Trivalent Phosphine-Catalyzed [4+1] Spiro-annulation Reaction Using Allenyl Imide and Methylene Cyclocompounds.

The trivalent phosphine-catalyzed [4+1] spiro-annulation reaction of allenyl imide and activated methylene cyclocompounds has been developed for the construction of various spiro-2-cyclopenten-1-ones. Oxindoles, 3-isochromanones, and 2-indanones are selected as 1C synthons to capture the in situ-generated bis-electrophilic α,ß-unsaturated ketenyl phosphonium intermediate, affording the corresponding monospiro- and bispiro-cyclopentenones in good to excellent yields (≤91%) under mild conditions. The primary attempt at asymmetric catalysis using monophosphine (R)-SITCP provides promising enantioselectivity (45% ee). A plausible reaction mechanism is also proposed.

An ultralight, pulverization-free integrated anode toward lithium-less lithium metal batteries.

The high-capacity advantage of lithium metal anode was compromised by common use of copper as the collector. Furthermore, lithium pulverization associated with "dead" Li accumulation and electrode cracking deteriorates the long-term cyclability of lithium metal batteries, especially under realistic test conditions. Here, we report an ultralight, integrated anode of polyimide-Ag/Li with dual anti-pulverization functionality. The silver layer was initially chemically bonded to the polyimide surface and then spontaneously diffused in Li solid solution and self-evolved into a fully lithiophilic Li-Ag phase, mitigating dendrites growth or dead Li. Further, the strong van der Waals interaction between the bottommost Li-Ag and polyimide affords electrode structural integrity and electrical continuity, thus circumventing electrode pulverization. Compared to the cutting-edge anode-free cells, the batteries pairing LiNi0.8Mn0.1Co0.1O2 with polyimide-Ag/Li afford a nearly 10% increase in specific energy, with safer characteristics and better cycling stability under realistic conditions of 1× excess Li and high areal-loading cathode (4 milliampere hour per square centimeter).

Improved method for modulation transfer function measurement of Bayer color cameras.

Aiming at the difficulty of detecting the modulation transfer function (MTF) of Bayer color cameras during focusing, the traditional scheme is modified in this paper. First, through analysis, it is found that the MTF of the Bayer detector decreased substantially compared to the monochromatic detector, which was caused by the loss of a large amount of light from the Bayer detector. When the MTF is calculated for the color image after de-mosaicing, the degradation of image quality leads to the inability to obtain the full-frequency MTF curve. Therefore, this paper proposes a solution to detect the MTFs of the three primary colors in the Bayer image individually, and then weight the MTFs of each primary color to obtain the MTF of the color image based on the calibration results of the light source. Then, considering the steps of differentiation and Fourier transform in the slanted-edge method, this paper solves the problem of non-uniform sampling of edge spread function by using the modification of the slanted-edge method with non-uniform Fourier transform. Finally, the optimal imaging position of a certain type of Bayer color camera is determined using the methods proposed in this paper. Simulation and test results verify the effectiveness and accuracy of the methods in this paper.

[Augmenting locking plate with autologous bone graft for the treatment of nonunion of long bone fracture in the lower extremity with retaining of the original intramedullary nail].

