A nomogram model for predicting intramyocardial hemorrhage post-PCI based on SYNTAX score and clinical features.

OBJECTIVE: The aim of this study is to develop a nomogram model for predicting the occurrence of intramyocardial hemorrhage (IMH) in patients with Acute Myocardial Infarction (AMI) following Percutaneous Coronary Intervention (PCI). The model is constructed utilizing clinical data and the SYNTAX Score (SS), and its predictive value is thoroughly evaluated. METHODS: A retrospective study was conducted, including 216 patients with AMI who underwent Cardiac Magnetic Resonance (CMR) within a week post-PCI. Clinical data were collected for all patients, and their SS were calculated based on coronary angiography results. Based on the presence or absence of IMH as indicated by CMR, patients were categorized into two groups: the IMH group (109 patients) and the non-IMH group (107 patients). The patients were randomly divided in a 7:3 ratio into a training set (151 patients) and a validation set (65 patients). A nomogram model was constructed using univariate and multivariate logistic regression analyses. The predictive capability of the model was assessed using Receiver Operating Characteristic (ROC) curve analysis, comparing the predictive value based on the area under the ROC curve (AUC). RESULTS: In the training set, IMH post-PCI was observed in 78 AMI patients on CMR, while 73 did not show IMH. Variables with a significance level of P < 0.05 were screened using univariate logistic regression analysis. Twelve indicators were selected for multivariate logistic regression analysis: heart rate, diastolic blood pressure, ST segment elevation on electrocardiogram, culprit vessel, symptom onset to reperfusion time, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, high-sensitivity troponin T (HS-TnT), and SYNTAX Score. Based on multivariate logistic regression results, two independent predictive factors were identified: HS-TnT (Odds Ratio [OR] = 1.61, 95% Confidence Interval [CI]: 1.21-2.25, P = 0.003) and SS (OR = 2.54, 95% CI: 1.42-4.90, P = 0.003). Consequently, a nomogram model was constructed based on these findings. The AUC of the nomogram model in the training set was 0.893 (95% CI: 0.840-0.946), and in the validation set, it was 0.910 (95% CI: 0.823-0.970). Good consistency and accuracy of the model were demonstrated by calibration and decision curve analysis. CONCLUSION: The nomogram model, constructed utilizing HS-TnT and SS, demonstrates accurate predictive capability for the risk of IMH post-PCI in patients with AMI. This model offers significant guidance and theoretical support for the clinical diagnosis and treatment of these patients.

Reduced cerebral cortex thickness is related to overexpression of exosomal miR-146a-5p in medication-free patients with major depressive disorder.

BACKGROUND: Previous studies have confirmed that miR-146a-5p overexpression suppresses neurogenesis, thereby enhancing depression-like behaviors. However, it remains unclear how miR-146a-5p dysregulation produces in vivo brain structural abnormalities in patients with major depressive disorder (MDD). METHODS: In this case-control study, we combined cortical morphology analysis of magnetic resonance imaging (MRI) and miR-146a-5p quantification to investigate the neuropathological effect of miR-146a-5p on cortical thickness in MDD patients. Serum-derived exosomes that were considered to readily cross the blood-brain barrier and contain miR-146a-5p were isolated for miRNA quantification. Moreover, follow-up MRI scans were performed in the MDD patients after 6 weeks of antidepressant treatment to further validate the clinical relevance of the relationship between miR-146a-5p and brain structural abnormalities. RESULTS: In total, 113 medication-free MDD patients and 107 matched healthy controls were included. Vertex-vise general linear model revealed miR-146a-5p-dependent cortical thinning in MDD patients compared with healthy individuals, i.e., overexpression of miR-146a-5p was associated with reduced cortical thickness in the left orbitofrontal cortex (OFC), anterior cingulate cortex, bilateral lateral occipital cortices (LOCs), etc. Moreover, this relationship between baseline miR-146a-5p and cortical thinning was nonsignificant for all regions in the patients who had received antidepressant treatment, and higher baseline miR-146a-5p expression was found to be related to greater longitudinal cortical thickening in the left OFC and right LOC. CONCLUSIONS: The findings of this study reveal a relationship between miR-146a-5p overexpression and cortical atrophy and thus may help specify the in vivo mediating effect of miR-146a-5p dysregulation on brain structural abnormalities in patients with MDD.

Vital pulp therapy following pulpotomy in immature permanent teeth with carious exposure.

