Identification of genetic susceptibility in preterm newborns with bronchopulmonary dysplasia by whole-exome sequencing: BIVM gene may play a role.

Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in preterm infants caused by multifactorial etiology. Genetic factors are involved in the occurrence of BPD, but studies have found that candidate genes have poor reproducibility and are influenced by ethnic heterogeneity; therefore, more exploration is still needed. We performed whole-exon sequencing in 34 preterm infants with BPD and 32 non-BPD control neonates. The data were analyzed and interpreted by Fisher difference comparison, PLINK and eQTL association analysis, KEGG and GO enrichment analysis, STRING tool, Cytoscape software, ProtParam tool, HOPE online software, and GEOR2 analysis on NCBI GEO dataset. BPD has a highly heterogeneity in different populations, and we found 35 genes overlapped with previous whole-exon sequencing studies, such as APOB gene. Arterial and epithelial cell development and energy metabolism pathways affect BPD. In this study, 24 key genes were identified, and BIVM rs3825519 mutation leads to prolonged assisted ventilation in patients with BPD. A novel DDAH1 mutation site (NM_012137: exon1: c.89 T > G: p.L30R) was found in 9 BPD patients. CONCLUSION: BIVM gene rs3825519 mutation may play a role in the pathogenesis of BPD by affecting cilia movement, and the DDAH1 and APOB genes mutations may have a pathogenic role in BPD. WHAT IS KNOWN: • Genetic factors are involved in the occurrence of bronchopulmonary dysplasia. • The candidate genes have poor reproducibility and are influenced by ethnic heterogeneity, therefore, more exploration is still needed. WHAT IS NEW: • We identified the role of susceptible SNPs in BPD in Shenzhen, China, and identified 24 key genes that influence the pathogenesis of BPD, and also found 35 genes overlapped with previous whole exon sequencing studies, such as APOB gene. • We found that BIVM and DDAH1 genes may play a pathogenic role in the pathogenesis of BPD.

Effective Tools for the Metal-Catalyzed Regiodivergent Direct Arylations of (Hetero)arenes.

The direct functionalization of two different C-H bonds of the same organic molecule using different procedures - also called regiodivergent C-H bond functionalization - currently represents an important research topic in organic chemistry, as it demonstrates the versatility of C-H bond functionalization methodology. Over the last decade, the number of tools to control such regiodivergent C-H bond functionalizations has increased significantly. In this account, we will present the various tools that allowed us to arylate different positions of various (hetero)arenes, via a C-H bond functionalization, using palladium or ruthenium catalysis.

Therapeutic efficacy and cardioprotection of nucleolin-targeted doxorubicin-loaded ultrasound nanobubbles in treating triple-negative breast cancer.

Targeted lipid nanobubbles as theranostic ultrasound molecular probes with both targeted contrast-enhanced ultrasound molecular imaging and synergistic treatment capabilities are expected to overcome severe challenges in the diagnosis and treatment of refractory triple-negative breast cancer (TNBC). In this study, AS1411 aptamer-functionalised nucleolin-targeted doxorubicin-loaded lipid nanobubbles (AS1411-DOX-NBs) were constructed, and their physicochemical properties as well as anti-tumour and cardioprotective efficacies were systematically tested and evaluated. The results showed that AS1411-DOX-NBs can carry and maintain the physicochemical and pharmacodynamic properties of doxorubicin (DOX) and show stronger tumour cell-killing abilityin vitroby increasing the active uptake of drugs. AS1411-DOX-NBs also significantly inhibited the growth of TNBC xenografts while maintaining the weight and health of the mice. Echocardiography and pathological examination further confirmed that AS1411-DOX-NBs effectively caused tumour tissue apoptosis and necrosis while reducing DOX-induced cardiotoxicity. The AS1411-DOX-NBs constructed in this study enable both targeted contrast-enhanced ultrasound molecular imaging and synergistic therapeutic efficacy and can be used as safe and efficient theranostic ultrasound molecular probes for the diagnosis and treatment of TNBC.

Prognosis for patients with cognitive motor dissociation identified by brain-computer interface.

