DNA Robots for CRISPR/Cas12a Activity Management and Universal Platforms for Biosensing.

The CRISPR/Cas12a system is a revolutionary genome editing technique that is widely employed in biosensing and molecular diagnostics. However, there are few reports on precisely managing the trans-cleavage activity of Cas12a by simple modification since the traditional methods to manage Cas12a often require difficult and rigorous regulation of core components. Hence, we developed a novel CRISPR/Cas12a regulatory mechanism, named DNA Robots for Enzyme Activity Management (DREAM), by introducing two simple DNA robots, apurinic/apyrimidinic site (AP site) or nick on target activator. First, we revealed the mechanism of how the DREAM strategy precisely regulated Cas12a through different binding affinities. Second, the DREAM strategy was found to improve the selectivity of Cas12a for identifying base mismatch. Third, a modular biosensor for base excision repair enzymes based on the DREAM strategy was developed by utilizing diversified generation ways of DNA robots, and a multi-signal output platform such as fluorescence, colorimetry, and visual lateral flow strip was constructed. Furthermore, we extended logic sensing circuits to overcome the barrier that Cas12a could not detect simultaneously in a single tube. Overall, the DREAM strategy not only provided new prospects for programmable Cas12a biosensing systems but also enabled portable, specific, and humanized detection with great potential for molecular diagnostics.

Self-Assembled DNA Nanospheres Driven by Carbon Dots for MicroRNAs Imaging in Tumor via Logic Circuit.

DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of DNA nanostructures is still lacking. In this work, a facile and mild method is presented for self-assembling polyethylenimine-modified carbon dots (PEI-CDs) and DNA into nanospheres called CANs at room temperature. This makes CANs universally applicable to multiple biological applications involving various types of DNA. Due to the ultra-small size and strong cationic charge of PEI-CDs, CANs exhibit a dense structure with high loading capacity for encapsulated DNA while providing excellent stability by protecting DNA from enzymatic hydrolysis. Additionally, Mg2+ is incorporated into CANs to form Mg@CANs which enriches the performance of CANs and enables subsequent biological imaging applications by providing exogenous Mg2+. Especially, a DNAzyme logic gate system that contains AND and OR Mg@CANs is constructed and successfully delivered to tumor cells in vitro and in vivo. They can be specifically activated by endogenic human apurinic/apyrimidinic endonuclease 1 and recognize the expression levels of miRNA-21 and miRNA-155 at tumor sites by logic biocomputing. A versatile pattern for delivery of diverse DNA and flexible logic circuits for multiple miRNAs imaging are developed.

A metal-organic framework and quantum dot-based ratiometric fluorescent probe for the detection of formaldehyde in food.

A green and sensitive ratio fluorescence strategy was proposed for the detection of formaldehyde (FA) in food based on a kind of metal-organic frameworks (MOFs), MIL-53(Fe)-NO2, and nitrogen-doped Ti3C2 MXene quantum dots (N-Ti3C2 MQDs) with a blue fluorescence at 450 nm. As a type of MOFs with oxidase-like activity, MIL-53(Fe)-NO2 can catalyze o-phenylenediamine (OPD) into yellow fluorescent product 2,3-diaminophenazine (DAP) with a fluorescent emission at 560 nm. DAP has the ability to suppress the blue light of N-Ti3C2 MQDs due to inner filter effect (IFE). Nevertheless, Schiff base reaction can occur between FA and OPD, inhibiting DAP production. This results in a weakening of the IFE which reverses the original fluorescence color and intensity of DAP and N-Ti3C2 MQDs. So, the ratio of fluorescence intensity detected at respective 450 nm and 560 nm was designed as the readout signal to detect FA in food. The linear range of FA detection was 1-200 µM, with a limit of detection of 0.49 µM. The method developed was successfully used to detect FA in food with satisfactory results. It indicates that MIL-53(Fe)-NO2, OPD, and N-Ti3C2 MQDs (MON) system constructed by integrating the mimics enzyme, enzyme substrate, and fluorescent quantum dots has potential application for FA detection in practical samples.