This prospective cohort study aimed to evaluate the clinical outcomes of vital pulp therapy (VPT) with the use of iRoot BP Plus (Innovative Bioceramics, Vancouver, Canada) for immature permanent teeth of patients aged from 6 to 10 years with pulp exposure resulting from dental caries and determine the impact of preoperative factors on VPT. Forty-six immature permanent teeth with dental caries underwent pulpotomy using iRoot BP Plus following a standardized protocol. Postoperative follow-ups were conducted on the first 3, 6 and 12 months post-surgery, then annually afterward. Successful treatment outcomes were defined based on clinical and radiographic evaluations. Statistical analysis was performed using the Fisher exact test, with p < 0.05 considered for statistical significance. Forty-four patients included in this study were 8.48 ± 1.49 years old and were followed up for 6 to 36 months. The overall success rate of pulpotomy was found to be 90.9% (40/44). None of the physical examination findings and symptoms significantly affected VPT prognosis (p > 0.05). Immature permanent teeth with caries-induced pulp exposed in patients aged 6 to 10 years can be effectively treated with pulpotomy using iRoot sBP Plus.

ORS-Pred: An optimized reduced scheme-based identifier for antioxidant proteins.

Antioxidant proteins can terminate a chain of reactions caused by free radicals and protect cells from damage. To identify antioxidant proteins rapidly, a computational model was proposed based on the optimized recoding scheme, sequence information and machine learning methods. First, over 600 recoding schemes were collected to build a scheme set. Then, the original sequence was recoded as a reduced expression whose g-gap dipeptides (g = 0, 1, 2) were used as the features of proteins. Furthermore, a random forest method was used to evaluate the classification ability of the obtained dipeptide features. After going through all schemes, the best predictive performance scheme was chosen as the optimized reduction scheme. Finally, for the RF method, a grid search strategy was used to select a better parameter combination to identify antioxidant proteins. In the experiment, the present method correctly recognized 90.13-99.87% of the antioxidant samples. Other experimental results also proved that the present method was efficient to identify antioxidant proteins. Finally, we also developed a web server that was freely accessible to researchers.

Prediction of N7-methylguanosine sites in human RNA based on optimal sequence features.

N-7 methylguanosine (m7G) modification is a ubiquitous post-transcriptional RNA modification which is vital for maintaining RNA function and protein translation. Developing computational tools will help us to easily predict the m7G sites in RNA sequence. In this work, we designed a sequence-based method to identify the modification site in human RNA sequences. At first, several kinds of sequence features were extracted to code m7G and non-m7G samples. Subsequently, we used mRMR, F-score, and Relief to obtain the optimal subset of features which could produce the maximum prediction accuracy. In 10-fold cross-validation, results showed that the highest accuracy is 94.67% achieved by support vector machine (SVM) for identifying m7G sites in human genome. In addition, we examined the performances of other algorithms and found that the SVM-based model outperformed others. The results indicated that the predictor could be a useful tool for studying m7G. A prediction model is available at https://github.com/MapFM/m7g_model.git.

MicroRNA-146a negatively regulates IL-33 in activated group 2 innate lymphoid cells by inhibiting IRAK1 and TRAF6.

Type II innate lymphoid cells (ILC2) play a very important role in the pathogenesis of allergic asthma. This study aims to investigate whether miR-146a inhibition of asthma is related with interleukin (IL)-33 signaling path way in ILC2 and the underlying mechanisms. Asthma mice model was induced by ovalbumin. miRNA146a mimics was administrated to asthma mice or transfected to activated ILC2 purified from asthma mice lung. RT-PCR was used to detect miRNA146a level in lung tissue and ILC2. IL-5 and IL-13 levels in culture supernatant were detected by flow cytometry. Interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), signal transducer and activator of transcription 1 (STAT1) protein expression levels were detected by western blot. miR-146a directly inhibited ILC2 function and suppressed ILC2 proliferation both in vivo and in vitro. During stimulation of ILC2, miR-146a expression gradually increased with a decrease of cell proliferation. Modulation of ILC2 function by miR-146a may depend on IL-33/interleukin 1 receptor-like 1 (IL1RL1 or ST2) signaling through inhibiting IRAK1 and TRAF6.miR-146a can inhibit IRAK1 and TRAF6, downstream molecules of ST2 signal pathway, thereby negatively regulate IL-33/ST2-activated ILC2 to inhibit asthma. Targeting miR-146 maybe a novel strategy for the treatment of allergic asthma.