Cognitive motor dissociation describes a subset of patients with disorders of consciousness who show neuroimaging evidence of consciousness but no detectable command-following behaviours. Although essential for family counselling, decision-making, and the design of rehabilitation programmes, the prognosis for patients with cognitive motor dissociation remains under-investigated. The current study included 78 patients with disorders of consciousness who showed no detectable command-following behaviours. These patients included 45 patients with unresponsive wakefulness syndrome and 33 patients in a minimally conscious state, as diagnosed using the Coma Recovery Scale-Revised. Each patient underwent an EEG-based brain-computer interface experiment, in which he or she was instructed to perform an item-selection task (i.e. select a photograph or a number from two candidates). Patients who achieved statistically significant brain-computer interface accuracies were identified as cognitive motor dissociation. Two evaluations using the Coma Recovery Scale-Revised, one before the experiment and the other 3 months later, were carried out to measure the patients' behavioural improvements. Among the 78 patients with disorders of consciousness, our results showed that within the unresponsive wakefulness syndrome patient group, 15 of 18 patients with cognitive motor dissociation (83.33%) regained consciousness, while only five of the other 27 unresponsive wakefulness syndrome patients without significant brain-computer interface accuracies (18.52%) regained consciousness. Furthermore, within the minimally conscious state patient group, 14 of 16 patients with cognitive motor dissociation (87.5%) showed improvements in their Coma Recovery Scale-Revised scores, whereas only four of the other 17 minimally conscious state patients without significant brain-computer interface accuracies (23.53%) had improved Coma Recovery Scale-Revised scores. Our results suggest that patients with cognitive motor dissociation have a better outcome than other patients. Our findings extend current knowledge of the prognosis for patients with cognitive motor dissociation and have important implications for brain-computer interface-based clinical diagnosis and prognosis for patients with disorders of consciousness.

Alveolar ridge preservation with fibroblast growth factor-2 modified acellular dermal matrix membrane and a bovine-derived xenograft: An experimental in vivo study.

OBJECTIVE: To investigate the effect of a bone substitute material combined with fibroblast growth factor-2 (FGF-2) loaded barrier membrane on the preservation of alveolar ridge after tooth extraction. MATERIAL AND METHODS: Four dogs were included. Six extraction sockets of each animal received the 3 treatments and were randomly divided into three groups. Group A: negative control; Group B: bovine xenografts + membrane; and Group C: bovine xenografts + FGF-2-loaded membrane. CBCT and histological analysis were performed to evaluate changes in the width and height of alveolar ridges and extraction socket bone healing 8 weeks post-extraction. RESULTS: CBCT showed that the alveolar bone in Group A was significantly thinner than that in Group B and Group C at 1 and 3 mm apically from the alveolar crest. The alveolar width at 1 mm in Group C (60.99 ± 15.36%) was significantly thicker than that in Group B (39.75 ± 30.18%). Histomorphmetrical measurements showed that the buccal alveolar width at 1 mm was significantly thicker in Groups B and C than in Group A. Additionally, buccal bone height and lingual bone width at 1 mm in Group C (87.06 ± 10.34%, 89.09 ± 10.56%) were significantly greater than in Group A (53.48 ± 23.94%, 82.72 ± 12.59%). CONCLUSION: The present findings indicate that application of bovine bone combined with barrier membrane with or without FGF-2 over tooth sockets can effectively reduce ridge absorption, especially in terms of ridge width and FGF-2 modified membrane seems to improve the outcomes obtained with membrane alone.

LncRNA small nucleolar RNA host gene 16 (SNHG16) silencing protects lipopolysaccharide (LPS)-induced cell injury in human lung fibroblasts WI-38 through acting as miR-141-3p sponge.