Three-dimensional nasal asymmetry analysis between adolescence and adulthood in postoperative patients with unilateral cleft lip and palate using computed tomography.

AIM: To investigate the differences of the nasal soft and hard tissue asymmetry in postoperative patients with unilateral cleft lip and palate (UCLP) between adolescence and adulthood, and to explore the correlation of nasal soft and hard tissue asymmetry. METHODS: CT data from 47 repaired UCLP patients were included and divided into two groups:1. adolescent group: 23 patients (15 males, 8 females; age: 10-12 years old). 2. adult group: 24 patients (16 males, 8 females; age:18-32 years old). The three-dimensional asymmetry in nasal soft and hard tissues was analyzed. Additionally, the correlation between nasal soft and hard tissue asymmetry was also analyzed. RESULTS: Both the adolescent group and adult group showed asymmetries in nasal soft and hard tissues. Compared to the adolescent group, the adult group had a significantly increased horizontal asymmetry of nasal soft tissues Sbal (P < 0.05). Furthermore, the sagittal asymmetry of soft tissue Glat (P < 0.05), Sbal (P < 0.001), Sni (P < 0.001) and hard tissue LPA (P < 0.05) also increased significantly. In the adult group, there were more landmarks with a correlation between the asymmetry of nasal hard tissue and soft tissue compared to the adolescent group. There were moderate to strong correlations between nasal hard and soft tissue symmetries in the horizontal and sagittal directions (0.444 < r < 764), but no correlation in the vertical direction in the adult group (P > 0.05). CONCLUSIONS: The asymmetry of nasal soft and hard tissues in patients with repaired UCLP becomes more apparent in the horizontal and sagittal dimensions from adolescence to adulthood. The correlation between the asymmetry of nasal hard tissue and soft tissue becomes stronger in the horizontal and sagittal dimensions. These factors should be taken into account when performing treatment for repaired UCLP patients in adolescence and adulthood.

Design, synthesis and biological evaluation of sulfonylamidines as potent c-Met inhibitors by enhancing hydrophobic interaction.

The dysregulation of c-Met kinase has emerged as a significant contributing factor for the occurrence, progression, poor clinical outcomes and drug resistance of various human cancers. In our ongoing pursuit to identify promising c-Met inhibitors as potential antitumor agents, a docking study of the previously reported c-Met inhibitor 7 revealed a large unoccupied hydrophobic pocket, which could present an opportunity for further exploration of structure-activity relationships to improve the binding affinity with the allosteric hydrophobic back pocket of c-Met. Herein we performed structure-activity relationship and molecular modeling studies based on lead compound 7. The collective endeavors culminated in the discovery of compound 21j with superior efficacy to 7 and positive control foretinib by increasing the hydrophobic interaction with the hydrophobic back pocket of c-Met active site.

Design, synthesis, and biological evaluation of thiazole/thiadiazole carboxamide scaffold-based derivatives as potential c-Met kinase inhibitors for cancer treatment.

As part of our continuous efforts to discover novel c-Met inhibitors as antitumor agents, four series of thiazole/thiadiazole carboxamide-derived analogues were designed, synthesised, and evaluated for the in vitro activity against c-Met and four human cancer cell lines. After five cycles of optimisation on structure-activity relationship, compound 51am was found to be the most promising inhibitor in both biochemical and cellular assays. Moreover, 51am exhibited potency against several c-Met mutants. Mechanistically, 51am not only induced cell cycle arrest and apoptosis in MKN-45 cells but also inhibited c-Met phosphorylation in the cell and cell-free systems. It also exhibited a good pharmacokinetic profile in BALB/c mice. Furthermore, the binding mode of 51am with both c-Met and VEGFR-2 provided novel insights for the discovery of selective c-Met inhibitors. Taken together, these results indicate that 51am could be an antitumor candidate meriting further development.

A dual-emission ratiometric fluorescence strategy with enzyme-based inhibition for organophosphorus pesticides determination.