OBJECTIVE: To explore clinical effect of attaching locking plate with bone grafting based on retaining the original intramedullary nail in treating non-union after intramedullary nail fixation of long shaft fractures of lower limbs. METHODS: A retrospective study was conducted on 20 patients treated with non-union fractures after intramedullary nailing of long shaft fractures of lower limbs from June 2015 to June 2020. All patients were treated with the original intramedullary nailing and bone grafting from the iliac bone, and were underwent open reduction plate internal fixation and bone grafting for old fractures. Among them, 14 were males and 6 were females, aged from 35 to 56 years old with an average of (42.2±9.6) years old. Nine patients were femoral shaft fracture and 11 patients were tibial shaft fracture. According to characteristics of fracture end nonunion, 6 patients were stable/atrophic, 9 patients were unstable/large, and 5 patients were unstable/atrophic. The nonunion time ranged from 8 to 12 months with an average of(9.8±2.0) months after the initial surgery. Visual analogue scale (VAS), knee range of motion, bone healing time, complications and fracture-end healing were recorded before and at the latest follow-up. RESULTS: All patients were followed up for 18 to 48 months with an average of (36.3±10.5) months. The incision of all patients were healed at stageⅠwithout complications such as infection or internal fixation ruptur. Healing time of femur and tibia was (8.5±2.6) months and (9.5±2.2) months. Knee joint motion increased from preoperative (101.05±8.98) ° to postoperative (139.35±8.78) ° at the latest follow-up (t=-12.845, P<0.001). VAS decreased from preoperative (5.15±1.72) to postoperative (0.75±0.96) at the latest follow-up (t=11.186, P<0.001). CONCLUSION: On the basis of retaining the original intramedullary nail, the addition of locking plate internal fixation and autogenous iliac bone grafting have advantages of simple operation, less trauma, fewer complications and high fracture healing rate. It is one of the effective surgical schemes for the treatment of nonunion after intramedullary nail fixation of long bone fracture of lower extremity.

A Motivational Interviewing Chatbot With Generative Reflections for Increasing Readiness to Quit Smoking: Iterative Development Study.

BACKGROUND: The motivational interviewing (MI) approach has been shown to help move ambivalent smokers toward the decision to quit smoking. There have been several attempts to broaden access to MI through text-based chatbots. These typically use scripted responses to client statements, but such nonspecific responses have been shown to reduce effectiveness. Recent advances in natural language processing provide a new way to create responses that are specific to a client's statements, using a generative language model. OBJECTIVE: This study aimed to design, evolve, and measure the effectiveness of a chatbot system that can guide ambivalent people who smoke toward the decision to quit smoking with MI-style generative reflections. METHODS: Over time, 4 different MI chatbot versions were evolved, and each version was tested with a separate group of ambivalent smokers. A total of 349 smokers were recruited through a web-based recruitment platform. The first chatbot version only asked questions without reflections on the answers. The second version asked the questions and provided reflections with an initial version of the reflection generator. The third version used an improved reflection generator, and the fourth version added extended interaction on some of the questions. Participants' readiness to quit was measured before the conversation and 1 week later using an 11-point scale that measured 3 attributes related to smoking cessation: readiness, confidence, and importance. The number of quit attempts made in the week before the conversation and the week after was surveyed; in addition, participants rated the perceived empathy of the chatbot. The main body of the conversation consists of 5 scripted questions, responses from participants, and (for 3 of the 4 versions) generated reflections. A pretrained transformer-based neural network was fine-tuned on examples of high-quality reflections to generate MI reflections. RESULTS: The increase in average confidence using the nongenerative version was 1.0 (SD 2.0; P=.001), whereas for the 3 generative versions, the increases ranged from 1.2 to 1.3 (SD 2.0-2.3; P<.001). The extended conversation with improved generative reflections was the only version associated with a significant increase in average importance (0.7, SD 2.0; P<.001) and readiness (0.4, SD 1.7; P=.01). The enhanced reflection and extended conversations exhibited significantly better perceived empathy than the nongenerative conversation (P=.02 and P=.004, respectively). The number of quit attempts did not significantly change between the week before the conversation and the week after across all 4 conversations. CONCLUSIONS: The results suggest that generative reflections increase the impact of a conversation on readiness to quit smoking 1 week later, although a significant portion of the impact seen so far can be achieved by only asking questions without the reflections. These results support further evolution of the chatbot conversation and can serve as a basis for comparison against more advanced versions.

Anchoring ultrasmall Pd nanoparticles by bipyridine functional covalent organic frameworks for semihydrogenation of acetylene.