Long noncoding RNA (LncRNA) small nucleolar RNA host gene 16 (SNHG16) is correlated with cell injuries, including pneumonia. However, its role and mechanism remain vague in pneumonia. The interplay among genes was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay. SNHG16 and sushi domain containing 2 (SUSD2) were upregulated, and miRNA (miR)-141-3p was downregulated in the serum of acute pneumonia patients and lipopolysaccharide (LPS)-challenged human lung fibroblasts WI-38. LPS induced apoptosis, autophagy, and inflammatory response in WI-38 cells, which was significantly attenuated by SNHG16 knockdown and/or miR-141-3p overexpression. Notably, both SNHG16 and SUSD2 were identified as target genes of miR-141-3p. Besides, the suppressive role of SNHG16 knockdown in LPS-induced in WI-38 cells was partially abolished by miR-141-3p silencing, and the similar inhibition of miR-141-3p overexpression was further blocked by SUSD2 restoration. In conclusion, knockdown of SNHG16 could alleviate LPS-induced apoptosis, autophagy, and inflammation in WI-38 cells partially though the SNHG16/miR-141-3p/SUSD2 pathway.

[An electroencephalogram-based study of resting-state spectrogram and attention in tinnitus patients].

The incidence of tinnitus is very high, which can affect the patient's attention, emotion and sleep, and even cause serious psychological distress and suicidal tendency. Currently, there is no uniform and objective method for tinnitus detection and therapy, and the mechanism of tinnitus is still unclear. In this study, we first collected the resting state electroencephalogram (EEG) data of tinnitus patients and healthy subjects. Then the power spectrum topology diagrams were compared of in the band of δ (0.5-3 Hz), θ (4-7 Hz), α (8-13 Hz), ß (14-30 Hz) and γ (31-50 Hz) to explore the central mechanism of tinnitus. A total of 16 tinnitus patients and 16 healthy subjects were recruited to participate in the experiment. The results of resting state EEG experiments found that the spectrum power value of tinnitus patients was higher than that of healthy subjects in all concerned frequency bands. The t-test results showed that the significant difference areas were mainly concentrated in the right temporal lobe of the θ and α band, and the temporal lobe, parietal lobe and forehead area of the ß and γ band. In addition, we designed an attention-related task experiment to further study the relationship between tinnitus and attention. The results showed that the classification accuracy of tinnitus patients was significantly lower than that of healthy subjects, and the highest classification accuracies were 80.21% and 88.75%, respectively. The experimental results indicate that tinnitus may cause the decrease of patients' attention.

Construction of Nucleolin-Targeted Lipid Nanobubbles and Contrast-Enhanced Ultrasound Molecular Imaging in Triple-Negative Breast Cancer.

PURPOSE: To construct aptamer AS1411-functionalized targeted lipid nanobubbles that could simultaneously target abnormally highly expressed nucleolin (NCL) on tumor tissue and neovasculature. Additionally, the study of their contrast-enhanced ultrasound molecular imaging capabilities in vitro and in vivo to explore new methods and approaches for the early and accurate diagnosis of triple-negative breast cancer (TNBC). METHODS: First, the targeted lipid-nucleic acid molecules were constructed by an amide reaction. Then, the targeted lipid nanobubbles (AS1411-NBs) and nontargeted lipid nanobubbles (NBs) were prepared by membrane hydration, mechanical vibration and centrifugal floatation. The physicochemical characteristics and contrast-enhanced ultrasound imaging capabilities of AS1411-NBs and NBs were compared and analyzed in vitro and in vivo. RESULTS: There were no significant differences between the AS1411-NBs and NBs in their concentration, average particle size or ultrasound imaging capabilities in vitro (P > 0.05). However, AS1411-NBs could simultaneously target NCL in tumor tissue and neovasculature to effectively prolong the duration of contrast-enhanced ultrasound imaging compared to NBs in vivo. The area under the time-intensity curve was significantly different between AS1411-NBs and NBs (P < 0.001), and the drug loading capacity of the AS1411-NBs was also significantly higher than that of the NBs (P < 0.05). CONCLUSIONS: Aptamer AS1411-functionalized targeted lipid nanobubbles could significantly prolong the duration of contrast-enhanced ultrasound imaging to achieve dual-targeted ultrasound molecular imaging of tumor tissue and neovasculature. AS1411-NBs also have higher drug loading and targeted drug delivery capabilities compared with NBs, which can provide new methods and approaches for the early accurate diagnosis and effective treatment of TNBC.