A fast, eco-friendly and accurate ratiometric fluorescent strategy is presented for the determination of organophosphorus pesticides (OPs) using intrinsic dual-emission silica nanoparticles modified with Rhodamine 6G (SiNPs-Rho6G). SiNPs-Rho6G had intrinsic dual-emission at 410 and 550 nm. The substrate acetylcholine was catalyzed by acetylcholinesterase (AChE) to produce thiocholine (TCh). TCh triggered the specific reaction of Ellman's reagent 5, 5-dithiobis (2-nitrobenzoic acid) to obtain 5-thio-2-nitrobenzoic acid, which caused the decrease in fluorescence intensity of SiNPs-Rho6G at 410 nm by the inner filter effect, while the fluorescence intensity of SiNPs-Rho6G at 550 nm was not significantly changed. OPs caused the recovery of the fluorescence at 410 nm by inhibiting the activity of AChE. Thus, the quantitative detection of OPs could be achieved through utilizing the catalytic characteristic of AChE. The linear curve from 0.010 to 0.250 µg mL-1 with a detection limit of 7 ng mL-1 was obtained for the determination of chlorpyrifos (Cpf). The ratiometric probe was used to detect the spiked Cpf in environmental and food samples with good recoveries. Therefore, combined with the dual emission characteristics of SiNPs-Rho6G and the specificity of the enzyme, the ratio fluorescence sensing platform has potential application prospects in OPs determinations.

Nasal asymmetry changes during growth and development in 6- to 12-year-old children with repaired unilateral cleft lip and palate: A 3D computed tomography analysis.

Repaired unilateral cleft lip and palate (UCLP) is often accompanied by the deformity and asymmetry of the nasal region. Three-dimensional analysis was performed to investigate the relationship between nasal soft- and hard-tissue asymmetries, as well as the changes in nasal asymmetry with age, among children with repaired UCLP (age: 6-12 years). Forty-seven patients were included in this study. Their computed tomography records were retrieved for analysis of the 3D asymmetry of 10 landmarks of the nasal soft and hard tissues. We observed that asymmetry was more severe in nasal hard tissues than in soft tissues, particularly in the sagittal dimension. Compared with patients aged 6-9 years old, patients aged 10 to 12 years old had significantly increased vertical asymmetry at the base of the alar groove (Gbase, p = 0.027) and the lateral point of the piriform aperture (LPA), (p < 0.001). The correlation between the LPA and the alar region was weak to moderate (r = 0.290 to 0.488). In conclusion, we found no evidence of growth and development in nasal hard-tissue asymmetry among 6- to 12-year-old children with repaired UCLP, except for the vertical dimension. Nasal soft tissue exhibited a more preferable symmetry than hard tissue, and this could be attributed to the compensatory growth of nasal soft tissue, particularly in the vertical and sagittal dimensions. The weak to moderate correlations between nasal soft-tissue asymmetry and hard-tissue asymmetry were observed in the three dimensions. Surgeons should consider these factors when repositioning the nasal alar and controlling the size of the nostrils.

Development and validation of a prediction model for tuberculous pleural effusion: a large cohort study and external validation.

BACKGROUND: Distinguishing tuberculous pleural effusion (TPE) from non-tuberculosis (TB) benign pleural effusion (BPE) remains to be a challenge in clinical practice. The aim of the present study was to develop and validate a novel nomogram for diagnosing TPE. METHODS: In this retrospective analysis, a total of 909 consecutive patients with TPE and non-TB BPE from Ningbo First Hospital were divided into the training set and the internal validation set at a ratio of 7:3, respectively. The clinical and laboratory features were collected and analyzed by logistic regression analysis. A diagnostic model incorporating selected variables was developed and was externally validated in a cohort of 110 patients from another hospital. RESULTS: Six variables including age, effusion lymphocyte, effusion adenosine deaminase (ADA), effusion lactatedehy drogenase (LDH), effusion LDH/effusion ADA, and serum white blood cell (WBC) were identified as valuable parameters used for developing a nomogram. The nomogram showed a good diagnostic performance in the training set. A novel scoring system was then established based on the nomogram to distinguish TPE from non-TB BPE. The scoring system showed good diagnostic performance in the training set [area under the curve (AUC) (95% confidence interval (CI)), 0.937 (0.917-0.957); sensitivity, 89.0%, and specificity, 89.5%], the internal validation set [AUC (95%CI), 0.934 (0.902-0.966); sensitivity, 88.7%, and specificity, 90.3%], and the external validation set [(AUC (95%CI), 0.941 (0.891-0.991); sensitivity, 93.6%, and specificity, 87.5%)], respectively. CONCLUSIONS: The study developed and validated a novel scoring system based on a nomogram originated from six clinical parameters. The novel scoring system showed a good diagnostic performance in distinguishing TPE from non-TB BPE and can be conveniently used in clinical settings.

