CRISPR-TE: a web-based tool to generate single guide RNAs targeting transposable elements.

BACKGROUND: The CRISPR/Cas systems have emerged as powerful tools in genome engineering. Recent studies highlighting the crucial role of transposable elements (TEs) have stimulated research interest in manipulating these elements to understand their functions. However, designing single guide RNAs (sgRNAs) that are specific and efficient for TE manipulation is a significant challenge, given their sequence repetitiveness and high copy numbers. While various sgRNA design tools have been developed for gene editing, an optimized sgRNA designer for TE manipulation has yet to be established. RESULTS: We present CRISPR-TE, a web-based application featuring an accessible graphical user interface, available at https://www.crisprte.cn/ , and currently tailored to the human and mouse genomes. CRISPR-TE identifies all potential sgRNAs for TEs and provides a comprehensive solution for efficient TE targeting at both the single copy and subfamily levels. Our analysis shows that sgRNAs targeting TEs can more effectively target evolutionarily young TEs with conserved sequences at the subfamily level. CONCLUSIONS: CRISPR-TE offers a versatile framework for designing sgRNAs for TE targeting. CRISPR-TE is publicly accessible at https://www.crisprte.cn/ as an online web service and the source code of CRISPR-TE is available at https://github.com/WanluLiuLab/CRISPRTE/ .

Left atrial myxoma as a rare cause of stroke.

Cerebrovascular events may attribute to the fragmentation of a cardiac tumor. Due to the small number of reported cases of large vascular occlusion-acute ischemic stroke (LVO-AIS) associated with atrial myxoma, current guidelines still follow the principle of intravenous thrombolysis priority, even if LVO-AIS patients are eligible for mechanical thrombectomy, and have not recommended the timing of cardiac surgery or preoperative anticoagulation and antithrombotic therapy. Surgical removal is the definitive therapy for cardiac myxomas, especially for left-sided myxomas. With this case, we aim to demonstrate the main challenges that clinicians may encounter when dealing with patients with AIS secondary to cardiac myxoma: the difficulties with clinical diagnosis, strategies for reperfusion therapy, and therapeutic management of cardiac myxoma.

[Progress of the application research of modern acupuncture anesthesia in perioperative period of thoracic surgery].

Modern acupuncture anesthesia is the application of acupuncture-related therapies to optimize the perioperative management which is based on the combined acupuncture-medicine anesthesia technology, and building a perioperative acupuncture anesthesia accelerated rehabilitation system. Based on the thoracic surgery, this paper analyzes and summarizes the application effects of modern acupuncture anesthesia, focusing on preoperative anxiety relief and advanced analgesia； reduce the dosage of anesthetics, stable respiration and hemodynamics, anti-stress and organ protection during surgery； postoperative analgesia, prevention of nausea, vomiting and cognitive impairment, improvement of gastrointestinal function, prevention of cognitive impairment, and enhancement of immunity. It is anticipated that this review may provide a basis for the further promotion and application of modern acupuncture anesthesia in clinical practice.

The involvement of ADAR1 in chronic unpredictable stress-induced cognitive impairment by targeting DARPP-32 with miR-874-3p in BALB/c mice.

Introduction: Chronic stress exposure is the main environmental factor leading to cognitive impairment, but the detailed molecular mechanism is still unclear. Adenosine Deaminase acting on double-stranded RNA1(ADAR1) is involved in the occurrence of chronic stress-induced cognitive impairment. In addition, dopamine and Adenosine 3'5'-monophosphate-regulated phospho-protein (DARPP-32) gene variation affects cognitive function. Therefore, we hypothesized that ADAR1 plays a key role in chronic stress-induced cognitive impairment by acting on DARPP-32. Methods: In this study, postnatal 21-day-old male BALB/c mice were exposed to chronic unpredictable stressors. After that, the mice were treated with ADAR1 inducer/inhibitor. The cognitive ability and cerebral DARPP-32 protein expression of BALB/c mice were evaluated. In order to explore the link between ADAR1 and DARPP-32, the effects of ADAR1 high/low expression on DARPP-32 protein expression in vitro were detected. Results: ADAR1 inducer alleviates cognitive impairment and recovers decreased DARPP-32 protein expression of the hippocampus and prefrontal cortex in BALB/c mice with chronic unpredictable stress exposure. In vivo and in vitro studies confirm the results predicted by bio-informatics; that is, ADAR1 affects DARPP-32 expression via miR-874-3p. Discussion: The results in this study demonstrate that ADAR1 affects the expression of DARPP-32 via miR-874-3p, which is involved in the molecular mechanism of pathogenesis in chronic unpredictable stress-induced cognitive impairment. The new findings of this study provide a new therapeutic strategy for the prevention and treatment of stress cognitive impairment from epigenetics.

Efficacy and safety of transcutaneous electrical acupoints stimulation for preoperative anxiety in thoracoscopic surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Preoperative anxiety occurs at a very high rate in patients undergoing video-assisted thoracoscopic surgery (VATS). Moreover, it will result in poor mental state, more analgesic consumptions, rehabilitation delay and extra hospitalisation costs. Transcutaneous electrical acupoints stimulation (TEAS) is a convenient intervention for pain control and anxiety reduction. Nevertheless, TEAS efficacy of preoperative anxiety in VATS is unknown. METHODS AND ANALYSIS: This single-centre randomised sham-controlled trial will be conducted in cardiothoracic surgery department of the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine in China. A total of 92 eligible participants with pulmonary nodules (size ≥8 mm) who are arranged for VATS will be randomly assigned to a TEAS group and a sham TEAS (STEAS) group in a 1:1 ratio. Daily TEAS/STEAS intervention will be administered starting on 3 days before the VATS and continued once per day for three consecutive days. The primary outcome will be the generalised anxiety disorder scale score change between the day before surgery with the baseline. The secondary outcomes will include serum concentrations of 5-hydroxytryptamine, norepinephrine and gamma-aminobutyric acid, intraoperative anaesthetic consumption, time to postoperative chest tube removal, postoperative pain, and length of postoperative hospital stay. The adverse events will be recorded for safety evaluation. All data in this trial will be analysed by the SPSS V.21.0 statistical software package. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine (approval number: 2021-023). The results of this study will be distributed through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04895852.