Combination of TLR agonist and miR146a mimics attenuates ovalbumin-induced asthma.

BACKGROUND: microRNA-146a has been reported to be a regulator in the process of attenuating asthma by inhibiting Toll-like receptor 2 (TLR2) pathway. This study aimed to investigate how miR146a-inhibitor affect the symptom of asthma and the underlying mechanisms. METHODS: Ovalbumin (OVA)-induced allergic asthma mice model was established by intraperitoneal injection with 20 µg of OVA. Total cells and differential inflammatory cells in bronchoalveolar lavage fluid were counted by flow cytometry. The expression levels of molecules and cytokines in TLR2 signaling pathway were detected by Q-PCR and ELISA. RESULTS: miR146a-inhibitor attenuated OVA-induced allergic asthma by increasing Th1 cytokines in OVA-induced allergic asthma model, and the treatment of miR146a-inhibitor can reduce the inflammation caused by asthma, followed by the down-regulation of IL-5 and IL-13 in sorted ILC2. The inhibition of miR-146a significantly reduced symptoms of asthma model with TLR2-related molecules being up-regulated. CONCLUSION: It was found that miR-146a is an important regulator in OVA-induced allergic asthma model, which can relieve symptoms of asthma through regulating TLR2 pathway. These findings provide a theoretical basis for solving asthma in clinical treatment.

Simultaneous removal of rhodamine B and Cr(VI) from water using cellulose carbon nanofiber incorporated with bismuth oxybromide: The effect of cellulose pyrolysis temperature on photocatalytic performance.

A series of biomass cellulose-derived carbon nanofibers (CCNF) were prepared at different pyrolysis temperatures in this study. Subsequently, this CCNF was combined with bismuth oxybromide (BiOBr) to form BiOBr/CCNF composite. The feasibility of BiOBr/CCNF as photocatalyst was investigated for the treatment against organic dye, rhodamine B (RhB) and inorganic metal ion, hexavalent chromium (Cr(VI)). The effect of the pyrolysis temperature on the properties (e.g., crystalline structure, functional group distribution, and graphitization degree) of the prepared CCNF was investigated in relation to its photocatalytic performance. A pyrolysis temperature over 800 °C resulted in CCNF with higher degrees of graphitization which was accompanied by a better photocatalytic performance of its composite against RhB and Cr(VI). Their reaction kinetic rates were estimated as 8.15 × 10-2 and 0.21 mmol/g/h, respectively (at the initial concentration of 10 mg/L), while their quantum yield values were 1.56 × 10-6 and 3.83 × 10-6 molecules per photon, respectively. BiOBr/CCNF catalysts were efficient enough to simultaneously remove RhB and Cr(VI) through the generation of active oxidative and reductive oxygen species, respectively. The strategies used in this study offer a new pathway for preparing cost-effective photocatalysts with biomass derived carbonaceous materials for the efficient removal of multicomponent contaminants in water.

Exploring and comparing two means of preparing and fractionating oligomeric proanthocyanidins from mangosteen pericarp: gel filtration chromatography and progressive solvent precipitation.

The preparation and fractionation of oligomeric proanthocyanidins (OPCs) are particularly important for the application of tannins in the biomedical field. By use of two different methods-gel filtration chromatography (GFC) with Sephadex LH-20 and progressive solvent precipitation-the OPCs were prepared and fractionated from mangosteen pericarp. The fractions were compared by reversed-phase and normal-phase high-performance liquid chromatography-electrospray ionization mass spectrometry and gel permeation chromatography. GFC directly purified oligomers (monomer to pentamer) with polydispersity values close to 1 and generated fractions with a higher level of total phenols (800.59 mg gallic acid equivalents per gram) but a lower yield (7.72%). Progressive solvent precipitation rapidly prepared and fractionated OPCs with a lower level of total phenols (609.57 mg gallic acid equivalents per gram) but a higher yield (24.74%) and higher polydispersity. Additionally, we found pronounced structural and quantitative differences among different tannin-rich fractions, and fractions obtained by GFC better reflected the structural diversity and complexity of OPCs from mangosteen pericarp. This study presents different ways of preparing and fractionating OPCs in the biomedical field.

miR-146a Mimics Attenuate Allergic Airway Inflammation by Impacted Group 2 Innate Lymphoid Cells in an Ovalbumin-Induced Asthma Mouse Model.

