Asymmetric bulges within hairpin RNA transgenes influence small RNA size, secondary siRNA production and viral defence.

Small RNAs (sRNAs) are essential for normal plant development and range in size classes of 21-24 nucleotides. The 22nt small interfering RNAs (siRNAs) and miRNAs are processed by Dicer-like 2 (DCL2) and DCL1 respectively and can initiate secondary siRNA production from the target transcript. 22nt siRNAs are under-represented due to competition between DCL2 and DCL4, while only a small number of 22nt miRNAs exist. Here we produce abundant 22nt siRNAs and other siRNA size classes using long hairpin RNA (hpRNA) transgenes. By introducing asymmetric bulges into the antisense strand of hpRNA, we shifted the dominant siRNA size class from 21nt of the traditional hpRNA to 22, 23 and 24nt of the asymmetric hpRNAs. The asymmetric hpRNAs effectively silenced a ß-glucuronidase (GUS) reporter transgene and the endogenous ethylene insensitive-2 (EIN2) and chalcone synthase (CHS) genes. Furthermore, plants containing the asymmetric hpRNA transgenes showed increased amounts of 21nt siRNAs downstream of the hpRNA target site compared to plants with the traditional hpRNA transgenes. This indicates that these asymmetric hpRNAs are more effective at inducing secondary siRNA production to amplify silencing signals. The 22nt asymmetric hpRNA constructs enhanced virus resistance in plants compared to the traditional hpRNA constructs.

G-U base-paired hpRNA confers potent inhibition of small RNA function in plants.

MicroRNA (miRNA) target mimicry technologies, utilizing naturally occurring miRNA decoy molecules, represent a potent tool for analyzing miRNA function. In this study, we present a highly efficient small RNA (sRNA) target mimicry design based on G-U base-paired hairpin RNA (hpG:U), which allows for the simultaneous targeting of multiple sRNAs. The hpG:U constructs consistently generate high amounts of intact, polyadenylated stem-loop (SL) RNA outside the nuclei, in contrast to traditional hairpin RNA designs with canonical base pairing (hpWT), which were predominantly processed resulting in a loop. By incorporating a 460-bp G-U base-paired double-stranded stem and a 312-576 nt loop carrying multiple miRNA target mimicry sites (GUMIC), the hpG:U construct displayed effective repression of three Arabidopsis miRNAs, namely miR165/166, miR157, and miR160, both individually and in combination. Additionally, a GUMIC construct targeting a prominent cluster of siRNAs derived from cucumber mosaic virus (CMV) Y-satellite RNA (Y-Sat) effectively inhibited Y-Sat siRNA-directed silencing of the chlorophyll biosynthetic gene CHLI, thereby reducing the yellowing symptoms in infected Nicotiana plants. Therefore, the G-U base-paired hpRNA, characterized by differential processing compared to traditional hpRNA, acts as an efficient decoy for both miRNAs and siRNAs. This technology holds great potential for sRNA functional analysis and the management of sRNA-mediated diseases.

Cervical lymph node metastasis prediction from papillary thyroid carcinoma US videos: a prospective multicenter study.

BACKGROUND: Prediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance. METHODS: From September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model. From January 2019 to July 2021, PTC patients from four different centers were prospectively enrolled to fine-tune and independently validate MMD-DL. Its diagnostic performance and auxiliary effect on radiologists were analyzed in terms of receiver operating characteristic (ROC) curves, areas under the ROC curve (AUC), accuracy, sensitivity, and specificity. RESULTS: In total, 488 PTC patients were enrolled in the pre-training cohort, and 218 PTC patients were included for model fine-tuning (n = 109), internal test (n = 39), and external validation (n = 70). Diagnostic performances of MMD-DL achieved AUCs of 0.85 (95% CI: 0.73, 0.97) and 0.81 (95% CI: 0.73, 0.89) in the test and validation cohorts, respectively, and US radiologists significantly improved their average diagnostic accuracy (57% vs. 60%, P = 0.001) and sensitivity (62% vs. 65%, P < 0.001) by using the AI model for assistance. CONCLUSIONS: The AI model using US videos can provide accurate and reproducible prediction of cervical lymph node metastasis in papillary thyroid carcinoma patients preoperatively, and it can be used as an effective assisting tool to improve diagnostic performance of US radiologists. TRIAL REGISTRATION: We registered on the Chinese Clinical Trial Registry website with the number ChiCTR1900025592.