"One-stop shop": safety and efficacy of combining atrial septal defect occlusion and left atrial appendage closure for patients with atrial septal defect and atrial fibrillation.

BACKGROUND: One-stop occlusion, which is defined as the combination of atrial septal defect [ASD] or patent foramen ovale [PFO] occlusion and left atrial appendage [LAA] closure, in patients with ASD/PFO and atrial fibrillation (AF) has not yet been investigated systematically. This study aimed to evaluate the safety and efficacy of one-stop occlusion in the treatment of adult patients with ASD/PFO and AF. METHODS: Inpatients with AF and ASD/PFO were recruited between August 2014 and April 2019. Preoperatively, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were conducted to identify the ASD/PFO size and margin, presence of thrombus in the LAA, and LAA orifice width and depth at 0°, 45°, 90°, and 135°. After confirmation of the indications of LAA closure (LAAC) and ASD/PFO occlusion, the procedures were performed simultaneously under general anesthesia. Oral anticoagulants were administered for 45-60 days, followed with regular evaluation of TTE and TEE. RESULTS: Forty-nine patients (age, 65.6 ± 9.6 years) were recruited in this study, including 24 patients with ASD and 25 patients with PFO. They were treated with LAAC and ASD/PFO occlusion successfully. The mean ASD size and mean diameter of the ASD occluders were 14.2 ± 7.7 and 25.4 ± 8.5 mm, respectively. The mean PFO size was 3.5 ± 0.4 mm. The mean maximal LAA orifice width and depth were 20.5 ± 3.4 and 28.3 ± 3.6 mm, respectively. All patients were implanted with a Watchman device (diameter, 27.1 ± 2.9 mm). Postoperatively, all patients took anticoagulants orally for 45-60 days, and their mean postoperative follow-up duration was 29.0 ± 12.1 months. Postoperative TEE showed that all had normal positioning of the LAA and ASD/PFO occluders. At 45-60 days after operation, TEE showed that the LAA and ASD/PFO occluder were in the normal position; however, two patients who took warfarin and novel oral anticoagulants, respectively, have developed occluder thrombosis. After adjusted anticoagulant therapy, TEE showed that the thrombus disappeared at 6 months after operation. CONCLUSION: One-stop occlusion is safe and effective for the treatment of adult patients with ASD/PFO and AF. It is also feasible to administer warfarin or novel oral anticoagulants after operation.

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives.

The Pd-catalyzed C-H bond functionalization of lilolidine was investigated. The use of a palladium-diphosphine catalyst associated to acetate bases in DMA was found to promote the regioselective arylation at α-position of the nitrogen atom of lilolidine with a wide variety of aryl bromides. From these α-arylated lilolidines, a second arylation at the ß-position gives the access to α,ß-diarylated lilolidines containing two different aryl groups. The one pot access to α,ß-diarylated lilolidines with two identical aryl groups is also possible by using a larger amount of aryl bromide. The synthesis of 5,6-dihydrodibenzo[a,c]pyrido[3,2,1-jk]carbazoles from lilolidine via three successive direct arylations is also described. Therefore, this methodology provides a straightforward access to several lilolidine derivatives from commercially available compounds via one, two or three C-H bond functionalization steps allowing to tune their biological properties.

Intracoronary electrocardiogram during alcohol septal ablation for hypertrophic obstructive cardiomyopathy predicts myocardial injury size.

Alcohol septal ablation (ASA) has been used widely to treat patients with hypertrophic obstructive cardiomyopathy (HOCM). During the routine ASA procedure, it is difficult to detect the septal injury in real-time. The aim of the present study is to assess myocardial injury during ASA by recording intracoronary electrocardiogram (IC-ECG). From 2012 to 2015, 31 HOCM patients were treated with ASA, and IC-ECG was recorded in 21 patients successfully before and after ethanol injection. The elevation of ST-segment on IC-ECG after ethanol injection was expressed as its ratio to the level before injection or the absolute increasing value. Blood samples were collected before and after ASA for measuring changes in cardiac biomarkers. The ratio value of ST-segment elevation was positively correlated with both the amount of ethanol injected (r = 0.645, P = 0.001) and the myocardial injury size (creatine kinase-MB area under the curve (AUC) of CK-MB) (r = 0.466, P = 0.017). The absolute increment of ST-segment was also positively associated with both the amount of ethanol (r = 0.665, P = 0.001) and AUC of CK-MB (0.685, P = 0.001). However, there was no statistical correlation between the reduction of left ventricular outflow tract gradient and ST-segment elevation. Additionally no severe ASA procedure-related complications were observed in our patients. In conclusion, myocardial injury induced by ethanol injection can be assessed immediately by ST-segment elevation on IC-ECG. This study is the first to show that IC-ECG is a useful method for predicting myocardial injury during ASA in real-time.