Orbital apex syndrome secondary to apical periodontitis of a tooth: a case report.

BACKGROUND: Orbital apex syndrome (OAS) is a rare disease with a noticeable mortality rate. Although its etiology has been repeatedly assessed, few reports have concentrated on odontogenic infection. We presented a rare case of OAS secondary to apical periodontitis. CASE PRESENTATION: A 61-year-old male was admitted to our hospital for a 3-day history of left orbital and head pain, along with diplopia for 1-day. He also had toothache symptoms before his admission. Due to the atypical early symptoms of orbital apex and cranial nerve injury, no timely and effective diagnosis and treatment were initially provided. However, as the disease progressed and complications occurred, we timely adjusted the diagnosis and successfully controlled the infection. During the one-year follow-up, no recurrence of inflammation was observed; nevertheless, the ptosis and ophthalmoplegia persisted. CONCLUSIONS: OAS is a rare, while severe complication of odontogenic infection. This case had various symptoms and nerve injury in the orbital apical area. When disease is atypical in its early stages, treatment is easily overlooked. Early detection and suspicion of orbital apex-related complications should be heightened.

Safety and efficacy of low-dose rt-PA with tirofiban to treat acute non-cardiogenic stroke: a single-center randomized controlled study.

BACKGROUND AND PURPOSE: The recanalization rate after intravenous thrombolysis (IVT) is not enough and there is still the possibility of re-occlusion. We aim to investigate the effectiveness and safety of infusing tirofiban after IVT. METHODS: We performed a prospective controlled study of 60 patients with acute non-cardiogenic ischemic stroke who were hospitalized in Yantai Yuhuangding Hospital from January 2018 to December 2019. The patients were divided into 2 groups: those who received tirofiban for 24 h after IVT (rt-PA + T group) and those who did not receive postprocedural intravenous tirofiban (rt-PA group). The rt-PA + T group received low-dose rt-PA (0.6 mg/kg). The rt-PA group received standard dose rt-PA (0.9 mg/kg). The main outcome measure were safety, included the symptomatic intracranial hemorrhage (sICH), any ICH, severe systemic bleeding, and mortality. The secondary outcome measure is curative efficacy which were evaluated by the 7d-NIHSS score and functional outcomes at 90 days. During hospitalization, the deterioration of neurological function was recorded. RESULTS: All patients completed the follow-up with complete data, there were 30 patients in each of groups. The general characteristics between the two group patients had no statistically significant differences. Compared with the rt-PA + T group and the rt-PA group, in terms of safety, the rates of the sICH, severe systemic bleeding, and mortality in both groups were 0, and there was no statistically significant difference in the rates of any ICH between the two groups (10.0% vs. 3.3%, P = 0.306). In terms of efficacy, the rate of the early neurological deterioration events (END) was no statistical significance (0 vs. 6.6%, P = 0.246). There was no significant difference in the NIHSS score between the two groups before the IVT, and also at 24 h, however, the 7d-NIHSS score was lower in the rt-PA + T group compared with the rt-PA group (2.33 ± 1.85 vs. 4.80 ± 4.02, P = 0.004). At 90 days, 83.3% of patients in the rt-PA + T group had favorable functional outcomes compared with 60.0% of patients in the rt-PA group (P = 0.045). CONCLUSIONS: Low-dose rt-PA combined with tirofiban in acute non-cardiogenic ischemic stroke did not increase the risk of ICH, and mortality, and it was associated with neurological improvement. TRIAL REGISTRATION: The trial has been registered at the ChiCTR and identified as ChiCTR1800014666 (28/01/2018).