Magnetic Resonance Imaging-Based Classification Systems for Informing Better Outcomes of Adenomyosis After Ultrasound-Guided High-Intensity Focused Ultrasound Ablating Surgery.

BACKGROUND: A referenced MRI-based classification associated with focused ultrasound ablation surgery (FUAS) outcomes is lacking in adenomyosis. PURPOSE: To identify an MRI-based classification system for informing the FUAS outcomes. STUDY TYPE: Retrospective. POPULATION: Patients with FUAS for adenomyosis, were divided into a training set (N = 643; 355 with post-FUAS gonadotropin-releasing hormone/levonorgestrel, 288 without post-FUAS therapy) and an external validation set (N = 135; all without post-FUAS therapy). FIELD STRENGTH/SEQUENCE: 1.5 T, turbo spin-echo T2-weighted imaging and single-shot echo-planar diffusion-weighted imaging sequences. ASSESSMENT: Five MRI-based adenomyosis classifications: classification 1 (C1) (diffuse, focal, and mild), C2 (intrinsic, extrinsic, intramural, and indeterminate), C3 (internal, adenomyomas, and external), C4 (six subtypes on areas [internal or external] and volumes [<1/3 or ≥2/3]), and C5 (internal [asymmetric or symmetric], external, intramural, full thickness [asymmetric or symmetric]) for FUAS outcomes (symptom relief and recurrence). STATISTICAL TESTS: The optimal classification was significantly associated with the most subtypes of FUAS outcomes. Relating to the timing of recurrence was measured using Cox regression analysis and median recurrence time was estimated by a Kaplan-Meier curve. A P value <0.05 was considered statistically significant. RESULTS: Dysmenorrhea relief and recurrence were only associated with C2 in training patients undergoing FUAS alone. Compared with other subtypes, the extrinsic subtype of C2 was significantly associated with dysmenorrhea recurrence in the FUAS group. Besides, the median dysmenorrhea recurrence time of extrinsic subtype was significantly shorter than that of other subtypes (42.0 months vs. 50.3 months). In the validation cohort, C2 was confirmed as the optimal system and its extrinsic subtype was confirmed to have a significantly shorter dysmenorrhea recurrence time than other subtypes. DATA CONCLUSION: Classification 2 can inform dysmenorrhea relief and recurrence in patients with adenomyosis undergoing FAUS only. Itsextrinsic subtype was associated with an earlier onset of dysmenorrhea recurrence after treatment. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Insight into the Feasibility of Fatty Acyl Chlorides with 10-18 Carbons for the Ball-Milling Synthesis of Thermoplastic Cellulose Esters.

Fatty acid cellulose esters (FACE) are common cellulose-based thermoplastics, and their thermoplasticity is determined by both the contents and the lengths of the side chains. Herein, various FACE were synthesized by the ball-milling esterification of cellulose and fatty acyl chlorides containing 10-18 carbons, and their structures and thermoplasticity were thoroughly studied. The results showed that FACE with high degrees of substitution (DS) and low melting flow temperatures (Tf) were achieved as the chain lengths of the fatty acyl chlorides were reduced. In particular, a cellulose decanoate with a DS of 1.85 and a Tf of 186 °C was achieved by feeding 3 mol of decanoyl chloride per mole anhydroglucose units of cellulose. However, cellulose stearate (DS = 1.53) synthesized by the same protocols cannot melt even at 250 °C. More interestingly, the fatty acyl chlorides with 10 and 12 carbons resulted in FACE with superior toughness (elongation at break up to 94.4%). In contrast, due to their potential crystallization of the fatty acyl groups with 14-18 carbons, the corresponding FACE showed higher tensile strength and Young's modulus than the others. This study provides some theoretical basis for the mechanochemical synthesis of thermoplastic FACE with designated properties.

Improved Patient Adherence to Family-Based Helicobacter pylori Infection Control and Management Strategy in Central China and Its Influencing Factors.

