Isoporous Membrane Mediated Imprinting Mass Spectrometry Imaging for Spatially-Resolved Metabolomics and Rapid Histopathological Diagnosis.

Surface-assisted laser desorption/ionization (SALDI) mass spectrometry imaging (MSI) holds great value in spatial metabolomics and tumor diagnosis. Tissue imprinting on the SALDI target can avoid laser-induced tissue ablation and simplifies the sample preparation. However, the tissue imprinting process always causes lateral diffusion of biomolecules, thereby losing the fidelity of metabolite distribution on tissue. Herein, a membrane-mediated imprinting mass spectrometry imaging (MMI-MSI) strategy is proposed using isoporous nuclepore track-etched membrane as a mediating imprinting layer to selectively transport metabolites through uniform and vertical pores onto silicon nanowires (SiNWs) array. Compared with conventional direct imprinting technique, MMI-MSI can not only exclude the adsorption of large biomolecules but also avoid the lateral diffusion of metabolites. The whole time for MMI-based sample preparation can be reduced to 2 min, and the lipid peak number can increase from 46 to 113 in kidney tissue detection. Meanwhile, higher resolution of MSI can be achieved due to the confinement effect of the pore channel in the diffusion of metabolites. Based on MMI-MSI, the tumor margins of liver cancer can be clearly discriminated and their different subtypes can be precisely classified. This work demonstrates MMI-MSI is a rapid, highly sensitive, robust and high-resolution technique for spatially-resolved metabolomics and pathological diagnosis.

An Intense Out-of-Season Rebound of Influenza Activity After the Relaxation of Coronavirus Disease 2019 Restrictions in Beijing, China.

Background: The aim of this study was to investigate the changes of epidemic characteristics of influenza activity pre- and post-coronavirus disease 2019 (COVID-19) in Beijing, China. Methods: Epidemiologic data were collected from the influenza surveillance system in Beijing. We compared epidemic intensity, epidemic onset and duration, and influenza transmissibility during the 2022-2023 season with pre-COVID-19 seasons from 2014 to 2020. Results: The overall incidence rate of influenza in the 2022-2023 season was significantly higher than that of the pre-COVID-19 period, with the record-high level of epidemic intensity in Beijing. The onset and duration of the influenza epidemic period in 2022-2023 season was notably later and shorter than that of the 2014-2020 seasons. Maximum daily instantaneous reproduction number (Rt) of the 2022-2023 season (Rt = 2.31) was much higher than that of the pre-COVID-19 period (Rt = 1.49). The incidence of influenza A(H1N1) and A(H3N2) were the highest among children aged 0-4 years and 5-14 years, respectively, in the 2022-2023 season. Conclusions: A late, intense, and short-term peak influenza activity was observed in the 2022-2023 season in Beijing. Children <15 years old were impacted the most by the interruption of influenza circulation during the COVID-19 pandemic. Maintaining continuous surveillance and developing targeted public health strategies of influenza is necessary.

Design and analysis of a complementary structure-based high selectivity tri-band frequency selective surface.

This work presents a novel tri-band bandpass frequency selective surface (FSS) that achieves high-order filtering responses in different frequency bands by means of a complementary structure. The proposed FSS is composed of three metal periodic arrays, which are separated by multilayer dielectric substrates. The gridded-double convoluted loop (G-DCL) structure, which is the middle layer structure, is a hybrid resonator that generates different resonant frequencies. The top and bottom layer structures are designed as complementary structures to the middle layer. To accurately describe the frequency responses, an equivalent circuit model (ECM) has been constructed over the entire band from 0 to 16 GHz. The results of the simulation indicate that the developed FSS can generate three pass-bands operating at 3.79 GHz, 8.34 GHz, and 12.52 GHz, respectively, and - 3 dB fractional bandwidths are 52.8%, 13.7%, and 19.7%. The transmission responses at the edges of each passband show a quick roll-off from the passband to the stopband, and there is significant out-of-band suppression between adjacent passbands. Moreover, the FSS maintains excellent angular and polarization stability within a 50° range. For verification, the tri-band FSS has been fabricated and tested. The experimental results match the simulation results, validating the accuracy of the FSS design.