Potential pollution assessment of labile trace metals in Xixi River estuary sediments in Xiamen, China.

The release of trace metals caused by industrial effluents and anthropogenic activities has been recorded in the Xixi River estuary, southern China. However, a thorough understanding of the behavior of trace heavy metals in Xixi River sediments is lacking. A total of 12 sediment cores were collected in June and December in the upper estuary section and mouth of the estuary. Here, an in situ high-resolution sampling technique, namely, diffusive gradients in thin films (DGT), was employed to acquire profiles of trace element concentrations and the release of bioavailable metals from sediments in different seasons. A three-step Community Bureau of Reference (BCR) sequential extraction method was used to explore the chemical speciation of trace metals in different seasons and to thereby assess the release potential of trace elements in sediments. The BCR sequential extraction results showed that the trace metals Fe, Mn, Co and Pb were mainly in the residual fraction, which rarely influences living organisms. The total mobile fractions (F1 + F2 + F3) of all trace metals were higher in winter than in summer, suggesting that accumulation occurred from summer to winter. DGT measurements showed that the intensity of sulfate reduction was higher in summer than in winter because of the high temperatures and high organic matter in summer. The intensity of sulfate and Mn(III/IV) reduction increased from the upper estuary section to the lower estuary. Fe(III) reduction decreased in summer but increased slowly in winter. The Pearson correlation results showed that the release of DGT-labile Co in pore water was related to Mn(III/IV) reduction, while the release of DGT-labile Pb was basically not controlled by the Fe-Mn-S redox transition. Abnormally high DGT-labile Pb concentrations were observed at the sampling station (XR3) closest to the estuary in winter, which might have been caused by the high Pb content in the local micro-sediments.

CryoETGAN: Cryo-Electron Tomography Image Synthesis via Unpaired Image Translation.

Cryo-electron tomography (Cryo-ET) has been regarded as a revolution in structural biology and can reveal molecular sociology. Its unprecedented quality enables it to visualize cellular organelles and macromolecular complexes at nanometer resolution with native conformations. Motivated by developments in nanotechnology and machine learning, establishing machine learning approaches such as classification, detection and averaging for Cryo-ET image analysis has inspired broad interest. Yet, deep learning-based methods for biomedical imaging typically require large labeled datasets for good results, which can be a great challenge due to the expense of obtaining and labeling training data. To deal with this problem, we propose a generative model to simulate Cryo-ET images efficiently and reliably: CryoETGAN. This cycle-consistent and Wasserstein generative adversarial network (GAN) is able to generate images with an appearance similar to the original experimental data. Quantitative and visual grading results on generated images are provided to show that the results of our proposed method achieve better performance compared to the previous state-of-the-art simulation methods. Moreover, CryoETGAN is stable to train and capable of generating plausibly diverse image samples.

Kinetic characteristics of mobile Mo associated with Mn, Fe and S redox geochemistry in estuarine sediments.

Estuarine sediments are crucial repositories and incubators of molybdenum (Mo) during its transport from rivers to the ocean. Here, Mo mobility and related processes in estuarine sediments were explored using high-resolution dialysis (HR-Peeper) and diffusive gradients in thin films (DGT) techniques. Better correlations were observed between dissolved Mn and Mo than between dissolved Fe and Mo, implying that Mn geochemistry plays a key role in dissolved Mo mobility via molybdate adsorption onto abundant Mn oxides and its substantial release upon intense Mn reduction. As a result, oxic intertidal sediments functioned as Mo sinks, and anoxic subtidal sediments functioned as Mo sources. The opposite vertical distributions between DGT-Labile S and DGT-Labile Mo indicated that the availability of labile Mo can be blocked by aqueous sulfide. However, the corresponding high concentrations of DGT-Labile S and dissolved Mo at subtidal sites demonstrated that the abundant dissolved Mo remobilized via Mn reduction was not effectively solidified by sulfide. Simulation with the DIFS model further verified that redox conditions and induced physicochemical processes are crucial factors controlling Mo mobility, with relatively low dissolved Mo concentrations but an adequate and steady resupply capacity of the bioavailable molybdate in intertidal sediments.

Remobilization and hypoxia-dependent migration of phosphorus at the coastal sediment-water interface.

Sediment internal phosphorus (P) loading can be tightly associated with overlying water hypoxia. However, the effects of long-term seasonal hypoxia on the geochemical transition of P in P-poor coastal sediment and how this transition is linked to the early diagenesis of iron (Fe), sulfur (S) and carbon are still poorly understood. Here, we conducted a one-year monthly field investigation to study the (im)mobilization and migration of P among coastal sediment, porewater and overlying water. The coherent distribution of soluble Fe and mobile P and decoupled distribution of labile S (soluble sulfide) and mobile P in the depth profiles indicate that the redox cycling of Fe (but not S) dominates P mobility. Nevertheless, the monthly variation in the porewater soluble reactive P (SRP) presented significant positive correlations with that of the overlying water SRP. This finding highlights that hypoxia-fueled SRP migration from overlying water rather than weak diagenetic P mobilization due to deficient organic matter and solid labile P is the crucial factor responsible for internal P mobility over long time scales. Although SRP tends to migrate from overlying water to porewater, the potential risk of sediment labile P remobilization and reliberation to the overlying water is considerable.