BACKGROUND: Patient adherence status to the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management strategy remains unclear, so are its influencing factors. We aim to investigate family members' adherence and its influencing factors during the family-based H. pylori infection management practice for related disease prevention. MATERIALS AND METHODS: Based on our previously family-based H. pylori survey in 2021, 282 families including 772 individuals were followed up 2 years after the initial survey to compare if the investigation and education might improve family member's adherence. The participant's adherence to H. pylori infection awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were followed up, and their influencing factors were also analyzed. RESULTS: The overall participant's adherence to recommendations on H. pylori awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were 77% (187/243), 67.3% (138/205), 60.1% (211/351), 46.5% (107/230), 45.6% (159/349), and 39.1% (213/545), respectively; and all showed improvements compared with their prior survey stages. The top reasons for rejection to treatment, retest, and gastroscopy were forgetting or unaware of H. pylori infection (30.3%), busy (32.8%), and asymptomatic (67.9%), respectively. Independent risk factor for low adherence to treatment was occupation (e.g., staff: OR 4.49, 95% CI 1.34-15.10). Independent favorable factors for treatment adherence were individuals at the ages of 18-44 years (OR 0.19, 95% CI 0.04-0.89) and had a large family size (e.g., four family members: OR 0.15, 95% CI 0.06-0.41); for retest adherence, it was individuals at the ages of 60-69 years (OR 0.23, 95% CI 0.06-0.97); for gastroscopy adherence, it was individuals at the age of 60-69 years (OR 0.46, 95% CI 0.28-0.75), and with gastrointestinal symptoms (OR 0.57, 95% CI 0.36-0.90). CONCLUSIONS: Family-based H. pylori management increases individual adherence to treatment, retest, and awareness, and there are also improved adherence to gastroscopy, publicity, and personal hygiene recommendations; further efforts are required to enhance the individual adherence rate for related disease prevention.

Effects of meteorological factors on influenza transmissibility by virus type/subtype.

BACKGROUND: Quantitative evidence on the impact of meteorological factors on influenza transmissibility across different virus types/subtypes is scarce, and no previous studies have reported the effect of hourly temperature variability (HTV) on influenza transmissibility. Herein, we explored the associations between meteorological factors and influenza transmissibility according to the influenza type and subtype in Guangzhou, a subtropical city in China. METHODS: We collected influenza surveillance and meteorological data of Guangzhou between October 2010 and December 2019. Influenza transmissibility was measured using the instantaneous effective reproductive number (Rt). A gamma regression with a log link combined with a distributed lag non-linear model was used to assess the associations of daily meteorological factors with Rt by influenza types/subtypes. RESULTS: The exposure-response relationship between ambient temperature and Rt was non-linear, with elevated transmissibility at low and high temperatures. Influenza transmissibility increased as HTV increased when HTV < around 4.5 °C. A non-linear association was observed between absolute humidity and Rt, with increased transmissibility at low absolute humidity and at around 19 g/m3. Relative humidity had a U-shaped association with influenza transmissibility. The associations between meteorological factors and influenza transmissibility varied according to the influenza type and subtype: elevated transmissibility was observed at high ambient temperatures for influenza A(H3N2), but not for influenza A(H1N1)pdm09; transmissibility of influenza A(H1N1)pdm09 increased as HTV increased when HTV < around 4.5 °C, but the transmissibility decreased with HTV when HTV < 2.5 °C and 3.0 °C for influenza A(H3N2) and B, respectively; positive association of Rt with absolute humidity was witnessed for influenza A(H3N2) even when absolute humidity was larger than 19 g/m3, which was different from that for influenza A(H1N1)pdm09 and influenza B. CONCLUSIONS: Temperature variability has an impact on influenza transmissibility. Ambient temperature, temperature variability, and humidity influence the transmissibility of different influenza types/subtypes discrepantly. Our findings have important implications for improving preparedness for influenza epidemics, especially under climate change conditions.

Magnetic resonance imaging-based Classifications for Symptom of Adenomyosis.