Development of an efficient liposomal DOX delivery formulation for HCC therapy by targeting CK2α.

Hepatocellular carcinoma (HCC) is a digestive tract cancer with high mortality and poor prognosis, especially in China. Current chemotherapeutic drugs lead to poor prognosis, low efficacy, and high side effects due to weak targeting specificity and rapidly formed multidrug resistance (MDR). Based on the previous studies on the doxorubicin (DOX) formulation for cancer targeting therapy, we developed a novel DOX delivery formulation for the targeting chemotherapy of HCC and DOX resistant HCC. HCSP4 was previously screened and casein kinase 2α (CK2α) was predicted as its specific target on HCC cells in our lab. In the study, miR125a-5p was firstly predicted as an MDR inhibiting miRNA, and then CK2α was validated as the target of HCSP4 and miR125a-5p using CK2α-/-HepG2 cells. Based on the above, an HCC targeting and MDR inhibiting DOX delivery liposomal formulation, HCSP4/Lipo-DOX/miR125a-5p was synthesized and tested for its HCC therapeutic efficacy in vitro. The results showed that the liposomal DOX delivery formulation targeted to HCC cells specifically and sensitively, and presented the satisfied therapeutic efficacy for HCC, particularly for DOX resistant HCC. The potential therapeutic mechanism of the DOX delivery formulation was explored, and the formulation inhibited the expression of MDR-relevant genes including ATP-binding cassette subfamily B member 1 (ABCB1, also known as P-glycoprotein), ATP-binding cassette subfamily C member 5 (ABCC5), enhancer of zeste homolog 2 (EZH2), and ATPase Na+/K+ transporting subunit beta 1 (ATP1B1). Our study presents a novel targeting chemotherapeutic drug formulation for the therapy of HCC, especially for drug resistant HCC, although it is primarily and needs further study in vivo, but provided a new strategy for the development of novel anticancer drugs.

How to assess the long-term recovery outcomes of patients with cauda equina syndrome before surgery: a retrospective cohort study.

BACKGROUND: Factors influencing recovery after decompression surgery for cauda equina syndrome (CES) are not completely identified. We aimed to investigate the most valuable predictors (MVPs) of poor postoperative recovery (PPR) in patients with CES and construct a nomogram for discerning those who will experience PPR. METHODS: 356 patients with CES secondary to lumbar degenerative diseases treated at *** Hospital were randomly divided into training (N=238) and validation (N=118) cohorts at a 2:1 ratio. Moreover, 92 patients from the **** Hospital composed the testing cohort. Least Absolute Shrinkage and Selection Operator regression (LASSO) was used for selecting MVPs. The nomogram was developed by integrating coefficients of MVPs in the logistic regression, and its discrimination, calibration, and clinical utility were validated in all three cohorts. RESULTS: After 3 to 5 years of follow-up, the residual rates of bladder dysfunction, bowel dysfunction, sexual dysfunction, and saddle anesthesia were 41.9%, 44.1%, 63.7%, and 29.0%, respectively. MVPs included stress urinary incontinence, overactive bladder, low stream, difficult defecation, fecal incontinence, and saddle anesthesia in order. The discriminatory ability of the nomogram was up to 0.896, 0.919, and 0.848 in the training, validation, and testing cohorts, respectively. Besides, the nomogram showed good calibration and clinical utility in all cohorts. Furthermore, the optimal cut-off value of the nomogram score for distinguishing those who will experience PPR was 148.02, above which postoperative outcomes tend to be poor. CONCLUSION: The first pre-treatment nomogram for discerning CES patients who will experience PPR was developed and validated, which will aid clinicians in clinical decision-making.

Far-red light modulates grapevine growth by increasing leaf photosynthesis efficiency and triggering organ-specific transcriptome remodelling : Author.