BACKGROUND: The prevalence of allergic asthma has increased dramatically. Previous studies have found that the microRNA 146a (miR-146a) expression in asthma inhibits cell proliferation and promotes apoptosis of bronchial smooth muscle cells. We aimed to investigate the effect of miR-146a mimics on ovalbumin (OVA)-induced asthma in a mouse model. METHODS: Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) was measured by flow cytometry. Levels of OVA-specific immunoglobulin E (IgE) in serum and cytokines in BALF were examined by enzyme-linked immunosorbent assay. For monitoring the airway, the Penh value (% baseline) was measured using a whole-body plethysmograph. RESULTS: In OVA-induced asthmatic mice, miR-146a significantly suppressed the infiltration of inflammatory cells in BALF and decreased the levels of OVA-specific IgE and T helper 2 cell type cytokines. In addition, miR-146a inhibited the OVA-induced airway hyperresponsiveness and the group 2 innate lymphoid cell responses. Moreover, the effects of miR-146a mimics were dependent on interleukin 33 stimulation. CONCLUSIONS: Our results suggest that miR-146a mimics might serve as an attractive candidate for further preclinical studies as an anti-inflammatory treatment of asthma.

Curcumin ameliorates severe influenza pneumonia via attenuating lung injury and regulating macrophage cytokines production.

Curcumin, an active phenolic agent extract from the Curcuma longa, exhibits excellent anti-cancer, anti-inflammation, and neuroprotective effects. We aimed to investigate the anti-influenza role of curcumin in vitro and in vivo. The effect of curcumin on replication of influenza A virus (IAV) was examined in human lung cancer cell line A549, as well as in a mouse model. Curcumin could inhibit IAV in vitro and alleviate the severity of the disease in the mouse after infection with IAV. The results also indicated that curcumin could trigger expression of Heme oxygenase-1 in vivo and attenuate IAV-induced injury to the lung tissue. Furthermore, curcumin could regulate immune response following IAV infection through inhibiting production of local inflammatory cytokines. In addition, curcumin was found to inhibit NF-κB signalling in macrophages, as well as the subsequent production of cytokines/chemokines responding to IAV infection, by enhancing IκBα and AMPK. Our current study supports the potential of curcumin as a promising treatment against IAV infection, whose effect may be mediated by regulating immune response to prevent injury to the lung tissue.

Characteristics and prognostic value of cardiac magnetic resonance strain analysis in patients with different phenotypes of heart failure.

Background: Strain analysis of cardiac magnetic resonance imaging (CMR) is important for the prognosis of heart failure (HF). Herein, we aimed to identify the characteristics and prognostic value of strain analysis revealed by CMR in different HF phenotypes. Methods: Participants with HF, including HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction, and controls were enrolled. The baseline information and clinical parameters of participants were collected, and echocardiography and CMR examination were performed. Three-dimensional strain analysis was performed in the left ventricle, right ventricle, left atrium, and right atrium using CMR. A multifactor Cox risk proportional model was established to assess the influencing factors of cardiovascular adverse events in patients with HF. Results: During a median follow-up of 999 days (range: 616-1334), 20.6% of participants (73/354) experienced adverse events (HF readmission and/or cardiovascular death). Univariable Cox regression revealed that a 1% increase in left atrial global longitudinal strain (LAGLS) was associated with a hazard ratio (HR) of 1.21 [95% confidence interval (CI):1.15-1.28; P < 0.001]. Left ventricular global circumferential strain (LVGCS) (HR, 1.18; 95% CI: 1.12-1.24; P < 0.001), and left ventricular global longitudinal strain (LVGLS) (HR, 1.27; 95% CI: 1.20-1.36; P < 0.001) were also associated with HF hospitalizations and cardiovascular deaths. Among clinical variables, hypertension (HR, 2.11; 95% CI: 1.33-13.36; P = 0.002), cardiomyopathy (HR, 2.26; 95% CI: 1.42-3.60; P < 0.001) were associated with outcomes in univariable analysis. Multivariable analyses revealed that LAGLS (95% CI: 1.08-1.29; P < 0.001), LVGLS (95% CI:1.08-1.29; P < 0.001) and LVGCS (95% CI: 1.19-1.51; P < 0.001) were significantly associated with outcomes. Among clinical variables, hypertension (95% CI: 1.09-3.73; P < 0.025) remained a risk factor. Conclusion: CMR plays an obvious role in phenotyping HF. Strain analysis, particularly left atrial and left ventricular strain analysis (LAGLS, LVGLS, and LVGCS) has good value in predicting adverse outcome events.