OBJECTIVES: To identify an optimal magnetic resonance imaging (MRI)-based classification for the severity of adenomyosis and explore the factors associated with disease severity (dysmenorrhea or menorrhagia). DESIGN AND PARTICIPANTS: Several classifications based on MRI have been proposed, and their phenotypes are reported to be associated with the severity of adenomyosis. However, a consensus classification based on MRI findings has not yet been reached. Our study was designed to retrospectively analyze data from a cohort of patients in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to December 2021 before focused ultrasound ablation surgery (FUAS), to identify the optimal classification of adenomyosis severity from different classification criteria and explore factors associated with the presence of symptoms. METHODS: The proportions of disease severity among different classification groups were compared to obtain the one generating the most considerable chi-square value, which was identified as the optimal classification for informing disease severity. A logistic regression model was constructed to explore factors associated with disease severity. RESULTS: Classification of Kobayashi H (classification 4) concerning the affected areas and size (volumes of lesions) was recognized as the optimal one, which identified dysmenorrhea (χ2=18.550, p-value=0.002) and menorrhagia (χ2=15.060, p-value=0.010) secondary to adenomyosis. For volumes of uterine wall <2/3, the dysmenorrhea rate in subtype-4 was higher than that in subtype-1 (χ2=4.114, p-value=0.043), and the dysmenorrhea rate in subtype-5 was higher than that in subtype-2 (χ2=4.357, p-value=0.037). Age (OR=0.899, 95%CI=0.810～0.997, p-value=0.044) and external phenotype (OR=3.588, 95%CI=CI 1.018～12.643, p-value=0.047) were associated with dysmenorrhea. Concerning volumes of uterine wall ≥2/3, the menorrhagia rate in subtype-3 remarkably increased compared with that in subtype-6 (χ2=9.776, p-value=0.002), and internal phenotype was identified as an independent factor associated with menorrhagia (OR=1.706, 95%CI=1.131～2.573, p-value=0.011). LIMITATIONS: Patients in our study were all included before FUAS, which limited our result interpretation for the general patient population. CONCLUSIONS: MRI-based classification 4 is identified as an optimal classification for informing the severity of adenomyosis. The phenotype of classification is the main characteristic associated with disease severity.

Humans combine value learning and hypothesis testing strategically in multi-dimensional probabilistic reward learning.

Realistic and complex decision tasks often allow for many possible solutions. How do we find the correct one? Introspection suggests a process of trying out solutions one after the other until success. However, such methodical serial testing may be too slow, especially in environments with noisy feedback. Alternatively, the underlying learning process may involve implicit reinforcement learning that learns about many possibilities in parallel. Here we designed a multi-dimensional probabilistic active-learning task tailored to study how people learn to solve such complex problems. Participants configured three-dimensional stimuli by selecting features for each dimension and received probabilistic reward feedback. We manipulated task complexity by changing how many feature dimensions were relevant to maximizing reward, as well as whether this information was provided to the participants. To investigate how participants learn the task, we examined models of serial hypothesis testing, feature-based reinforcement learning, and combinations of the two strategies. Model comparison revealed evidence for hypothesis testing that relies on reinforcement-learning when selecting what hypothesis to test. The extent to which participants engaged in hypothesis testing depended on the instructed task complexity: people tended to serially test hypotheses when instructed that there were fewer relevant dimensions, and relied more on gradual and parallel learning of feature values when the task was more complex. This demonstrates a strategic use of task information to balance the costs and benefits of the two methods of learning.

Single-plane versus real-time biplane approaches for ultrasound-guided central venous catheterization in critical care patients: a randomized controlled trial.

BACKGROUND: Critical care patients often require central venous cannulation (CVC). We hypothesized that real-time biplane ultrasound-guided CVC would improve first-puncture success rate and reduce mechanical complications. The purpose of this study was to compare the success rate and safety of single-plane and real-time biplane approaches for ultrasound-guided CVC. METHODS: From October 2022 to March 2023, 256 participants with critical illness requiring CVC were randomized to either the single-plane (n = 128) or biplane (n = 128) ultrasound-guided cannulation groups. The success rate, number of punctures, procedure duration, incidence of catheterization-related complications, and confidence score of operators were documented. RESULTS: The central vein was successfully cannulated in all 256 participants (163 [64%] man and 93 [36%] women; mean age 69 ± 19 [range 13-104 years]), including 182 and 74 who underwent internal jugular vein cannulation (IJVC) and femoral vein cannulation (FVC), respectively. The incidence of successful puncture on the first attempt was higher in the biplane group than that in the single-plane group (91.6% vs. 74.7%; relative risk (RR), 1.226; 95% confidence interval (CI), 1.069-1.405; P = 0.002 for the IJVC and 90.9% vs. 68.3%; RR, 1.331; 95% CI, 1.053-1.684; P = 0.019 for the FVC). The biplane group was also associated with a higher first-puncture single-pass catheterization success rate (87.4% vs. 69.0% and 90.9% vs. 68.3%), fewer undesired punctures (1[1-1(1-2)] vs. 1[1-2(1-4)] and 1[1-1(1-3)] vs. 1[1-2(1-4)]), shorter cannulation time (205 s [162-283 (66-1,526)] vs. 311 s [243-401 (136-1,223)] and 228 s [193-306 (66-1,669)] vs. 340 s [246-499 (130-944)]), and fewer immediate complications (10.5% vs. 28.7% and 9.1% vs. 34.1%) for both IJVC and FVC (all P < 0.05). CONCLUSION: Real-time biplane imaging of ultrasound-guided CVCs offers advantages over the single-plane approach for critically ill patients. TRIAL REGISTRATION: This prospective RCT was registered at Chinese Clinical Trial Registry (ChiCTR2200064843). Registered 19 October 2022.