BACKGROUND: Growing evidence demonstrates that the synergistic interaction of far-red light with shorter wavelength lights could evidently improve the photosynthesis efficiency of multiple species. However, whether/how far-red light affects sink organs and consequently modulates the source‒sink relationships are largely unknown. RESULTS: Here, equal intensities of white and far-red lights were added to natural light for grape plantlets to investigate the effects of far-red light supplementation on grapevine growth and carbon assimilate allocation, as well as to reveal the underlying mechanisms, through physiological and transcriptomic analysis. The results showed that additional far-red light increased stem length and carbohydrate contents in multiple organs and decreased leaf area, specific leaf weight and dry weight of leaves in comparison with their counterparts grown under white light. Compared to white light, the maximum net photosynthetic rate of the leaves was increased by 31.72% by far-red light supplementation, indicating that far-red light indeed elevated the photosynthesis efficiency of grapes. Transcriptome analysis revealed that leaves were most responsive to far-red light, followed by sink organs, including stems and roots. Genes related to light signaling and carbon metabolites were tightly correlated with variations in the aforementioned physiological traits. In particular, VvLHCB1 is involved in light harvesting and restoring the balance of photosystem I and photosystem II excitation, and VvCOP1 and VvPIF3, which regulate light signal transduction, were upregulated under far-red conditions. In addition, the transcript abundances of the sugar transporter-encoding genes VvSWEET1 and VvSWEET3 and the carbon metabolite-encoding genes VvG6PD, VvSUS7 and VvPGAM varied in line with the change in sugar content. CONCLUSIONS: This study showed that far-red light synergistically functioning with white light has a beneficial effect on grape photosystem activity and is able to differentially affect the growth of sink organs, providing evidence for the possible addition of far-red light to the wavelength range of photosynthetically active radiation (PAR).

Feline Adult Adipose Tissue-Derived Multipotent Stromal Cell Isolation and Differentiation.

Cats are among the most popular household pets. However, compared to other species, there is little information specific to feline adult mesenchymal stromal/stem cells. Despite the phylogenetic distance between domesticated cats, Felis silvestris catus, and humans, they share some similar health challenges like kidney disease, asthma, and diabetes. Investigative efforts have been focused on adult adipose-derived stromal/stem cell (ASC) therapies to address feline illnesses, including de novo pancreatic tissue generation for diabetes treatment. Given the relatively small size of domestic cats, optimized cell isolation from small quantities of adipose tissue is important in the development of feline ASC-based therapies. Additionally, there are unique features of feline ASC culture conditions and characterization. This chapter contains a few of the novel aspects of feline ASC isolation, culture, preservation, and differentiation.

Understanding the variable metal concentrations in estuarine oysters Crassostrea hongkongensis: A biokinetic analysis.

Understanding the metal concentrations in oysters is important because of its relevance to human health and biomonitoring. However, metal concentrations in oysters are highly variable in nature and not well explained by metal exposure. This study examined the metal contamination in farm oysters Crassostrea hongkongensis grown in Qinzhou Bay, south China. Cadmium (Cd), zinc (Zn), nickel (Ni), and copper (Cu) concentrations in the oysters varied between 7.9 and 72.2, 282-17003, 0.37-47.7 and 37-4012 µg g-1, respectively, showing large metal variability among different individuals. Oyster metal concentrations decreased with increasing body size and significantly higher levels were observed in wet season. Low salinity and slower oyster growth due to inferior growth conditions could be responsible for the elevated metal concentrations in the wet season. Biokinetic modeling showed that the coupling of ingestion rate and growth can cause 2.8-4.2 folds differences in the oyster Cd and Zn concentrations, respectively, suggesting the significant role of oyster bioenergetics in contributing to the metal variability. Modeling data revealed that Cd and Zn concentrations in oyster tissues reach maximum levels when oysters have their lowest growth efficiency. This suggests that any factors influencing the energy budget in oysters could simultaneously alter their metal concentrations, which might be the reason why oyster metal concentrations are so variable in the natural environment.

Management of Venous Access Port to Overcome Kinesiophobia of Patients with Malignant Tumors: A Review.