Protective effect of 8-Gingerol, a potent constituent of ginger, on acute lung injury following hemorrhagic shock in rats.

Acute lung injury (ALI) is a common complication after hemorrhagic shock (HS), which is associated with HS-induced inflammatory response, oxidative stress, and cell apoptosis. This study aimed to investigate the therapeutic efficacy of 8-Gingerol, a constituent extracted from ginger, on ALI after HS in rats. We established a fixed press hemorrhage model in SD rats, in which the HS rats were administered 15 or 30 mg/kg of 8-Gingerol by intraperitoneal injection before fluid resuscitation. H&E staining and TUNEL staining were performed to evaluate histopathological changes and cell apoptosis in lung tissues, respectively. Quantitative reverse transcription PCR and Western blot were used to measure gene and protein expression. Pro-inflammatory cytokines were detected by ELISA kits. Immunofluorescence of myeloperoxidase was used to evaluate neutrophil infiltration. 8-Gingerol reduced pulmonary edema, alveolar wall thickness, and cell apoptosis in lung tissues of HS rats. Regarding inflammatory responses, 8-Gingerol attenuated neutrophil infiltration in lung tissues, reduced pro-inflammatory cytokines in lung tissues and bronchoalveolar lavage fluid, and decreased the levels of NLRP3, ASC, and cleaved caspase 1 in lung tissues. Additionally, 8-Gingerol ameliorated oxidative stress in lung tissues as evidenced by increased antioxidant indicators (SOD and GSH) and decreased production of MDA and ROS. The therapeutic effects of 8-Gingerol were associated with the regulation of MAPK and Nrf2/HO-1 pathways. These results support 8-Gingerol as a promising drug for the treatment of HS-induced ALI.

Exosomal miR-1202 mediates Brodmann Area 44 functional connectivity changes in medication-free patients with major depressive disorder: An fMRI study.

Previous large-sample postmortem study revealed that the expression of miR-1202 in brain tissues from Brodmann area 44 (BA44) was dysregulated in patients with major depressive disorder (MDDs). However, the specific in vivo neuropathological mechanism of miR-1202 as well as its interplay with BA44 circuits in the depressed brain are still unclear. Here, we performed a case-control study with imaging-genetic approach based on resting-state functional magnetic resonance imaging (MRI) data and miR-1202 quantification from 110 medication-free MDDs and 102 healthy controls. Serum-derived circulating exosomes that readily cross the blood-brain barrier were isolated to quantify miR-1202. For validation, repeated MR scans were performed after a six-week follow-up of antidepressant treatment on a cohort of MDDs. Voxelwise factorial analysis revealed two brain areas (including the striatal-thalamic region) in which the effect of depression on the functional connectivity with BA44 was significantly dependent on the expression level of exosomal miR-1202. Moreover, longitudinal change of the BA44 connectivity with the striatal-thalamic region in MDDs after antidepressant treatment was found to be significantly related to the level of miR-1202 expression. These findings revealed that the in vivo neuropathological effect of miR-1202 dysregulation in depression is possibly exerted by mediating neural functional abnormalities in BA44-striatal-thalamic circuits.

Characterisation, corrosion resistance and in vitro bioactivity of manganese-doped hydroxyapatite films electrodeposited on titanium.

This work elucidated the corrosion resistance and in vitro bioactivity of electroplated manganese-doped hydroxyapatite (MnHAp) film on NaOH-treated titanium (Ti). The NaOH treatment process was performed on Ti surface to enhance the adhesion of the MnHAp coating on Ti. Scanning electron microscopy images showed that the MnHAp coating had needle-like apatite crystals, and the approximately 10 µm thick layer was denser than HAp. Energy-dispersive X-ray spectroscopy analysis revealed that the MnHAp crystals were Ca-deficient and the Mn/P molar ratio was 0.048. X-ray diffraction confirmed the presence of single-phase MnHAp, which was aligned vertically to the substrate. Fourier transform infrared spectroscopy indicated the presence of phosphate bands ranging from 500 to 650 and 900 to 1,100 cm(-1), and a hydroxyl band at 3,571 cm(-1), which was characteristic of HAp. Bond strength test revealed that adhesion for the MnHAp coating was more enhanced than that of the HAp coating. Potentiodynamic polarisation test showed that the MnHAp-coated surface exhibited superior corrosion resistance over the HAp single-coated surface. Bioactivity test conducted by immersing the coatings in simulated body fluid showed that MnHAp coating can rapidly induce bone-like apatite nucleation and growth. Osteoblast cellular tests revealed that the MnHAp coating was better at improving the in vitro biocompatibility of Ti than the HAp coating.