Intelligent Fault Diagnosis of Rolling Element Bearings Based on Modified AlexNet.

The reliable and safe operation of industrial systems needs to detect and diagnose bearing faults as early as possible. Intelligent fault diagnostic systems that use deep learning convolutional neural network (CNN) techniques have achieved a great deal of success in recent years. In a traditional CNN, the fully connected layer is located in the final three layers, and such a layer consists of multiple layers that are all connected. However, the fully connected layer of the CNN has the disadvantage of too many training parameters, which makes the model training and testing time longer and incurs overfitting. Additionally, because the working load is constantly changing and noise from the place of operation is unavoidable, the efficiency of intelligent fault diagnosis techniques suffers great reductions. In this research, we propose a novel technique that can effectively solve the problem of traditional CNN and accurately identify the bearing fault. Firstly, the best pre-trained CNN model is identified by considering the classification's success rate for bearing fault diagnosis. Secondly, the selected CNN model is modified to effectively reduce the parameter quantities, overfitting, and calculating time of this model. Finally, the best classifier is identified to make a hybrid model concept to achieve the best performance. It is found that the proposed technique performs well under different load conditions, even in noisy environments, with variable signal-to-noise ratio (SNR) values. Our experimental results confirm that this proposed method is highly reliable and efficient in detecting and classifying bearing faults.

Assessment of dynamic drought-induced ecosystem risk: Integrating time-varying hazard frequency, exposure and vulnerability.

Terrestrial ecosystems, occupying 28.26% of Earth's surface, are extensively at risk from droughts, which is likely to propagate into human communities owing to loss of vital services. Ecosystem risk also tends to fluctuate within anthropogenically-forced nonstationary environments, raising considerable concerns about effectiveness of mitigation strategies. This study aims to assess dynamic ecosystem risk induced by droughts and identify risk hotspots. Bivariate nonstationary drought frequency was initially derived as a hazard component of risk. By coupling vegetation coverage and biomass quantity, a two-dimensional exposure indicator was developed. Trivariate likelihood of vegetation decline was calculated under arbitrary droughts to intuitively determine ecosystem vulnerability. Ultimately, time-variant drought frequency, exposure and vulnerability were multiplied to derive dynamic ecosystem risk, followed by hotspot and attribution analyses. Risk assessment implemented in the drought-prevalent Pearl River basin (PRB) of China during 1982-2017 showed that meteorological droughts in eastern and western margins, although less frequent, were prolonged and aggravated in contrast to prevalence of less persistent and severe droughts in the middle. In 86.12% of the PRB, ecosystem exposure maintains high levels (0.62). Relatively high vulnerability (>0.5) occurs in water-demanding agroecosystems, exhibiting a northwest-southeast-directed extension. A 0.1-degree risk atlas unveils that high and medium risks occupy 18.96% and 37.99% of the PRB, while risks are magnified in the north. The most pressing hotspots with high risk continuing to escalate reside in the East River and Hongliu River basins. Our results provide knowledge of composition, spatio-temporal variability and driving mechanism of drought-induced ecosystem risk, which will assist in risk-based mitigation prioritization.

Improving maize quality from mechanical grain harvesting by matching maize varieties with accumulated temperature in northeast China.

