Predicting Chronic Myocardial Ischemia Using CCTA-Based Radiomics Machine Learning Nomogram.

BACKGROUND: Coronary computed tomography angiography (CCTA) is a well-established non-invasive diagnostic test for the assessment of coronary artery diseases (CAD). CCTA not only provides information on luminal stenosis but also permits non-invasive assessment and quantitative measurement of stenosis based on radiomics. PURPOSE: This study is aimed to develop and validate a CT-based radiomics machine learning for predicting chronic myocardial ischemia (MIS). METHODS: CCTA and SPECT-myocardial perfusion imaging (MPI) of 154 patients with CAD were retrospectively analyzed and 94 patients were diagnosed with MIS. The patients were randomly divided into two sets: training (n = 107) and test (n = 47). Features were extracted for each CCTA cross-sectional image to identify myocardial segments. Multivariate logistic regression was used to establish a radiomics signature after feature dimension reduction. Finally, the radiomics nomogram was built based on a predictive model of MIS which in turn was constructed by machine learning combined with the clinically related factors. We then validated the model using data from 49 CAD patients and included 18 MIS patients from another medical center. The receiver operating characteristic curve evaluated the diagnostic accuracy of the nomogram based on the training set and was validated by the test and validation set. Decision curve analysis (DCA) was used to validate the clinical practicability of the nomogram. RESULTS: The accuracy of the nomogram for the prediction of MIS in the training, test and validation sets was 0.839, 0.832, and 0.816, respectively. The diagnosis accuracy of the nomogram, signature, and vascular stenosis were 0.824, 0.736 and 0.708, respectively. A significant difference in the number of patients with MIS between the high and low-risk groups was identified based on the nomogram (P < .05). The DCA curve demonstrated that the nomogram was clinically feasible. CONCLUSION: The radiomics nomogram constructed based on the image of CCTA act as a non-invasive tool for predicting MIS that helps to identify high-risk patients with coronary artery disease.

Role of contacts in long-range protein conductance.

Proteins are widely regarded as insulators, despite reports of electrical conductivity. Here we use measurements of single proteins between electrodes, in their natural aqueous environment to show that the factor controlling measured conductance is the nature of the electrical contact to the protein, and that specific ligands make highly selective electrical contacts. Using six proteins that lack known electrochemical activity, and measuring in a potential region where no ion current flows, we find characteristic peaks in the distributions of measured single-molecule conductances. These peaks depend on the contact chemistry, and hence, on the current path through the protein. In consequence, the measured conductance distribution is sensitive to changes in this path caused by ligand binding, as shown with streptavidin-biotin complexes. Measured conductances are on the order of nanosiemens over distances of many nanometers, orders of magnitude more than could be accounted for by electron tunneling. The current is dominated by contact resistance, so the conductance for a given path is independent of the distance between electrodes, as long as the contact points on the protein can span the gap between electrodes. While there is no currently known biological role for high electronic conductance, its dependence on specific contacts has important technological implications, because no current is observed at all without at least one strongly bonded contact, so direct electrical detection is a highly selective and label-free single-molecule detection method. We demonstrate single-molecule, highly specific, label- and background free-electronic detection of IgG antibodies to HIV and Ebola viruses.

Radiological model based on the standard magnetic resonance sequences for detecting methylguanine methyltransferase methylation in glioma using texture analysis.

This study aims to build a radiological model based on standard MR sequences for detecting methylguanine methyltransferase (MGMT) methylation in gliomas using texture analysis. A retrospective cross-sectional study was undertaken in a cohort of 53 glioma patients who underwent standard preoperative magnetic resonance (MR) imaging. Conventional visual radiographic features and clinical factors were compared between MGMT promoter methylated and unmethylated groups. Texture analysis extracted the top five most powerful texture features of MR images in each sequence quantitatively for detecting the MGMT promoter methylation status. The radiomic signature (Radscore) was generated by a linear combination of the five features and estimates in each sequence. The combined model based on each Radscore was established using multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve, nomogram, calibration, and decision curve analysis (DCA) were used to evaluate the performance of the model. No significant differences were observed in any of the visual radiographic features or clinical factors between different MGMT methylated statuses. The top five most powerful features were selected from a total of 396 texture features of T1, contrast-enhanced T1, T2, and T2 FLAIR. Each sequence's Radscore can distinguish MGMT methylated status. A combined model based on Radscores showed differentiation between methylated MGMT and unmethylated MGMT both in the glioblastoma (GBM) dataset as well as the dataset for all other gliomas. The area under the ROC curve values for the combined model was 0.818, with 90.5% sensitivity and 72.7% specificity, in the GBM dataset, and 0.833, with 70.2% sensitivity and 90.6% specificity, in the overall gliomas dataset. Nomogram, calibration, and DCA also validated the performance of the combined model. The combined model based on texture features could be considered as a noninvasive imaging marker for detecting MGMT methylation status in glioma.