Clinical and Preclinical Neuroimaging Changes in Spinocerebellar Ataxia Type 12: A Study of Three Chinese Pedigrees.

BACKGROUND: Spinocerebellar ataxia type 12 (SCA12) is a rare SCA subtype with unclear clinical and imaging features. Also, the radiological changes in prodromal and early stages remain unknown. METHODS: Ten symptomatic and two pre-symptomatic cases from three Chinese pedigrees received clinical assessments and imaging studies including routine magnetic resonance imaging (MRI), diffusion kurtosis imaging (DKI), and positron emission tomography (PET) using 18F-flurodeoxyglucose (FDG) to investigate glucose metabolism in brain and 18F-vesicle monoamine transporter 2 (VMAT2) to inspect the integrity of the dopaminergic neuron. Seventy-two healthy individuals were recruited as controls in the quantitative FDG-PET analysis. Imaging parameters were compared between symptomatic and presymptomatic cases with different disease durations. RESULTS: Patients displayed prominent action tremor, moderate ataxia, and subtle parkinsonism with poor levodopa-response. MRI showed extensive but heterogeneous cerebral atrophy, which was most evident in the frontoparietal lobes. Cerebellar atrophy was apparent in later stages. DKI detected impaired fibers in the cerebellar peduncles. In both symptomatic and pre-symptomatic cases, PET-CT showed an earlier FDG decline than atrophic changes in multiple regions, and the frontoparietal lobes were the earliest and most severe. However, the VMAT2 density were normal in the putamen and caudate nucleus of most cases (7/8). CONCLUSIONS: We first found that hypometabolism in the cerebral cortex, but not cerebellum, is an early and prominent change in SCA12. The integrity of presynaptic dopaminergic neurons remains largely spared during the whole disease process.

Cisplatin synergizes with PRLX93936 to induce ferroptosis in non-small cell lung cancer cells.

Ferroptosis is a newly identified type of regulated cell death that is affected by lipid peroxidation and reactive oxygen species (ROS). In the current study, we showed that cisplatin and PRLX93936, an analog of erastin that has been tested in clinical trials, demonstrated synergistic effects against non-small cell lung cancer (NSCLC) cells. Cotreatment with cisplatin and PRLX93936 induced ferroptosis, as evidenced by the upregulation of ROS, lipid peroxidation and Fe2+. Further investigation revealed that cotreatment with cisplatin and PRLX93936 inhibited GPX4 and that overexpression of GPX4 prevented cell death. Moreover, the Nrf2/Keap1 pathway also regulated the sensitivity to cisplatin and PRLX93936 in NSCLC cells. Nrf2 silencing increased this sensitivity while inhibition of Keap1 attenuated it. Overall, our data reveal a new effective treatment for NSCLC by synergizing cisplatin and PRLX93936 to induce ferroptosis.

Histologic subtype classification of non-small cell lung cancer using PET/CT images.