The number of patients with malignant tumors is increasing in China, and venous access ports have unique advantages for chemotherapy. Currently, China's research on venous access port-mediated kinesiophobia is still in the developing stage. Using the combination of subjective words and freedom words, and based on literature traceability methods, China National Knowledge Infrastructure (CNKI), Wanfang, Vipp, Chinese Biomedical Database (CBM), Web of Science, The COCHRANE LIBRARY, Embase, and PubMed were searched. Relevant articles published from the construction of the database to October 30, 2023, were identified. Based on the many articles and analyses, the methods of assessing kinesiophobia in malignant tumors patients using venous access port, the related influencing factors and the preventive and intervention strategies were collated. We found 33 articles examining kinesiophobia in oncology patients, of which 4 were specifically conducted on patients with malignant tumors using VAPs or PICCs. The relevant preventive and therapeutic experiences regarding kinesiophobia in cancer patients with VAP still need improvement. Nursing staff can use assessment tools such as the Tampa Rating Scale for Kinesiophobia, the Fear Avoidance Beliefs Questionnaire, and the Cancer Fatigue Scale to reasonably and effectively assess kinesiophobia among patients with malignant tumors who use VAPs. Attention should be paid to the mechanisms and roles of demographic factors, pain and foreign body sensation, cancer fatigue, pain management strategies, and other factors influencing kinesiophobia. This study provides advice to nursing staff for the management of VAP. Such considerations may reduce the complications of kinesiophobia and improve the quality of life of patients.

The effectiveness of online group mindfulness-based cognitive therapy for outpatients with depression in China.

OBJECTIVES: With the development of online technology and the increase in real-world needs, conducting psychotherapy on online platforms has become a popular trend. The present study followed the schedule and content of Mindfulness-based Cognitive Therapy (MBCT), and only changed the treatment format (from offline to online) to investigate the effectiveness of online group MBCT for Chinese outpatients with depression. METHODS: The study used before-and-after controlled design, and included 88 depressed outpatients, of which 75 formally underwent a 10-week online group MBCT. The 24-item Hamilton Depression Scale (HAMD-24), Hamilton Anxiety Scale (HAMA), Self-Depression Rating Scale (SDS), Mindful Attention Awareness Scale (MAAS), and Self-Acceptance Questionnaire (SAQ) were administered to patients one week prior to treatment, the fifth week of treatment, and the tenth week of treatment. Repeated-measures data were processed using linear mixed-effects models. RESULTS: 75 patients (85.23 %) attended >4 sessions, 44 of whom were taking psychotropic medication during treatment. HAMD-24 and HAMA scores decreased significantly in both medicated and unmedicated patients (w10 < w1, p < 0.05). HAMD-24 and HAMA scores declined more rapidly in patients taking medication, with significant decreases in the fifth week (w5 < w1, p < 0.05). The remarkable effectiveness of treatment (HAMD-24 score reduction >50 %) was >30 %, but there were no significant changes in patients' SDS, MAAS, or SAQ scores. CONCLUSIONS: This study supports the effectiveness of online group MBCT for outpatients with depression and the adherence of depressed patients to participate in online group MBCT was high.

Comparative effectiveness and safety of intravenous methylprednisolone and tacrolimus monotherapy in ocular myasthenia gravis with unsatisfactory prednisone responses: a retrospective study.

BACKGROUND: Oral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy. METHODS: We retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded. RESULTS: Both IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p = 0.002; 69.0% (20/29) vs 40.0% (10/25), p = 0.033; 69.0% (20/29) vs 46.4% (13/28), p = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066-2.975; p = 0.028). All the adverse events were transient and tolerable. CONCLUSION: Our findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.

An EEG motor imagery dataset for brain computer interface in acute stroke patients.

The brain-computer interface (BCI) is a technology that involves direct communication with parts of the brain and has evolved rapidly in recent years; it has begun to be used in clinical practice, such as for patient rehabilitation. Patient electroencephalography (EEG) datasets are critical for algorithm optimization and clinical applications of BCIs but are rare at present. We collected data from 50 acute stroke patients with wireless portable saline EEG devices during the performance of two tasks: 1) imagining right-handed movements and 2) imagining left-handed movements. The dataset consists of four types of data: 1) the motor imagery instructions, 2) raw recording data, 3) pre-processed data after removing artefacts and other manipulations, and 4) patient characteristics. This is the first open dataset to address left- and right-handed motor imagery in acute stroke patients. We believe that the dataset will be very helpful for analysing brain activation and designing decoding methods that are more applicable for acute stroke patients, which will greatly facilitate research in the field of motor imagery-BCI.