Predicting the progression of Parkinson's disease using conventional MRI and machine learning: An application of radiomic biomarkers in whole-brain white matter.

PURPOSE: This study aimed to develop and validate a radiomics model based on whole-brain white matter and clinical features to predict the progression of Parkinson disease (PD). METHODS: PD patient data from the Parkinson's Progress Markers Initiative (PPMI) database was evaluated. Seventy-two PD patients with disease progression, as measured by the Hoehn-Yahr Scale (HYS) (stage 1-5), and 72 PD patients with stable PD were matched by sex, age, and category of HYS and included in the current study. Each individual's T1 -weighted MRI scans at the baseline timepoint were segmented to isolate whole-brain white matter for radiomics feature extraction. The total dataset was divided into a training and test set according to subject serial number. The size of the training dataset was reduced using the maximum relevance minimum redundancy (mRMR) algorithm to construct a radiomics signature using machine learning. Finally, a joint model was constructed by incorporating the radiomics signature and clinical progression scores. The test data were then used to validate the prediction models, which were evaluated based on discrimination, calibration, and clinical utility. RESULTS: Based on the overall data, the areas under curve (AUCs) of the joint model, signature and Unified Parkinson Disease Rating Scale III PD rating score were 0.836, 0.795, and 0.550, respectively. Furthermore, the sensitivities were 0.805, 0.875, and 0.292, respectively, and the specificities were 0.722, 0.697, and 0.861, respectively. In addition, the predictive accuracy of the model was 0.827, the sensitivity was 0.829 and the specificity was 0.702 for stage-1 PD. For stage-2 PD, the predictive accuracy of the model was 0.854, the sensitivity was 0.960, and the specificity was 0.600. CONCLUSION: Our results provide evidence that conventional structural MRI can predict the progression of PD. This work also supports the use of a simple radiomics signature built from whole-brain white matter features as a useful tool for the assessment and monitoring of PD progression.

Metformin restores hippocampal neurogenesis and learning and memory via regulating gut microbiota in the obese mouse model.

Numerous studies have shown that over-nutritional obesity may lead to pre-diabetes, type 2 diabetes and cognitive decline. As the degree of metabolic disorders increases, the cognitive decline is getting worse. However, the cellular events that cause this cognitive dysfunction is yet to be clarified. We used a high-fat diet (HFD) consumption-induced obesity mouse model to test the effects of metformin on the hippocampal neurogenesis and learning and memory abilities of obese mice. 5-Bromo-2'-deoxyuridine (BrdU) labelling and retrovirus labeling were applied to detect hippocampal newborn neurons. Behavioral experiments were used to detect learning and memory abilities of mice. 16S rRNA gene sequencing was performed to detect the composition of gut microbiota. The positron emission tomography (PET) was conducted to detect the energy metabolism activity of different mouse brain regions. Our results reveal that metformin restores the impairment of neurogenesis in the dentate gyrus and finally prevents the cognitive decline of the obese mice. Moreover, the therapeutic effects of metformin are achieved by regulating the composition of gut microbiota of mice, which may inhibit microglia activation and neuroinflammation in the brain of obese mice. This study suggests that metformin may be taken as a promising candidate for the intervention of cognitive decline related to imbalance of gut microbiota caused by obesity.

A comparative analysis between low-dose-rate brachytherapy and external beam radiation therapy for low- and intermediate-risk prostate cancer in Asian men.