Acetylene hydrogenation is a well-accepted solution to reduce by-products in the ethylene production process, while one of the key technical difficulties lies in developing a catalyst that can provide highly dispersed active sites. In this work, a highly crystalline layered covalent organic framework (COF) material (TbBpy) with excellent thermal stability was synthesized and firstly applied as support for ultrasmall Pd nanoparticles to catalyze acetylene hydrogenation. 100% of C2H2 conversion and 88.2% of C2H4 selectivity can be obtained at 120 °C with the space velocity of 70 000 h-1. The reaction mechanism was elucidated by applying a series of characterization techniques and theoretical calculation. The results indicate that the coordination between Pd and N atom in the bipyridine functional groups of COFs successfully increased the dispersibility and stability of Pd particles, and the introduction of COFs not only improved the adsorption of acetylene and H2 onto catalyst surface, but enhanced the electron transfer process, which can be responsible for the high selectivity and activity of catalyst. This work, for the first time, reported the excellent performance of Pd@TbBpy as a catalyst for acetylene hydrogenation and will facilitate the development and application of COFs materials in the area of petrochemicals.

Carbonic Anhydrase Inhibition as a Target for Antibiotic Synergy in Enterococci.

Enterococcus faecalis is a hospital-associated opportunistic pathogen that can cause infections with high mortality, such as infective endocarditis. With an increasing occurrence of multidrug-resistant enterococci, there is a need for alternative strategies to treat enterococcal infections. We isolated a gentamicin-hypersusceptible E. faecalis strain from a patient with infective endocarditis that carried a mutation in the alpha-carbonic anhydrase (α-CA) and investigated how disruption of α-CA sensitized E. faecalis to killing with gentamicin. The gentamicin-hypersusceptible α-CA mutant strain showed increased intracellular gentamicin uptake in comparison to an isogenic strain encoding full-length, wild-type α-CA. We hypothesized that increased gentamicin uptake could be due to increased proton motive force (PMF), increased membrane permeability, or both. We observed increased intracellular ATP production in the α-CA mutant strain, suggesting increased PMF-driven gentamicin uptake contributed to the strain's gentamicin susceptibility. We also analyzed the membrane permeability and fatty acid composition of isogenic wild-type and α-CA mutant strains and found that the mutant displayed a membrane composition that was consistent with increased membrane permeability. Finally, we observed that exposure to the FDA-approved α-CA inhibitor acetazolamide lowered the gentamicin MIC of eight genetically diverse E. faecalis strains with intact α-CA but did not change the MIC of the α-CA mutant strain. These results suggest that α-CA mutation or inhibition increases PMF and alters membrane permeability, leading to increased uptake of gentamicin into E. faecalis. This connection could be exploited clinically to provide new combination therapies for patients with enterococcal infections. IMPORTANCE Enterococcal infections can be difficult to treat, and new therapeutic approaches are needed. In studying an E. faecalis clinical strain from an infected patient, we found that the bacteria were rendered hypersusceptible to aminoglycoside antibiotics through a mutation that disrupted the α-CA. Our follow-on work suggested two different ways that α-CA disruption causes increased gentamicin accumulation in E. faecalis: increased proton motive force-powered uptake and increased membrane permeability. We also found that a mammalian CA inhibitor could sensitize a variety of E. faecalis strains to killing with gentamicin. Given that mammalian CA inhibitors are frequently used to treat conditions such as glaucoma, hypertension, and epilepsy, our findings suggest that these "off-the-shelf" inhibitors could also be useful partner antibiotics for the treatment of E. faecalis infections.

Sarcopenia provides extra value outside the PULP score for predicting mortality in older patients with perforated peptic ulcers.

BACKGROUND: Perforated peptic ulcer (PPU) remains challenging surgically due to its high mortality, especially in older individuals. Computed tomography (CT)-measured skeletal muscle mass is a effective predictor of the surgical outcomes in older patients with abdominal emergencies. The purpose of this study is to assess whether a low CT-measured skeletal muscle mass can provide extra value in predicting PPU mortality. METHODS: This retrospective study enrolled older (aged ≥ 65 years) patients who underwent PPU surgery. Cross-sectional skeletal muscle areas and densities were measured by CT at L3 and patient-height adjusted to obtain the L3 skeletal muscle gauge (SMG). Thirty-day mortality was determined with univariate, multivariate and Kaplan-Meier analysis. RESULTS: From 2011 to 2016, 141 older patients were included; 54.8% had sarcopenia. They were further categorized into the PULP score ≤ 7 (n=64) or PULP score > 7 group (n=82). In the former, there was no significant difference in 30-day mortality between sarcopenic (2.9%) and nonsarcopenic patients (0%; p=1.000). However, in the PULP score > 7 group, sarcopenic patients had a significantly higher 30-day mortality (25.5% vs. 3.2%, p=0.009) and serious complication rate (37.3% vs. 12.9%, p=0.017) than nonsarcopenic patients. Multivariate analysis showed that sarcopenia was an independent risk factor for 30-day mortality in patients in the PULP score > 7 group (OR: 11.05, CI: 1.03-118.7). CONCLUSION: CT scans can diagnose PPU and provide physiological measurements. Sarcopenia, defined as a low CT-measured SMG, provides extra value in predicting mortality in older PPU patients.