Computational markers of risky decision-making predict for relapse to alcohol.

BACKGROUND: Relapse remains the major challenge in treatment of alcohol use disorder (AUD). Aberrant decision-making has been found as important cognitive mechanism underlying relapse, but factors associated with relapse vulnerability are unclear. Here, we aim to identify potential computational markers of relapse vulnerability by investigating risky decision-making in individuals with AUD. METHODS: Forty-six healthy controls and fifty-two individuals with AUD were recruited for this study. The risk-taking propensity of these subjects was investigated using the balloon analog risk task (BART). After completion of clinical treatment, all individuals with AUD were followed up and divided into a non-relapse AUD group and a relapse AUD group according to their drinking status. RESULTS: The risk-taking propensity differed significantly among healthy controls, the non-relapse AUD group, and the relapse AUD group, and was negatively associated with the duration of abstinence in individuals with AUD. Logistic regression models showed that risk-taking propensity, as measured by the computational model, was a valid predictor of alcohol relapse, and higher risk-taking propensity was associated with greater risk of relapse to drink. CONCLUSION: Our study presents new insights into risk-taking measurement and identifies computational markers that provide prospective information for relapse to drink in individuals with AUD.

Integrating multi-level interactive network and in vivo/vitro studies to explore the protective mechanism of Ampelopsis grossedentata in hyperuricemia.

The strategies or drugs for preventing and treating Hyperuricemia (HUA) are still lacking. As a traditional Chinese medicine (TCM) with a profound history, Ampelopsis grossedentata has been shown to play diverse biological roles. The purpose of the present study was to evaluate hypouricemic effect of A. grossedentata, and investigate its involved material basis and mechanism. A HUA mice model was established to evaluate the therapeutic effects of A. grossedentata. And then some extracts from A. grossedentata were prepared, isolated and analyzed. Furthermore, network pharmacology, based on the above results, was used to discover potential active ingredients and therapeutic targets, and they were further verified and explored by molecular docking and in vitro experiments. In vivo experiments showed that A. grossedentata exerted hypouricemic effect on mice of HUA. The core active ingredients (quercetin, myricetin and dihydromyricetin etc.) and core targets (PTGS2, XOD and ABCG2 etc.) for A. grossedentata to treat HUA were predicted by network pharmacology. And molecular docking showed that the spontaneous binding activities of above components and targets were marvelous. In vitro experiments further demonstrated that A. grossedentata exerted hypouricemic effect by decreasing the levels of UA, XOD, antioxidant factors, inflammatory factors, GLUT9 and URAT1 in HK-2 cells of HUA. Taken together, this study integrates multi-level interaction network with in vivo/vitro experiments to systematically reveal the material basis and mechanism of A. grossedentata in treating HUA, which provides a scientific basis for further study of A. grossedentata and HUA.

The Genome of Vitis zhejiang-adstricta Strengthens the Protection and Utilization of the Endangered Ancient Grape Endemic to China.

Vitis zhejiang-adstricta (V. zhejiang-adstricta) is one of the most important and endangered wild grapes. It is a national key protected wild, rare and endangered ancient grape endemic to China and used as a candidate material for resistance breeding owing to its excellent significant disease resistance. Here, we present a high-quality chromosome-level assembly of V. zhejiang-adstricta (IB-VB-01), comprising 506.66 Mb assembled into 19 pseudo-chromosomes. The contig N50 length is 3.91 Mb with 31,196 annotated protein-coding genes. Comparative genome and evolutionary analyses illustrated that V. zhejiang-adstricta has a specific position in the evolution of East Asian Vitis and shared a common ancestor with Vitis vinifera during the divergence of the two species about 10.42 (between 9.34 and 11.12) Mya. The expanded gene families compared with those in plants were related to disease resistance, and constructed gene families were related to plant growth and primary metabolism. With the analysis of gene family expansion and contraction, the evolution of environmental adaptability and especially the NBS-LRR gene family of V. zhejiang-adstricta was elucidated based on the pathways of resistance genes (R genes), unique genes and structural variations. The near-complete and accurate diploid V. zhejiang-adstricta reference genome obtained herein serves as an important complement to wild grape genomes and will provide valuable genomic resources for investigating the genomic architecture of V. zhejiang-adstricta as well as for improving disease resistance breeding strategies in grape.