PURPOSES: To evaluate the capability of PET/CT images for differentiating the histologic subtypes of non-small cell lung cancer (NSCLC) and to identify the optimal model from radiomics-based machine learning/deep learning algorithms. METHODS: In this study, 867 patients with adenocarcinoma (ADC) and 552 patients with squamous cell carcinoma (SCC) were retrospectively analysed. A stratified random sample of 283 patients (20%) was used as the testing set (173 ADC and 110 SCC); the remaining data were used as the training set. A total of 688 features were extracted from each outlined tumour region. Ten feature selection techniques, ten machine learning (ML) models and the VGG16 deep learning (DL) algorithm were evaluated to construct an optimal classification model for the differential diagnosis of ADC and SCC. Tenfold cross-validation and grid search technique were employed to evaluate and optimize the model hyperparameters on the training dataset. The area under the receiver operating characteristic curve (AUROC), accuracy, precision, sensitivity and specificity was used to evaluate the performance of the models on the test dataset. RESULTS: Fifty top-ranked subset features were selected by each feature selection technique for classification. The linear discriminant analysis (LDA) (AUROC, 0.863; accuracy, 0.794) and support vector machine (SVM) (AUROC, 0.863; accuracy, 0.792) classifiers, both of which coupled with the ℓ2,1NR feature selection method, achieved optimal performance. The random forest (RF) classifier (AUROC, 0.824; accuracy, 0.775) and ℓ2,1NR feature selection method (AUROC, 0.815; accuracy, 0.764) showed excellent average performance among the classifiers and feature selection methods employed in our study, respectively. Furthermore, the VGG16 DL algorithm (AUROC, 0.903; accuracy, 0.841) outperformed all conventional machine learning methods in combination with radiomics. CONCLUSION: Employing radiomic machine learning/deep learning algorithms could help radiologists to differentiate the histologic subtypes of NSCLC via PET/CT images.

Indirect comparison of the diagnostic performance of 18F-FDG PET/CT and MRI in differentiating benign and malignant ovarian or adnexal tumors: a systematic review and meta-analysis.

OBJECTIVE: To compare the value of fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) and magnetic resonance imaging (MRI) in differentiating benign and malignant ovarian or adnexal tumors. MATERIALS AND METHODS: English articles reporting on the diagnostic performance of MRI or 18F-FDG PET/CT in identifying benign and malignant ovarian or adnexal tumors published in PubMed and Embase between January 2000 and January 2021 were included in the meta-analysis. Two authors independently extracted the data. If the data presented in the study report could be used to construct a 2 × 2 contingency table comparing 18F-FDG PET/CT and MRI, the studies were selected for the analysis. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of the included studies. Forest plots were generated according to the sensitivity and specificity of 18F-FDG PET/CT and MRI. RESULTS: A total of 27 articles, including 1118F-FDG PET/CT studies and 17 MRI studies on the differentiation of benign and malignant ovarian or adnexal tumors, were included in this meta-analysis. The pooled sensitivity and specificity for 18F-FDG PET/CT in differentiating benign and malignant ovarian or adnexal tumors were 0.94 (95% CI, 0.87-0.97) and 0.86 (95% CI, 0.79-0.91), respectively, and the pooled sensitivity and specificity for MRI were 0.92 (95% CI: 0.89-0.95) and 0.85 (95% CI: 0.79-0.89), respectively. CONCLUSION: While MRI and 18F-FDG PET/CT both showed to have high and similar diagnostic performance in the differential diagnosis of benign and malignant ovarian or adnexal tumors, MRI, a promising non-radiation imaging technology, may be a more suitable choice for patients with ovarian or accessory tumors. Nonetheless, prospective studies directly comparing MRI and 18F-FDG PET/CT diagnostic performance in the differentiation of benign and malignant ovarian or adnexal tumors are needed.

Resection of Giant Tumor of Chest Wall under Cardiopulmonary Bypass after Neoadjuvant Chemoradiotherapy: A Case Report.

Osteosarcoma, one of the most common sources of bone malignant tumors, often occurs at the epiphysis, such as in the distal femoral and proximal tibia, but seldom occurs at the costa. Here, we present the case of a 15-year-old girl with giant osteosarcoma on the chest wall. Osteosarcoma is extremely malignant and has a high death rate. We surgically resected the osteosarcoma using cardiopulmonary bypass and administered neoadjuvant chemoradiotherapy.

MR extracellular volume mapping and non-contrast T1ρ mapping allow early detection of myocardial fibrosis in diabetic monkeys.