Research on the Modulation Transfer Function Detection Method of a Bayer Filter Color Camera.

Bayer filter color cameras are more and more widely used in the field of aerospace remote sensing, but the Bayer filter causes great degradation in image quality; therefore, obtaining a means of achieving the high-precision measurement of the modulation transfer function (MTF) of Bayer filter color cameras is an urgent problem. In order to solve this problem, this paper develops a slanted-edge method via three steps: the detection of the slanted edge, the acquisition and processing of the edge spread function (ESF), and the acquisition and processing of the line spread function (LSF). A combination of the Canny operator and Hough transform is proposed for the detection of the slanted edge, which improves the fitting accuracy and anti-interference ability of the algorithm. Further, the Canny operator is improved by constructing an adaptive filter function and introducing the Otsu method, which can more effectively smooth the image and remove its false edges. A method of processing ESF data by combining cubic spline interpolation and Savitzky-Golay (SG) filtering is proposed, which reduces the effects of noise and the non-uniform sampling of ESF on MTF. A method of LSF processing using Gaussian function fitting is proposed to further reduce the effect of noise on MTF. The improved algorithm is verified by the MTF measurement test applied to a specific type of Bayer filter color space camera. The simulation and test results show that the improved slanted-edge method discussed in this paper has greater precision and a better anti-interference ability, and it can effectively solve the difficult problem associated with MTF detection in Bayer filter color space cameras.

Bitter-RF: A random forest machine model for recognizing bitter peptides.

Introduction: Bitter peptides are short peptides with potential medical applications. The huge potential behind its bitter taste remains to be tapped. To better explore the value of bitter peptides in practice, we need a more effective classification method for identifying bitter peptides. Methods: In this study, we developed a Random forest (RF)-based model, called Bitter-RF, using sequence information of the bitter peptide. Bitter-RF covers more comprehensive and extensive information by integrating 10 features extracted from the bitter peptides and achieves better results than the latest generation model on independent validation set. Results: The proposed model can improve the accurate classification of bitter peptides (AUROC = 0.98 on independent set test) and enrich the practical application of RF method in protein classification tasks which has not been used to build a prediction model for bitter peptides. Discussion: We hope the Bitter-RF could provide more conveniences to scholars for bitter peptide research.

Improving the understanding of PI-RADS in practice: characters of PI-RADS 4 and 5 lesions with negative biopsy.

The Prostate Imaging Reporting and Data System (PI-RADS) has good ability to identify the nature of lesions on prostate magnetic resonance imaging (MRI). However, some lesions are still reported as PI-RADS 4 and 5 but are biopsy-proven benign. Herein, we aimed to summarize the reasons for the negative prostate biopsy of patients who were assessed as PI-RADS 4 and 5 by biparameter MRI. We retrospectively sorted out the prostate MRI, treatment, and follow-up results of patients who underwent a biparameter MRI examination of the prostate in The First Affiliated Hospital of Nanjing Medical University (Nanjing, China) from August 2019 to June 2021 with PI-RADS 4 and 5 but a negative biopsy. We focused on reviewing the MRI characteristics. A total of 467 patients underwent transperineal prostate biopsy. Among them, biopsy pathology of 93 cases were negative. After follow-up, 90 patients were ruled out of prostate cancer. Among the 90 cases, 40 were considered to be overestimated PI-RADS after review. A total of 22 cases were transition zone (TZ) lesions with regular appearance and clear boundaries, and 3 cases were symmetrical lesions. Among 15 cases, the TZ nodules penetrated the peripheral zone (PZ) and were mistaken for the origin of PZ. A total of 17 cases of lesions were difficult to distinguish from prostate cancer. Among them, 5 cases were granulomatous inflammation (1 case of prostate tuberculosis). A total of 33 cases were ambiguous lesions, whose performance was between PI-RADS 3 and 4. In summary, the reasons for "false-positive MRI diagnosis" included PI-RADS overestimation, ambiguous images giving higher PI-RADS, diseases that were really difficult to distinguish, and missed lesion in the initial biopsy; and the first two accounted for the most.