The role of absolute humidity in influenza transmission in Beijing, China: risk assessment and attributable fraction identification.

To assess the impact of absolute humidity on influenza transmission in Beijing from 2014 to 2019, we estimated the influenza transmissibility via the instantaneous reproduction number (Rt), and evaluated its nonlinear exposure-response association and delayed effects with absolute humidity by using the distributed lag nonlinear model (DLNM). Attributable fraction (AF) of Rt due to absolute humidity was calculated. The result showed a significant M-shaped relationship between Rt and absolute humidity. Compared with the effect of high absolute humidity, the low absolute humidity effect was more immediate with the most significant effect observed at lag 6 days. AFs were relatively high for the group aged 15-24 years, and was the lowest for the group aged 0-4 years with low absolute humidity. Therefore, we concluded that the component attributed to the low absolute humidity effect is greater. Young and middle-aged people are more sensitive to low absolute humidity than children and elderly.

Polychromatic Dual-Mode Imaging with Structured Chiral Photonic Crystals.

Optical spatial differentiation is a typical operation of optical analog computing and can single out the edge to accelerate the subsequent image processing, but in some cases, overall information about the object needs to be presented synchronously. Here, we propose a multifunctional optical device based on structured chiral photonic crystals for the simultaneous realization of real-time dual-mode imaging. This optical differentiator is realized by self-organized large-birefringence cholesteric liquid crystals, which are photopatterned to encode with a special integrated geometric phase. Two highly spin-selective modes of second-order spatial differentiation and bright-field imaging are exhibited in the reflected and transmitted directions, respectively. Two-dimensional edges of both amplitude and phase objects have been efficiently enhanced in high contrast and the broadband spectrum. This work extends the ingenious building of hierarchical chiral nanostructures, enriches their applications in the emerging frontiers of optical computing, and boasts considerable potential in machine vision and microscopy.

Imaging mRNA in vitro and in vivo with nanofirecracker probes via intramolecular hybridization chain reaction.

Hybridization chain reaction (HCR) based enzyme-free amplification techniques have recently been developed for the visualization of intracellular messenger RNA (mRNA). However, the slow kinetics and potential interference with the intricate biological environments hinder its application in the clinic and in vivo. Herein, we designed a nanofirecracker probe-based strategy using intramolecular hybridization chain reaction (IHCR) amplifier for rapid, efficient, sensitive, specific detection and imaging of survivin mRNA both in vitro and vivo. Two probes, HP1 and HP2, in IHCR were simultaneously incorporated into a DNA nanowire scaffolds to bring HP1 and HP2 to close proximity on the assembled nanowire scaffolds. Empowered by the DNA nanowire scaffolds and spatial confinement effect, the nanofirecracker probe-based IHCR sensing system exhibited improved biostability, accelerated reaction kinetics, and enhanced signal amplification. This new strategy has been successfully applied to imaging mRNA in both cultured cells and in mice. Importantly, this novel sensing method was capable of detecting survivin mRNA in clinical blood samples from subjects with colorectal cancer. Thus, this novel nanofirecracker probe-based IHCR strategy holds great potential in advancing both biomedical research and in molecular diagnostics.

miR-22-3p in the rostral ventrolateral medulla promotes hypertension through inhibiting ß-arrestin-1.