OBJECTIVE: To detect diffuse myocardial fibrosis in different severity levels of left ventricular diastolic dysfunction (DD) in spontaneous type 2 diabetes mellitus (T2DM) rhesus monkeys. METHODS: Eighteen spontaneous T2DM and nine healthy monkeys were studied. Echocardiography was performed for diastolic function classification. Cardiac magnetic resonance (CMR) imaging was performed to obtain extracellular volume fraction (ECV) maps and T1ρ maps at two different spin-locking frequencies. ECV values, T1ρ values, and myocardial fibrosis index (mFI) values which are based on the dispersion of T1ρ, were calculated. Global peak diastolic longitudinal strain rates (GSrL) were also obtained. RESULTS: Echocardiography results showed mild DD in nine T2DM monkeys and moderate DD in the other nine. The global ECV values were significantly different among healthy animals as compared with animals with mild DD or moderate DD, and the ECV values of animals with moderate DD were significantly higher as compared with those of mild DD. The mFI values increased progressively from healthy animals to those with mild DD and then to those with moderate DD. Diastolic function indicators (e.g., early diastolic mitral annulus velocity, GSrL) correlated well with ECV and mFI. CONCLUSIONS: Monkeys with T2DM exhibit increased ECV, T1ρ, and mFI values, which may be indicative of the expansion of extracellular volume and the deposition of excessive collagen. T1ρ mapping may have the potential to be used for diffuse myocardial fibrosis assessment. KEY POINTS: • Monkeys with T2DM exhibit increased ECV, T1ρ, and mFI values, which may be indicative of the expansion of extracellular volume and the deposition of excessive collagen. • The relationship between diastolic dysfunction and diffuse myocardial fibrosis may be demonstrated by imaging markers. • Non-contrast T1ρ mapping may have the potential to be used for diffuse myocardial assessment.

miR-21 promotes proliferation and inhibits apoptosis of hepatic stellate cells through targeting PTEN/PI3K/AKT pathway.

To investigate the effect of microRNA 21 (miR-21) on hepatic stellate cells (HSCs) proliferation and apoptosis, and further to study its potential mechanisms. LX-2 cells were divided into miR-21 mimic group (Mimic), miR-21 mimic negative control group (NM), miR-21 inhibitor group (Inhibitor), miR-21 inhibitor negative control group (NC), and blank control group (Control). The cell proliferation was detected by CCK-8 assay and the cell migration and invasion were detected by scratch and transwell assay. Cell cycle and apoptosis were detected by flow cytometry. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß1 were detected by enzyme-linked immunosorbent assay (ELISA). Proliferation, apoptosis, and phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway related genes and proteins were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. The cells proliferation, migration, and invasion were promoted in Mimic group. The levels of IL-6, TNF-α, and TGF-ß1 were increased after miR-21 administration. The expression of α-smooth muscle actin (SMA) and collagen 1 (Colla1) were increased, while Bax/B-cell lymphoma (Bcl)-2 ratio and programed cell death 4 (PDCD4) were reduced after miR­21 treatment. Meanwhile, the mRNA and protein expression of PTEN were reduced and PI3K/AKT pathway been promoted. Our study demonstrated that miR-21 could promote proliferation and inhibit apoptosis of HSCs, and its mechanism may be related to PTEN/PI3K/AKT pathway.

2D/3D CMR tissue tracking versus CMR tagging in the assessment of spontaneous T2DM rhesus monkeys with isolated diastolic dysfunction.