[Preparation of chitosan/strontium-substituted hydroxyapatite films on titanium and its FTIR characteristics].

Chitosan/strontium-substituted hydroxyapatite (CHI/SrHAP) coatings were prepared on titanium substrate by electrochemical deposition technique containing Sr2+, Ca2+, PO4(3-) and Chitosan. The as-prepared coatings were examined by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) tests. The results indicate that the CHI/SrHAP coatings take the morphology of flake-like rather than the needle-like crystal , and the composite coating becomes more compact. The FTIR test indicates that the typical vibration absorption peaks of chitosan (amide I and amide II) emerged, simulated body fluid immersion test proved that the CHI/SrHAP coatings had induced carbonate-apatite formation, indicating that the composite coating possesses excellent biocompatibility. In the electrochemical corrosion testing, that the CHI/SrHAP coatings showed stronger corrosion resistance than pure Ti.

The Diagnostic and Prognostic Value of Cardiac Magnetic Resonance Strain Analysis in Heart Failure with Preserved Ejection Fraction.

Background: Strain analysis of cardiac magnetic resonance (CMR) is critical for the diagnosis and prognosis of heart failure (HF) with preserved ejection fraction (HFpEF). Our study aimed to identify the diagnostic and prognostic value of strain analysis revealed by CMR in HFpEF. Methods: Participants in HFpEF and control were recruited according to the guideline. Baseline information, clinical parameters, blood samples were collected, and echocardiography and CMR examination were performed. Various parameters, including global longitudinal strain, global circumferential strain (GCS) and global radial strain in left ventricle (LV), right ventricle (RV), and left atrium, were measured from CMR. Receiver operator curve (ROC) was established to evaluate the diagnostic and prognostic value of strains in HFpEF. Results: Seven strains, with the exception of RVGCS, were employed to generate ROC curves after t-test. All strains had significant diagnostic value for HFpEF. The area under curve (AUC) of LV strains was greater than 0.7 and the AUC of the combined analysis of LV strains was 0.858 (95% confidence interval (CI): 0.798-0.919, sensitivity: 0.713, specificity: 0.875, P < 0.001), indicating that they had a higher diagnostic value than individual LV strains. However, individual strains had no predictive value in identifying end-point events in HFpEF, the AUC of coanalysis of LV strains was 0.722 (95% CI: 0.573-0.872, sensitivity: 0.500, specificity: 0.959, P = 0.004), indicating its prognostic relevance. Conclusion: Individual strain analysis in CMR may be useful for diagnosing HFpEF, the combination of LV strain analysis had the highest diagnostic value. Moreover, the prognostic value of individual strain analysis in predicting HFpEF outcome was not satisfactory while the combined usage of LV strain analysis was prognostically valuable in HFpEF outcome prediction.

METTL14 Suppresses Tumor Stemness and Metastasis of Colon Cancer Cells by Modulating m6A-Modified SCD1.

Colon cancer (CC) is a malignant disease of the digestive tract, and its rising prevalence poses a grave threat to people's health. N6-methyladenosine (m6A) modification is essential for various crucial life processes through modulating gene expression. Methyltransferase-like 14 (METTL14), the m6A methylation transferase core protein, and its aberrant expression is intimately correlated to tumor development. This study was conducted to probe the impacts and specific mechanisms of METTL14 on the biological process of CC. Bioinformatics data disclosed that METTL14 was significantly attenuated in CC. Functional assays were executed to ascertain how METTL14 affected CC tumorigenicity, and METTL14 overexpression caused a notable decline in viability, migration, invasion, and stemness phenotype of CC cells. Then, in-depth mechanistic studies displayed that stearoyl-CoA desaturase 1 (SCD1) was a downstream target gene of METTL14-mediated m6A modification. METTL14 overexpression substantially augmented the m6A modification of SCD1 mRNA and diminished the SCD1 mRNA level. In addition, we revealed that YTHDF2 was the m6A reader to recognize METTL14 m6A-modified SCD1 mRNA and abolish its stability. Finally, we also validated that METTL14 might impede the tumorigenic process of CC through SCD1 mediated Wnt/ß-catenin signaling. Taken together, this study presented that METTL14 performed as a potential therapeutic target in CC with important implications for the prognosis amelioration of CC patients.