OBJECTIVE: To report the long-term clinical outcomes of low-risk (LR) and intermediate-risk (IR) prostate cancer patients treated with low-dose-rate brachytherapy (LDR-BT) and external beam radiation therapy (EBRT). PATIENTS AND METHODS: Men with biopsy-proven low- and intermediate-risk prostate cancer received EBRT and LDR-BT in an Asian academic center from 2000 to 2019 were reviewed. Kaplan-Meier survival analysis was performed to compare biochemical failure-free survival (bFFS) and overall survival (OS) between LDR and EBRT in the low- and intermediate-risk cohorts. RESULTS: 642 patients (521 EBRT and 121 LDR-BT) with low- and intermediate-risk prostate cancer were included for analysis. In the intermediate-risk group, 5- and 10-year bFFS was 96%, 89% and 86%, 61% for LDR-BT and EBRT, respectively. LDR-BT was associated with a statistically significant improvement of bFFS in the intermediate-risk cohort (HR 2.7, p = 0.02). In the low-risk cohort, no difference of bFFS was found between LDR-BT and EBRT (HR 1.9, p = 0.08). Hormone therapy was more common in EBRT than LDR-BT for intermediate-risk group (71% versus 44%, p < 0.05). Prostate cancer-specific mortality was low in both EBRT (1%) and LDR-BT (2%) cohorts. No significant difference in OS was found between LDR-BT and EBRT in low- and intermediate-risk group (HR 2.1, p = 0.2 and HR = 1.7, p = 0.3). CONCLUSION: In our retrospective study, LDR-BT is associated with superior bFFS compared with EBRT in Asian men with intermediate-risk prostate cancer.

Correcting abnormalities in miR-124/PTPN1 signaling rescues tau pathology in Alzheimer's disease.

MicroRNAs have been implicated in diverse physiological and pathological processes. We previously reported that aberrant microRNA-124 (miR-124)/non-receptor-type protein phosphatase 1 (PTPN1) signaling plays an important role in the synaptic disorders associated with Alzheimer's disease (AD). In this study, we further investigated the potential role of miR-124/PTPN1 in the tau pathology of AD. We first treated the mice with intra-hippocampal stereotactic injections. Then, we used quantitative real-time reverse transcription PCR (qRT-PCR) to detect the expression of microRNAs. Western blotting was used to measure the level of PTPN1, the level of tau protein, the phosphorylation of tau at AD-related sites, and alterations in the activity of glycogen synthase kinase 3ß (GSK-3ß) and protein phosphatase 2 (PP2A). Immunohistochemistry was also used to detect changes in tau phosphorylation levels at AD-related sites and somadendritic aggregation. Soluble and insoluble tau protein was separated by 70% formic acid (FA) extraction to examine tau solubility. Finally, behavioral experiments (including the Morris water maze, fear conditioning, and elevated plus maze) were performed to examine learning and memory ability and emotion-related behavior. We found that artificially replicating the abnormalities in miR-124/PTPN1 signaling induced AD-like tau pathology in the hippocampus of wild-type mice, including hyperphosphorylation at multiple sites, insolubility and somadendritic aggregation, as well as learning/memory deficits. We also found that disruption of miR-124/PTPN1 signaling was caused by the loss of RE1-silencing transcription factor protein, which can be initiated by Aß insults or oxidative stress, as observed in the brains of P301S mice. Correcting the deregulation of miR-124/PTPN1 signaling rescued the tau pathology and learning/memory impairments in the P301S mice. We also found that miR-124/PTPN1 abnormalities induced activation of glycogen synthase kinase 3 (GSK-3) and inactivation of protein phosphatase 2A (PP2A) by promoting tyrosine phosphorylation, implicating an imbalance in tau kinase/phosphatase. Thus, targeting the miR-124/PTPN1 signaling pathway is a promising therapeutic strategy for AD.

Radiomics nomogram based on MRI for predicting white matter hyperintensity progression in elderly adults.