Physcion prevents high-fat diet-induced endothelial dysfunction by inhibiting oxidative stress and endoplasmic reticulum stress pathways.

High-fat diet (HFD)-induced obesity leads endothelial dysfunction and contributes to cardiovascular diseases. Palmitic acid (PA), a free fatty acid, is the main component of dietary saturated fat. Physcion, a chemical ingredient from Rhubarb, has been shown anti-hypertensive, anti-bacteria, and anti-tumor properties. However, the effects of physcion on endothelial dysfunction under HFD-induced obesity have not been reported. The purpose of the present study was to define the protective effect of physcion on HFD-induced endothelial dysfunction and its mechanisms involved. Obesity rat model was induced by HFD for 12 weeks. A rat thoracic aortic ring model was used to investigate the effects of physcion on HFD-induced impairment of vasorelaxation. Endothelial cell injury model was constructed in human umbilical vein endothelial cells (HUVECs) by treating with PA (0.25 mM) for 24 h. The results revealed that physcion reduced body weight and the levels of plasma TG, prevented impairment of endothelium-dependent relaxation in HFD-fed rats. In PA-injured HUVECs, physcion inhibited impaired viability, apoptosis and inflammation. Physcion also suppressed PA-induced both oxidative stress and ER stress in HUVECs. Furthermore, physcion increased PA-induced decrease in the activation of eNOS/Nrf2 signaling in HUVECs. These findings suggest that physcion has a significant beneficial effect on regulating HFD-induced endothelial dysfunction, which may be related to the inhibition of oxidative stress and ER stress through activation of eNOS/Nrf2 signaling pathway.

Emodin protects against homocysteine-induced cardiac dysfunction by inhibiting oxidative stress via MAPK and Akt/eNOS/NO signaling pathways.

Elevated levels of plasma homocysteine (Hcy) causes severe cardiac dysfunction, which is closely associated with oxidative stress. Emodin, a naturally occurring anthraquinone derivative, has been shown to exert antioxidant and anti-apoptosis activities. However, whether emodin could protect against Hcy-induced cardiac dysfunction remains unknown. The current study aimed to investigate the effects of emodin on the Hcy-induced cardiac dysfunction and its molecular mechanisms. Rats were fed a methionine diet to establish the animal model of hyperhomocysteinemia (HHcy). H9C2 cells were incubated with Hcy to induce a cell model of Hcy-injured cardiomyocytes. ELISA, HE staining, carotid artery and left ventricular cannulation, MTT, fluorescence staining, flow cytometry and western blotting were used in this study. Emodin significantly alleviated the structural damage of the myocardium and cardiac dysfunction from HHcy rats. Emodin prevented apoptosis and the collapse of MMP in the Hcy-treated H9C2 cells in vitro. Further, emodin reversed the Hcy-induced apoptosis-related biochemical changes including decreased Bcl-2/Bax protein ratio, and increased protein expression of Caspase-9/3. Moreover, emodin suppressed oxidative stress in Hcy-treated H9C2 cells. Mechanistically, emodin significantly inhibited the Hcy-activated MAPK by reducing ROS generation in H9C2 cells. Furthermore, emodin upregulated NO production by promoting the protein phosphorylation of Akt and eNOS in injured cells. The present study shows that emodin protects against Hcy-induced cardiac dysfunction by inhibiting oxidative stress via MAPK and Akt/eNOS/NO signaling pathways.