Prolyl hydroxylase domain protein 2 silencing enhances the survival and paracrine function of transplanted adipose-derived stem cells in infarcted myocardium.

RATIONALE: Transplantation of stem cells into damaged hearts has had modest success as a treatment for ischemic heart disease. One of the limitations is the poor stem cell survival in the diseased microenvironment. Prolyl hydroxylase domain protein 2 (PHD2) is a cellular oxygen sensor that regulates 2 key transcription factors involved in cell survival and inflammation: hypoxia-inducible factor and nuclear factor-κB. OBJECTIVE: We studied whether and how PHD2 silencing in human adipose-derived stem cells (ADSCs) enhances their cardioprotective effects after transplantation into infarcted hearts. METHODS AND RESULTS: ADSCs were transduced with lentiviral short hairpin RNA against prolyl hydroxylase domain protein 2 (shPHD2) to silence PHD2. ADSCs, with or without shPHD2, were transplanted after myocardial infarction in mice. ADSCs reduced cardiomyocyte apoptosis, fibrosis, and infarct size and improved cardiac function. shPHD2-ADSCs exerted significantly more protection. PHD2 silencing induced greater ADSC survival, which was abolished by short hairpin RNA against hypoxia-inducible factor-1α. Conditioned medium from shPHD2-ADSCs decreased cardiomyocyte apoptosis. Insulin-like growth factor-1 (IGF-1) levels were significantly higher in the conditioned medium of shPHD2-ADSCs versus ADSCs, and depletion of IGF-1 attenuated the cardioprotective effects of shPHD2-ADSC-conditioned medium. Nuclear factor-κB activation was induced by shPHD2 to induce IGF-1 secretion via binding to IGF-1 gene promoter. CONCLUSIONS: PHD2 silencing promotes ADSCs survival in infarcted hearts and enhances their paracrine function to protect cardiomyocytes. The prosurvival effect of shPHD2 on ADSCs is hypoxia-inducible factor-1α dependent, and the enhanced paracrine function of shPHD2-ADSCs is associated with nuclear factor-κB-mediated IGF-1 upregulation. PHD2 silencing in stem cells may be a novel strategy for enhancing the effectiveness of stem cell therapy after myocardial infarction.

A Monolithic CMOS Magnetic Hall Sensor with High Sensitivity and Linearity Characteristics.

This paper presents a fully integrated linear Hall sensor by means of 0.8 µm high voltage complementary metal-oxide semiconductor (CMOS) technology. This monolithic Hall sensor chip features a highly sensitive horizontal switched Hall plate and an efficient signal conditioner using dynamic offset cancellation technique. An improved cross-like Hall plate achieves high magnetic sensitivity and low offset. A new spinning current modulator stabilizes the quiescent output voltage and improves the reliability of the signal conditioner. The tested results show that at the 5 V supply voltage, the maximum Hall output voltage of the monolithic Hall sensor microsystem, is up to ±2.1 V and the linearity of Hall output voltage is higher than 99% in the magnetic flux density range from ±5 mT to ±175 mT. The output equivalent residual offset is 0.48 mT and the static power consumption is 20 mW.

[Application value of three-dimensional female pelvic visualization modeling on transvaginal gynecological ultrasound imaging].

