sample preparation method using LC-MS/MS to analyze ETO and its primary metabolite, etomidate acid (ETA), in urine, liver, and kidney samples. Snap frozen pig liver and kidney samples were ground into a fine powder. Then, all the biological samples, including human urine, pig liver and kidney tissues, were deproteinized using acetonitrile and filtered for analysis. The separation was achieved in 9.01 min with gradient elution. The calibration curves ranged from 0.5 to 50 ng/mL for ETO in urine and 0.5 to 50 ng/g in liver and kidney, while the curves ranged from 1 to 100 ng/mL for ETA in urine and 1 to 100 ng/g in liver and kidney. The correlation coefficients (R2) were greater than 0.9957. The Limit of detection (LOD) and limit of quantitation (LOQ) for ETO were 0.2 and 0.5 ng/mL in urine samples and 0.2 and 0.5 ng/g in liver and kidney samples, respectively. For ETA, the LOD and LOQ were 0.5 and 1 ng/mL in urine samples and 0.5 and 1 ng/g in liver and kidney samples. This method was assessed by validation parameters, including selectivity, intra- and inter-day precision and accuracy, recovery, matrix effect, dilution integrity and stability. It was successfully applied to a practical case, revealing ETO and ETA concentrations in urine of 1.01 and 5.58 µg/mL, in liver samples of 12.30 and 1.13 µg/g, and in kidney samples of 6.95 and 4.23 µg/g. This suggests that the method is suitable for routine forensic detection of illicit ETO abuse.

In Situ Unveiling of the Resistive Switching Mechanism of Halide Perovskite-Based Memristors.

The organic-inorganic halide perovskite has become one of the most promising candidates for next-generation memory devices, i.e. memristors, with excellent performance and solution-processable preparation. Yet, the mechanism of resistive switching in perovskite-based memristors remains ambiguous due to a lack of in situ visualized characterization methods. Here, we directly observe the switching process of perovskite memristors with in situ photoluminescence (PL) imaging microscopy under an external electric field. Furthermore, the corresponding element composition of conductive filaments (CFs) is studied, indicating that the metallic CFs with respect to the activity of the top electrode are essential for device performance. Finally, electrochemical impedance spectroscopy (EIS) is conducted to reveal that the transition of ion states is associated with the formation of metallic CFs. This study provides in-depth insights into the switching mechanism of perovskite memristors, paving a pathway to develop and optimize high-performance perovskite memristors for large-scale applications.

Validation of the "obturator functioning scale" for Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy.

Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.

Identification of a novel B-cell epitope of the African swine fever virus p34 protein and development of an indirect ELISA for the detection of serum antibodies.

African swine fever (ASF) is a viral disease caused by the African swine fever virus that can be highly transmitted and lethal in domestic pigs. In the absence of a vaccine, effective diagnosis is critical for minimizing the virus's spread. In recent years, with the decline of African swine fever virus (ASFV) virulence, antibody detection has become an important means of detection. ASFV nucleocapsid protein p34 is a mature hydrolytic product of pp220, which is highly conserved and has a high content in the structural protein of the virus. Prokaryotic cells were chosen to generate highly active and high-yield p34 protein, which was then used as an antigen for producing mouse monoclonal antibodies. The B-cell epitope 202QKELDKLQT210, which was highly conserved and found on the surface of the p34 protein, was first identified by an anti-p34 monoclonal antibody utilizing the peptide scanning technique and visualized in helix. This supported the viability of p34 protein detection even further. In addition, we established an indirect ELISA assay based on p34 to detect ASFV antibodies. The coincidence rate of this method with commercially available kits was shown to be 97.83%. Sensitivity analysis revealed that it could be detected in serum dilution as low as 1:6400, and there was no cross-reaction with other prevalent porcine epidemic diseases classical swine fever virus (CSFV), foot-and-mouth disease virus (FMDV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine circovirus 2 (PCV2). In summary, the established ELISA method and anti-P34 monoclonal antibody have demonstrated that the p34 protein has a promising application prospect for the detection of African swine fever antibodies.