It has been documented that increased sympathetic activity contributes to the development of cardiovascular diseases, such as hypertension. We previously reported that ß-arrestin-1, a multifunctional cytoskeletal protein, was downregulated in the rostral ventrolateral medulla (RVLM) of the spontaneously hypertensive rat (SHR), and its overexpression elicited an inhibitory effect on sympathetic activity in hypertension. microRNA (miR)-22-3p has been reported to be associated with the pathological progress of hypertension. The purpose of this study was to determine the role of miR-22-3p in ß-arrestin-1-mediated central cardiovascular regulation in hypertension. It was observed that miR-22-3p was upregulated in the RVLM of SHRs compared with normotensive Wistar-Kyoto (WKY) rats, and it was subsequently confirmed to target the ß-arrestin-1 gene using a dual-luciferase reporter assay. miR-22-3p was downregulated in the RVLM using adeno-associated virus with 'tough decoys', which caused a significant increase of ß-arrestin-1 expression and decrease of noradrenaline and blood pressure (BP) in SHRs. However, upregulation of miR-22-3p using lentivirus in the RVLM of WKY rats significantly increased BP. In in vitro PC12 cells, enhanced oxidative stress activity induced by angiotensin II was counteracted by pretreatment with miR-22-3p inhibitor, and this effect could be abolished by ß-arrestin-1 gene knockdown. Furthermore, microglia exhaustion significantly diminished miR-22-3p expression, and enhanced ß-arrestin-1 expression in the RVLM of SHRs. Activation of BV2 cells in vitro evoked a significant increase of miR-22-3p expression, and this BV2 cell culture medium was also able to facilitate miR-22-3p expression in PC12 cells. Collectively, our findings support a critical role for microglia-derived miR-22-3p in inhibiting ß-arrestin-1 in the RVLM, which is involved in central cardiovascular regulation in hypertension. KEY POINTS: Impairment of ß-arrestin-1 function in the rostral ventrolateral medulla (RVLM) has been reported to be associated with the development of sympathetic overactivity in hypertension. However, little is known about the potential mechanisms of ß-arrestin-1 dysfunction in hypertension. miR-22-3p is implicated in multiple biological processes, but the role of miR-22-3p in central regulation of cardiovascular activity in hypertension remains unknown. We predicted that miR-22-3p could directly bind to the ß-arrestin-1 gene (Arrb1), and this hypothesis was confirmed by using a dual-luciferase reporter assay. Inhibition of ß-arrestin-1 by miR-22-3p was further verified in both in vivo and in vitro experiments. Furthermore, our results suggested miR-22-3p as a risk factor for oxidative stress in the RVLM, thus contributing to sympatho-excitation and hypertension. Our present study provides evidence that microglia-derived miR-22-3p may underlie the pathogenesis and progression of neuronal hypertension by inhibiting ß-arrestin-1 in the RVLM.

A Novel System for Transcatheter Aortic Valve Implantation: First-in-Man Study.

Transcatheter aortic valve implantation (TAVI) has become a therapeutic treatment for severe symptomatic patients with aortic stenosis. This study aimed to test a novel transcatheter aortic self-expandable bioprosthesis-the ScienCrown system (Lepu Medtech Inc., Beijing, China)-and evaluate the safety of the new device during TAVI. ScienCrown aortic valve implantation was performed on 10 patients. Clinical assessment was performed at baseline, post procedure, and after 1 year. Clinical outcomes and adverse events were assessed according to Valvular Academic Research Consortium-3 criteria. The mean age was 75.30 ± 4.78 years with a mean Society of Thoracic Surgeons score of 4.64 ± 3.23%. Device success was achieved in all patients (80% transfemoral, 20% transapical). After 1 year, there were no deaths, disabling strokes, myocardial infarctions, conversions to surgery, or major procedure-related complications. New pacemaker implantation was required in one patient (10%). ScienCrown implantation resulted in a reduction in mean valve gradient (63.00 ± 18.84 to 9.67 ± 4.97 mm Hg, p <0.001) and an increase in effective orifice area (0.57 ± 0.20 to 2.57 ± 0.59 cm2, p <0.001) at 1 year. Paravalvular leak was absent in 9 patients (90%), and there was a trace in one patient (10%). All patients were in New York Heart Association class I to II at a mean follow-up of 1 year. The experience showed that ScienCrown transcatheter aortic valve system was safely and successfully implanted for treatment of severe symptomatic aortic stenosis. The newer-generation device affords a stable implantation while providing optimal hemodynamic performance.