OBJECTIVE: To explore the application value of three-dimensional (3D) female pelvic visualization model on transvaginal gynecological ultrasound imaging. METHODS: The second digital Chinese woman visible human datasets was selected, and a female pelvicvoxel-based model was constructed in Amira software for analog simulation combined with transvaginal gynecological ultrasound. The main structures and the space position variation of female pelvic cavity were observed, and the comparison study with conventional section of ultrasound was carried out. RESULTS: A high accuracy 3D visualization model of female pelvic was successfully constructed, and the anatomy structures can be dynamically and clearly displayed in any section orientation. An analog simulation research was carried out according to the scan mode of gynecological ultrasound, and a series of high resolution images consistent with scan sections of dynamic ultrasound were obtained, which had provided the optimal scan pathway for the fast inspection of the uterus, fallopian tubes and ovaries. CONCLUSION: The 3D female pelvic visualization model based on digital Chinese woman human datasets has provided detailed and accurate anatomy information for transvaginal gynecological ultrasound imaging, which could be the benefit for doctors to understand the ultrasound images of female pelvic, as well as the accurate positioning ability to the lesions of female pelvic cavity.

An Intersubject Brain-Computer Interface Based on Domain-Adversarial Training of Convolutional Neural Network for Online Attention Decoding.

Attention decoding plays a vital role in daily life, where electroencephalography (EEG) has been widely involved. However, training a universally effective model for everyone is impractical due to substantial interindividual variability in EEG signals. To tackle the above challenge, we propose an end-to-end brain-computer interface (BCI) framework, including temporal and spatial one-dimensional (1D) convolutional neural network and domain-adversarial training strategy, namely DA-TSnet. Specifically, DA-TSnet extracts temporal and spatial features of EEG, while it is jointly supervised by task loss and domain loss. During training, DA-TSnet aims to maximize the domain loss while simultaneously minimizing the task loss. We conduct an offline analysis, simulate online experiments on a self-collected dataset of 85 subjects, and real online experiments on 22 subjects. Main results: DA-TSnet achieves a leave-one-subject-out (LOSO) cross-validation (CV) classification accuracy of 89.40% ± 9.96%, outperforming several state-of-the-art attention EEG decoding methods. In simulated online experiments, DA-TSnet achieves an outstanding accuracy of 88.07% ± 11.22%. In real online experiments, it achieves an average accuracy surpassing 86%. Significance: An end-to-end network framework does not rely on elaborate preprocessing and feature extraction steps, which saves time and human workload. Moreover, our framework utilizes domain-adversarial training neural network (DANN) to tackle the challenge posed by the high interindividual variability in EEG signals, which has significant reference value for handling other EEG signal decoding issues. Last, the performance of the DA-TSnet framework in offline and online experiments underscores its potential to facilitate more reliable applications.

Railway track settlement patterns and control measures for multi-tunnel construction underneath a station track group: a case study.

This paper is based on the proximity engineering project of the Baishiyi tunnel group passing under the Chongqing West Station track group. Considering the train load and the spatial relationship of the tunnel and track groups, the settlement patterns, horizontal displacement, and differential settlement of the tunnel-strata-tracks system during the excavation process are studied through theoretical calculations and numerical simulation methods. The results indicate that the tunnel vault, strata, and track settlement deformation patterns are similar. Throughout the tunnel construction process, the tracks underwent uplift, settlement, and eventually stabilized. The settlement trough formed by the excavation of the three tunnels below the track group has an impact range of 25-145 m. Between 35 and 75 m, the differential settlement of the double track gradually increases with excavation. As the tunnel face reaches 75 m, the track differential settlement gradually converges and tends to stabilize. To minimize the impact of underpass tunnel construction on track groups, it is recommended to use a combination of full-section hole grouting and surface reinforcement grouting for ground reinforcement. Additionally, optimizing the construction parameters, including the step length and primary support closure time, and strengthening the locking anchor can further reduce the impact.

Construction and enhancement of government capacity for international communication and promotion of Chinese Wushu.