Prevalence of depression, anxiety in China during the COVID-19 pandemic: an updated systematic review and meta-analysis.

Background: Mental health risks associated with the aftermath of the COVID-19 pandemic are often overlooked by the public. The aim of this study was to investigate the effects of the COVID-19 pandemic on depression and anxiety disorders in China. Methods: Studies were analyzed and extracted in accordance with the PRISMA 2020 flowchart. The studies were screened and extracted using electronic databases including PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov according to the predefined eligibility criteria. The Cochrane Review Manager software 5.3.1 was used for data analysis and the risk of bias assessment. Results: As of 2023, a total of 9,212,751 Chinese have been diagnosed with COVID-19 infection. A total of 913,036 participants in 44 studies were selected following the eligibility criteria, the statistical information of which was collected for meta-analysis. The pooled prevalence of depression and anxiety were 0.31 (95% CI: 0.28, 0.35; I2 = 100.0%, p < 0.001) and 0.29 (95% CI: 0.23, 0.36; I2 = 100.0%, p < 0.001), respectively. After performing a subgroup analysis, the prevalence of depression among women, healthcare workers, students, and adolescents was 0.31 (95% CI: 0.22, 0.41), 0.33 (95% CI: 0.26, 0.44), 0.32 (95% CI: 0.26, 0.39), and 0.37 (95% CI: 0.31, 0.44), respectively. Conclusion: The prevalence of depression and anxiety among the Chinese was overall high. Monitoring and surveillance of the mental health status of the population during crises such as sudden global pandemics are imperative. Systematic review registration: https://clinicaltrials.gov/, identifier [CRD42023402190].

Identification of adaptor proteins using the ANOVA feature selection technique.

The adaptor proteins play a crucially important role in regulating lymphocyte activation. Rapid and efficient identification of adaptor proteins is essential for understanding their functions. However, biochemical methods require not only expensive experimental costs, but also long experiment cycles and more personnel. Therefore, a computational method that could accurately identify adaptor proteins is urgently needed. To solve this issue, we developed a classifier that combined the support vector machine (SVM) with the composition of k-Spaced Amino Acid Pairs (CKSAAP) and the amino acid composition (AAC) to identify adaptor proteins. Analysis of variance (ANOVA) was used to select the optimized features which could generate the maximum prediction performance. By examining the proposed model on independent data, we found that the 447 optimized features could achieve an accuracy of 92.39% with an AUC of 0.9766, demonstrating the powerful capabilities of our model. We hope that the proposed model could provide more clues for studying adaptor proteins.

The crosstalk between macrophages and bone marrow mesenchymal stem cells in bone healing.

Bone injury plagues millions of patients worldwide every year, and it demands a heavy portion of expense from the public medical insurance system. At present, orthopedists think that autologous bone transplantation is the gold standard for treating large-scale bone defects. However, this method has significant limitations, which means that parts of patients cannot obtain a satisfactory prognosis. Therefore, a basic study on new therapeutic methods is urgently needed. The in-depth research on crosstalk between macrophages (Mϕs) and bone marrow mesenchymal stem cells (BMSCs) suggests that there is a close relationship between inflammation and regeneration. The in-depth understanding of the crosstalk between Mϕs and BMSCs is helpful to amplify the efficacy of stem cell-based treatment for bone injury. Only in the suitable inflammatory microenvironment can the damaged tissues containing stem cells obtain satisfactory healing outcomes. The excessive tissue inflammation and lack of stem cells make the transplantation of biomaterials necessary. We can expect that the crosstalk between Mϕs and BMSCs and biomaterials will become the mainstream to explore new methods for bone injury in the future. This review mainly summarizes the research on the crosstalk between Mϕs and BMSCs and also briefly describes the effects of biomaterials and aging on cell transplantation therapy.

An Ultrahigh Linear Sensitive Temperature Sensor Based on PANI:Graphene and PDMS Hybrid with Negative Temperature Compensation.