BACKGROUND: Global warming has led to methods of planting late-maturing maize varieties in northeast China that have hindered the development of physiological maturity (PM) at harvest and the use of mechanical grain harvesting (MGH). Under these conditions it is difficult to balance the drying characteristics of maize varieties and to make full use of accumulated temperature resources in such a way as to reduce grain moisture content (GMC) at harvest. RESULTS: The effective accumulated temperature (AcT) and the drying rates of different varieties vary. In northeast China, with a GMC of 25%, the growth periods of a fast-drying variety (FDV) and a slow-drying variety (SDV) were 114-192 days and 110-188 days respectively. After PM, the FDV needed 47 days and the SDV needed 51 days to reduce the GMC to be ready for MGH. Harvested with a GMC of 20%, the growth period for the FDV was 97-175 days and for the SDV it was 90-171 days. After PM, the FDV required 64 days and the SDV needed 70 days to reduce the GMC to be ready for MGH. CONCLUSION: Matching cultivars with AcT can help farmers to choose suitable varieties. Promoting MGH may boost maize production, thus ensuring China's food security. © 2023 Society of Chemical Industry.

A method of assessing the depth of contaminated sediments that should be removed in lakes: a case study of Tangxun Lake, China.

The depth of contaminated sediments constrains the water environment of large shallow lakes and can affect shallow lake water quality through sediment resuspension and nutrient release. Although such effects can be avoided by sediment dredging methods, we still cannot precisely quantify the depth of sediment dredging. Therefore, we used organic index method, pollution index method and potential ecological risk evaluation to evaluate the contamination status of split samples of in situ sediments layer by layer, and established a comprehensive contamination index evaluation method for layer-by-layer sediments, then combined with the contamination release characteristics of split samples to assess the contamination degree of the sediments obtained. The results show that the content of nitrogen and phosphorus in the surface layer of Lake Townsend sediments is generally higher than that in the middle and bottom sediments, and the heavy metals also satisfy this pattern, which is consistent in the sediments of both east and west regions. We also simulated the release process of nitrogen and phosphorus nutrients in the in situ sediment of Tangxun Lake in 2019, and the experimental results showed that the risk of nitrogen and phosphorus nutrient release in the sediment was mainly concentrated in the surface and middle layers, and the risk of elemental nitrogen release was significantly greater than that of phosphorus release. Finally, a comprehensive evaluation was carried out to obtain the desilting depth of the sediments in Lake Townsend, and it can be determined that the recommended desilting depth is about 20 cm for West Lake and 30 cm for East Lake. The results show that the recommended dredging depth can be determined based on this method, which provides an important scientific basis for sediment dredging in Tangxun Lake and even provides a new paradigm for sediment dredging depth estimation in similar large shallow lakes.

[Research Progress in the Application of Ultrasound-Guided Robot in Minimally Invasive Surgery].

With the continuous advances in modern medical technology and equipment,minimally invasive surgery (MIS) is widely applied in clinical practice.Ultrasound (US) as a real-time,portable,and radiation-free medical imaging method can be used for the intraoperative guidance in MIS to ensure safe and effective surgery.However,the physical characteristics of conventional US fail to display some tissue structures of the human body due to the existence of gas and bone.US-based navigation can make up for the deficiencies by advanced imaging technologies including spatial orientation,image reconstruction,and multi-modality image fusion,being real-time,accurate,and radiation-free.Therefore,US-guided robots can achieve safe,effective,and minimally invasive operation in MIS.This paper reviews the studies of US-guided robots in MIS and prospects the development of this field.

[Research Status and Prospect of New Ultrasound Technology in Predicting Cervical Lymph Node Metastasis of Thyroid Papillary Carcinoma].

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer,accounting for 90%.Most cases of PTC are inert tumors,while a few are invasive.Cervical lymph node metastasis is one of the major manifestations of invasive PTC.Preoperative accurate prediction of cervical lymph node metastasis is of great significance for the selection of therapeutic regimen and the evaluation of prognosis.New ultrasound technology is a non-invasive,convenient,and radiation-free examination method,playing a key role in predicting the cervical lymph node metastasis of PTC.This paper reviews the research status and makes an outlook on new ultrasound technology in predicting cervical lymph node metastasis of PTC.

[Advances in Molecular Targeted Ultrasound Contrast Agents].