BACKGROUND: Spontaneous T2DM in rhesus monkeys manifests as isolated diastolic dysfunction in the early stage of diabetic cardiomyopathy, similar to humans. Myocardial deformation measurements have emerged as a superior way to measure left ventricular (LV) function in the early stage of cardiac dysfunction, making it possible to further evaluate early-stage LV dysfunction in spontaneous T2DM rhesus monkeys. METHODS: Spontaneous T2DM rhesus monkeys with isolated diastolic dysfunction (T2DM-DD, n = 10) and corresponding nondiabetic healthy animals (ND, n = 9) were prospectively scanned for a CMR study. Circumferential and longitudinal peak systolic strain (Ecc, Ell), time to peak strain (tEcc, tEll) and peak diastolic strain rate (CSR, LSR) obtained from 2D/3D CMR-TT were compared with those obtained from CMR tagging separately. In addition, all CMR imaging protocols were performed twice in 9 ND animals to assess test-retest reproducibility. RESULTS: Compared with the ND group, the T2DM-DD monkeys demonstrated significantly impaired LV Ecc (- 10.63 ± 3.23 vs - 14.18 ± 3.19, p < 0.05), CSR (65.50 ± 14.48 vs 65.50 ± 14.48, p < 0.01), Ell (- 9.11 ± 2.59 vs - 14.17 ± 1.68, p < 0.05), and LSR (59.43 ± 19.17 vs 108.46 ± 22.33, p < 0.01) with the tagging. Only Ecc (- 13.10 ± 2.47 vs - 19.03 ± 3.69, p < 0.01) and CSR (148.90 ± 31.27 vs 202.00 ± 51.88, p < 0.01) were significantly reduced with 2D CMR-TT, and only Ecc (- 13.77 ± 1.98 vs - 17.26 ± 3.78, p < 0.05) was significantly reduced with 3D CMR-TT. Moreover, 2D/3D CMR-TT-derived Ecc and CSR correlated with the corresponding tagging values collectively, with a statistically significant ICC value (p < 0.05). Test-retest repeatability analysis showed that most tagging-derived biomarkers had acceptable repeatability (p < 0.01). In addition, 2D CMR-TT-derived indicators were poorer than those derived from the tagging method but better than those obtained using the 3D method, with larger ICCs except for tEcc (p < 0.05). CONCLUSIONS: LV systolic and diastolic deformations were impaired in spontaneous T2DM rhesus monkeys previously diagnosed with isolated diastolic dysfunction by echocardiography. The 2D CMR-TT-derived Ecc and CSR were effective in the evaluation of the myocardial systolic and diastolic functions of early-diabetic cardiomyopathy, with relatively higher test-retest reproducibility and acceptable correlation with the tagging method compared with the 3D CMR-TT method.

Contourlet-based hippocampal magnetic resonance imaging texture features for multivariant classification and prediction of Alzheimer's disease.

The study is aimed to assess whether the addition of contourlet-based hippocampal magnetic resonance imaging (MRI) texture features to multivariant models improves the classification of Alzheimer's disease (AD) and the prediction of mild cognitive impairment (MCI) conversion, and to evaluate whether Gaussian process (GP) and partial least squares (PLS) are feasible in developing multivariant models in this context. Clinical and MRI data of 58 patients with probable AD, 147 with MCI, and 94 normal controls (NCs) were collected. Baseline contourlet-based hippocampal MRI texture features, medical histories, symptoms, neuropsychological tests, volume-based morphometric (VBM) parameters based on MRI, and regional CMgl measurement based on fluorine-18 fluorodeoxyglucose-positron emission tomography were included to develop GP and PLS models to classify different groups of subjects. GPR1 model, which incorporated MRI texture features and was based on GPG, performed better in classifying different groups of subjects than GPR2 model, which used the same algorithm and had the same data as GPR1 except that MRI texture features were excluded. PLS model, which included the same variables as GPR1 but was based on the PLS algorithm, performed best among the three models. GPR1 accurately predicted 82.2% (51/62) of MCI convertors confirmed during the 2-year follow-up period, while this figure was 53 (85.5%) for PLS model. GPR1 and PLS models accurately predicted 58 (79.5%) vs. 61 (83.6%) of 73 patients with stable MCI, respectively. For seven patients with MCI who converted to NCs, PLS model accurately predicted all cases (100%), while GPR1 predicted six (85.7%) cases. The addition of contourlet-based MRI texture features to multivariant models can effectively improve the classification of AD and the prediction of MCI conversion to AD. Both GPR and LPS models performed well in the classification and predictive process, with the latter having significantly higher classification and predictive accuracies. Advances in knowledge: We combined contourlet-based hippocampal MRI texture features, medical histories, symptoms, neuropsychological tests, volume-based morphometric (VBM) parameters, and regional CMgl measurement to develop models using GP and PLS algorithms to classify AD patients.