The detection of human body temperature is one of the important indicators to reflect the physical condition. In order to accurately judge the state of the human body, a high-performance temperature sensor with fast response, high sensitivity, and good linearity characteristics is urgently needed. In this paper, the positive temperature characteristics of graphene-polydimethylsiloxane (PDMS) composite with high sensitivity were studied. Besides, doping polyaniline (PANI) with special negative temperature characteristics as the temperature compensation of the composite finally creatively solved the problem of sensor nonlinearity from the material level. Thus, the PANI:graphene and PDMS hybrid temperature sensor with extraordinary linearity and high sensitivity is realized by establishing the space-gap model and mathematical theoretical analysis. The prepared sensor exhibits high sensitivity (1.60%/°C), linearity (R2 = 0.99), accuracy (0.3 °C), and time response (0.7 s) in the temperature sensing range of 25-40 °C. Based on this, the fabricated temperature sensor can combine with the read-out circuit and filter circuit with a high-precision analog digital converter (ADC) to monitor real-time skin temperature, ambient temperature, and respiratory rate, et al. This high-performance temperature sensor reveals its great potential in electronic skin, disease diagnosis, medical monitoring, and other fields.

MiR-214-3p Prevents the Development of Perioperative Neurocognitive Disorders in Elderly Rats.

OBJECTIVE: This study aimed to identify microRNAs (miRNAs) involved in the development of perioperative neurocognitive disorders (PND). METHODS: Plasma exosomal miRNA expression was examined in patients before and after cardiopulmonary bypass (CPB) using microarray and qRT-PCR and these patients were diagnosed as PND later. Elderly rats were subjected to CPB, and the cognitive functions were examined. Bioinformatics analysis was conducted to predict the targets of miR-214-3p. Rats were administered rno-miR-214-3p agomir before or after CPB to investigate the role of miR-214-3p in PND development. RESULTS: We identified 76 differentially expressed plasma exosomal miRNAs in PND patients after surgery (P<0.05, ∣log2FC∣>0.58), including the upregulated hsa-miR-214-3p (P=0.002399392). Prostaglandin-endoperoxide synthase 2 (PTGS2) was predicted as a miR-214-3p target. In rats, CPB reduced the platform crossing numbers and target quadrant stay time, accompanied with hippocampal neuronal necrosis. The rno-miR-214-3p level was significantly increased in plasma exosomes but decreased in rat hippocampus after surgery, exhibiting a negative correlation (P<0.001, r=-0.762). A negative correlation between miR-214-3p and PTGS2 protein expression was also observed in the hippocampus after surgery. Importantly, rno-miR-214-3p agomir treatment, before or after surgery, significantly increased the platform crossing numbers (P=0.035) and target quadrant stay time (P=0.029) compared with negative control. Hippocampal PTGS2 protein level was increased in the untreated surgery group and decreased in response to rno-miR-214-3p agomir treatment before or after surgery (both P<0.05 vs. negative control). CONCLUSION: These data suggest that miR-214-3p/PTGS2 signaling contributes to the development of PND, serving as a potential therapeutic target for PND.

Decreased gene expression of KACh and KATP channels in hyperthyroid rabbit atria.

Cardiac hypertrophy is a common myocardial structural abnormality which may cause heart failure. Many studies have shown that cardiac hypertrophy can be induced by hyperthyroidism. Ligand-gated potassium channels have been reported to be involved in various biological processes in the cardiovascular system, such as GPCR coupled KACh and metabolism sensor KATP channel. It is unclear whether the gene expression of KACh and KATP was altered in hyperthyroid rabbit atria. We aimed to investigate the expression of KACh and KATP genes in rabbit atria in our experimental model. We established an effective hyperthyroidism-induced cardiac hypertrophy animal model through an injection of T4. H&E staining and RT-PCR were used to observe the histomorphological damages and alteration of gene expression. The results showed that the heart weight, heart rate significantly increased in T4-treated rabbits. The systolic pressure increased from 115.60 mmHg to 152.6 mmHg in T4-treated rabbits. The expression of KACh and KATP genes was decreased in the atria of hyperthyroidism-induced cardiac hypertrophied rabbits. These findings indicated that the decreased gene expression of KACh and KATP may be related to hyperthyroidism-induced cardiac hypertrophy and atrial fibrillation.