In real-time ultrasound,molecular targeted contrast agent is introduced into the blood circulation through peripheral intravenous injection to enhance the imaging signal of target lesions after binding to the corresponding intravascular receptors,which can realize early diagnosis,staging of diseases,assessment of treatment response,and targeted treatment.In addition,molecular targeted ultrasound contrast agents provide a platform for the delivery of drugs and genes via microbubbles,and nanoscale contrast agents can be infiltrated through vascular endothelium into the interstitial space of the lesion for imaging or treatment.The available studies of molecular targeted ultrasound contrast agents mainly focus on the preclinical trials.Some clinical trials have been conducted in humans and preliminarily confirm the safety and feasibility of targeted ultrasound contrast agents.The molecular targeted ultrasound contrast agents enjoy a broad prospect in clinical application.

[Effect of Calcification on the Ultrasound-Guided Radiofrequency Ablation of Papillary Thyroid Carcinoma].

Objective To investigate the effect of calcification on the ultrasound-guided radiofrequency ablation(RFA)of papillary thyroid carcinoma(PTC).Methods We retrospectively analyzed the preoperative and follow-up data of 164 patients(182 nodules)with PTC treated by percutaneous ultrasound-guided RFA in the First Medical Center of Chinese PLA General Hospital from January 1,2018 to December 31,2021.The tumor status 12 months after RFA was taken as the endpoint event.The univariate Logistic regression analysis was employed to predict the influencing factors of incomplete ablation.The factors were then included in the multivariate Logistic regression analysis for prediction of the independent risk factors of incomplete ablation.Results The maximum nodule diameter(OR=1.16,95%CI=1.04-1.29,P=0.009)and calcification ratio >2/3(OR=19.27,95%CI=4.02-92.28,P<0.001)were the factors influencing the disappearance of lesion 12 months after RFA.Conclusions PTC with calcification can be treated with ultrasound-guided RFA.In the case of calcification ratio ≤ 2/3,this therapy demonstrates the effect equivalent to that of no calcification.

Recent Advances in Multiresponsive Flexible Sensors towards E-skin: A Delicate Design for Versatile Sensing.

Multiresponsive flexile sensors with strain, temperature, humidity, and other sensing abilities serving as real electronic skin (e-skin) have manifested great application potential in flexible electronics, artificial intelligence (AI), and Internet of Things (IoT). Although numerous flexible sensors with sole sensing function have already been reported since the concept of e-skin, that mimics the sensing features of human skin, was proposed about a decade ago, the ones with more sensing capacities as new emergences are urgently demanded. However, highly integrated and highly sensitive flexible sensors with multiresponsive functions are becoming a big thrust for the detection of human body motions, physiological signals (e.g., skin temperature, blood pressure, electrocardiograms (ECG), electromyograms (EMG), sweat, etc.) and environmental stimuli (e.g., light, magnetic field, volatile organic compounds (VOCs)), which are vital to real-time and all-round human health monitoring and management. Herein, this review summarizes the design, manufacturing, and application of multiresponsive flexible sensors and presents the future challenges of fabricating these sensors for the next-generation e-skin and wearable electronics.

Distal mutation V486M disrupts the catalytic activity of DPP4 by affecting the flap of the propeller domain.

Dipeptidyl peptidase-4 (DPP4) plays a crucial role in regulating the bioactivity of glucagon-like peptide-1 (GLP-1) that enhances insulin secretion and pancreatic ß-cell proliferation, making it a therapeutic target for type 2 diabetes. Although the crystal structure of DPP4 has been determined, its structure-function mechanism is largely unknown. Here, we examined the biochemical properties of sporadic human DPP4 mutations distal from its catalytic site, among which V486M ablates DPP4 dimerization and causes loss of enzymatic activity. Unbiased molecular dynamics simulations revealed that the distal V486M mutation induces a local conformational collapse in a ß-propeller loop (residues 234-260, defined as the flap) and disrupts the dimerization of DPP4. The "open/closed" conformational transitions of the flap whereby capping the active site, are involved in the enzymatic activity of DPP4. Further site-directed mutagenesis guided by theoretical predictions verified the importance of the conformational dynamics of the flap for the enzymatic activity of DPP4. Therefore, the current studies that combined theoretical modeling and experimental identification, provide important insights into the biological function of DPP4 and allow for the evaluation of directed DPP4 genetic mutations before initiating clinical applications and drug development.