Serum exosomal hsa_circRNA_0001842 is the potential biomarker for diagnosing lower limb vascular disease in type 2 diabetes mellitus.

This study aimed to identify the potential circular RNAs (circRNAs) in exosomes isolated from serum as biomarkers of lower limb vascular disease (LLVD) in patients with type 2 diabetes mellitus (T2DM). This research collected circRNAs from exosomes isolated from three T2DM patients and three T2DM patients with LLVD for microarray analysis. Five candidate biomarkers derived from differentially expressed circRNAs were then validated by quantitative real-time polymerase chain reaction in 20 T2DM patients and 20 T2DM patients with LLVD. Finally, expression levels of circRNAs were validated in 160 samples. Significant differences in the expression of 295 circRNAs were found between T2DM controls and T2DM patients with LLVD. Among them, 191 differentially expressed circRNAs were upregulated, and 104 were downregulated in T2DM patients with LLVD. Three upregulated and two downregulated circRNAs were further confirmed in 40 samples. According to the testing of 160 samples, hsa_circ_0001842 showed a noticeable specificity in the T2DM patients with LLVD group (n = 80), with an area under the curve (AUC) of 0.79, a sensitivity of 88.75%, and a specificity of 68.75%. In conclusion, hsa_circ_0001842 was found as a potential diagnostic biomarker for T2DM with LLVD.

Chlamydia psittaci pneumonia in Wuxi, China: retrospective analysis of 55 cases and predictors of severe disease.

Purpose: More and more patients with community-acquired pneumonia have been detected with Chlamydia psittaci (C. psittaci) infected using metagenomic next-generation sequencing (mNGS). Previously, this was unheard of, and several patients presented with severe pneumonia and even required ECMO. We aimed to clarify the clinical characteristics of C. psittaci pneumonia and find out if there are any possible predictors of severe C. psittaci pneumonia. Methods: In this retrospective study, we included all confirmed cases of C. psittaci pneumonia in Wuxi. Epidemiological, clinical, and radiological features, as well as laboratory data, were collected and analyzed. Results: We enrolled 55 patients with C. psittaci pneumonia, with 30 (54.5%) having a history of exposure to birds or their internal organs. 50 (90.9%) patients were diagnosed by mNGS. Patients with C. psittaci pneumonia had many complications, among which, that deserve sufficient attention from clinicians were vascular embolic events (3, 5.5%). High fever was the most common clinical manifestation (41, 74.5%). The majority of patients had a significant increase in neutrophils ratio, neutrophils to lymphocytes ratio (NLR), rapid c-reactive protein, creatine kinase (CK), and lactate dehydrogenase (LDH), as well as a decrease in lymphocytes ratio, albumin, serum sodium, serum potassium, and serum phosphorus. Chest computed tomography scans revealed unilateral pneumonia (70.9%), consolidation (87.3%), air bronchogram (76.4%), and ground-glass opacity (69.1%). The neutrophil ratio, NLR, LDH, and CK were all factors that could identify severe pneumonia. Both AUCs exceeded 0.8; the respective 95% CIs were 0.715-0.944, 0.710-0.963, 0.677-0.937, and 0.718-0.950; all p < 0.05 (0.01, 0.001, 0.007, 0.007 respectively). The ORs were 10.057, 9.750, 10.057, and 9.667, respectively; the 95% CIs were 2.643-38.276, 2.339-40.649, and 2.643-38.276, respectively; all p-values were less than 0.05 (0.001, 0.002, 0.001, 0.001 respectively). Conclusion: C. psittaci pneumonia is a very complex disease that changes all the time. Some patients showed severe pneumonia. Patients will have a poor prognosis if they are not treated promptly and effectively. We discovered that many clinical indicators were typical. Meanwhile, significant increases in neutrophil ratio, NLR, LDH, and CK predicted severe pneumonia. Timely detection of mNGS provided substantial help for clinical diagnosis and early treatment.