BACKGROUND: In the process of international communication in Chinese Wushu (ICCW), the government controls the orientation, scale, pace. However, the ICCW currently lacks a standardised government capacity structural system, and a detailed study of framework construction may be required to ensure the smooth development of the ICCW. OBJECTIVES: This study aims to clarify these elements and construct a framework for a governmental capacity system for ICCW. METHODS: For this purpose, an expert interview outline was designed, and in-depth interviews were conducted with 61 experts. Using grounded theory in the qualitative research method, NVivo 12 software was used to conduct a three-level coding analysis of the interview text for data processing and analysis. RESULTS: We extracted 58 opening codes and 11 tree nodes and categorised them into three core categories: supply side government capacity, environment-side government capacity, and demand-side government capacity, accounting for 62.36 %, 24.76 %, and 12.86 % of the total, respectively, which jointly constructed the framework structure system of the governmental capacity system for the ICCW. CONCLUSIONS: This study found that these three-dimensional government capacities have synergistic effects and that multiple measures work together. The government should ensure the supply side's direct promotion effect; the environmental side's indirect influencing effect; and the demand side's internal driving effect to promote ICCW. Meanwhile, a closed-loop systematic study of communication processes should be conducted in combination with communication organisations and individuals.

Corrigendum: Dynamic evolution of left ventricular strain and microvascular perfusion assessed by speckle tracking echocardiography and myocardial contrast echocardiography in diabetic rats: effect of dapagliflozin.

[This corrects the article DOI: 10.3389/fcvm.2023.1109946.].

Construction and in vitro/in vivo targeting of PSMA-targeted nanoscale microbubbles in prostate cancer.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a highly specific biological marker and treatment target for prostate cancer. So ultrasound molecular imaging using PSMA antibody-loaded targeted nanoscale microbubbles (MBs) may contribute to the early diagnosis of prostate cancer. METHODS: PSMA monoclonal antibody-loaded targeted nanoscale MBs were prepared using biotin-avidin technology. Antibody binding was evaluated with immunofluorescence. Using MKN45 gastric cancer cells as controls, the targeting capability of the targeted MBs was observed in prostate cancer cells (LNCaP and C4-2) under optical microscope. Contrast enhancement was monitored by an ultrasound system in C4-2, LNCaP, and MKN45 transplanted tumors in nude mice. The arrival time, time to peak, peak intensity, and duration of contrast enhancement of targeted and blank nanoscale MBs were compared and analyzed. RESULTS: Targeted PSMA monoclonal antibody-loaded nanoscale MBs were successfully synthesized. These MBs were stable and could specifically bind to LNCaP and C4-2 cells in vitro but did not bind to MKN45 cells. There were significant differences in peak intensity and duration of contrast enhancement between targeted and blank nanoscale MBs in both transplanted prostate tumors (P < 0.05). Among the three types of transplanted tumors with targeted nanoscale MBs, the peak intensity was significantly higher in prostate tumors (LNCaP and C4-2) than in gastric tumors (MKN45) (P < 0.05). CONCLUSIONS: PSMA monoclonal antibody-loaded targeted nanoscale MBs can target and bind to prostate cancer cells specifically and allow for obvious contrast enhancement in vivo. Therefore, this study lays a foundation for early diagnosis and targeted therapy for prostate cancer.

Experimental investigation of the penetration of ultrasound nanobubbles in a gastric cancer xenograft.

Nanobubbles as a type of ultrasound contrast agent have attracted much interest in recent years due to their many advantages, such as strong penetrating power and high stability. However, there is still insufficient morphological evidence concerning gas-filled nanobubbles in tumor tissue spaces and tumor angiogenesis. We used a gastric cancer xenograft as an example to study this question. Nanobubbles with a particle size of 435.2 ± 60.53 nm were prepared and compared with SonoVue® microbubbles in vitro and in vivo, and they exhibited a superior contrast imaging effect. After excluding the impact of the nanobubbles in blood vessels through saline flush, we used an ultrasound burst and frozen sectioning to investigate the distribution of nanobubbles in the gastric cancer xenografts and confirmed this by transmission electron microscopy. Preliminary results showed that the nanobubbles were able to pass through the gaps between the endothelial cells in the tumor vascular system to enter the tissue space. These findings could provide morphological evidence for extravascular ultrasound imaging of tumors and serve as a foundation for the application of nanobubbles in extravascular tumor-targeted ultrasonic diagnostics and therapy.