BACKGROUND: White matter hyperintensity (WMH) is widely observed in aging brain and is associated with various diseases. A pragmatic and handy method in the clinic to assess and follow up white matter disease is strongly in need. PURPOSE: To develop and validate a radiomics nomogram for the prediction of WMH progression. STUDY TYPE: Retrospective. POPULATION: Brain images of 193 WMH patients from the Picture Archiving and Communication Systems (PACS) database in the A Medical Center (Zhejiang Provincial People's Hospital). MRI data of 127 WMH patients from the PACS database in the B Medical Center (Zhejiang Lishui People's Hospital) were included for external validation. All of the patients were at least 60 years old. FIELD STRENGTH/SEQUENCE: T1 -fluid attenuated inversion recovery images were acquired using a 3T scanner. ASSESSMENT: WMH was evaluated utilizing the Fazekas scale based on MRI. WMH progression was assessed with a follow-up MRI using a visual rating scale. Three neuroradiologists, who were blinded to the clinical data, assessed the images independently. Moreover, interobserver and intraobserver reproducibility were performed for the regions of interest for segmentation and feature extraction. STATISTICAL TESTS: A receiver operating characteristic (ROC) curve, the area under the curve (AUC) of the ROC was calculated, along with sensitivity and specificity. Also, a Hosmer-Lemeshow test was performed. RESULTS: The AUC of radiomics signature in the primary, internal validation cohort, external validation cohort were 0.886, 0.816, and 0.787, respectively; the specificity were 71.79%, 72.22%, and 81%, respectively; the sensitivity were 92.68%, 87.94% and 78.3%, respectively. The radiomics nomogram in the primary cohort (AUC = 0.899) and the internal validation cohort (AUC = 0.84). The Hosmer-Lemeshow test showed no significant difference between the primary cohort and the internal validation cohort (P > 0.05). The AUC of the radiomics nomogram, radiomics signature, and hyperlipidemia in all patients from the primary and internal validation cohort was 0.878, 0.848, and 0.626, respectively. DATA CONCLUSION: This multicenter study demonstrated the use of a radiomics nomogram in predicting the progression of WMH with elderly adults (an age of at least 60 years) based on conventional MRI. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:535-546.

Development of a Novel Multiparametric MRI Radiomic Nomogram for Preoperative Evaluation of Early Recurrence in Resectable Pancreatic Cancer.

BACKGROUND: In pancreatic cancer, methods to predict early recurrence (ER) and identify patients at increased risk of relapse are urgently required. PURPOSE: To develop a radiomic nomogram based on MR radiomics to stratify patients preoperatively and potentially improve clinical practice. STUDY TYPE: Retrospective. POPULATION: We enrolled 303 patients from two medical centers. Patients with a disease-free survival ≤12 months were assigned as the ER group (n = 130). Patients from the first medical center were divided into a training cohort (n = 123) and an internal validation cohort (n = 54). Patients from the second medical center were used as the external independent validation cohort (n = 126). FIELD STRENGTH/SEQUENCE: 3.0T axial T1 -weighted (T1 -w), T2 -weighted (T2 -w), contrast-enhanced T1 -weighted (CET1 -w). ASSESSMENT: ER was confirmed via imaging studies as MRI or CT. Risk factors, including clinical stage, CA19-9, and radiomic-related features of ER were assessed. In addition, to determine the intra- and interobserver reproducibility of radiomic features extraction, the intra- and interclass correlation coefficients (ICC) were calculated. STATISTICAL TESTS: The area under the receiver-operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and test groups. The results of decision curve analysis (DCA) indicated that the radiomic nomogram achieved the most net benefit. RESULTS: The AUC values of ER evaluation for the radiomics signature were 0.80 (training cohort), 0.81 (internal validation cohort), and 0.78 (external validation cohort). Multivariate logistic analysis identified the radiomic signature, CA19-9 level, and clinical stage as independent parameters of ER. A radiomic nomogram was then developed incorporating the CA19-9 level and clinical stage. The AUC values for ER risk evaluation using the radiomic nomogram were 0.87 (training cohort), 0.88 (internal validation cohort), and 0.85 (external validation cohort). DATA CONCLUSION: The radiomic nomogram can effectively evaluate ER risks in patients with resectable pancreatic cancer preoperatively, which could potentially improve treatment strategies and facilitate personalized therapy in pancreatic cancer. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;52:231-245.

[Application Values of Gadolinium-ethoxybenzyl Diethylenetriaminepentaacetic Acid Enhanced Magnetic Resonance Imaging-based Radiomics in the Quantitative Assessment of Liver Reserve Function of Patients with Liver Cirrhosis].

Objective To evaluate the correlation between the radiomics signature of hepatobiliary phase imaging of gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid(Gd-EOB-DTPA)enhanced magnetic resonance imaging(MRI)and Child-Pugh of liver cirrhosis,establish nomogram prediction model,and assess the predictive value of quantitative assessment of liver reserve function of patients with liver cirrhosis. Methods One hundred patients with liver cirrhosis who met the inclusion criteria were divided into 52 patients with Child-Pugh grade A and 48 patients with Child-Pugh grade B+C according to Child-Pugh classification criteria,and were randomly divided into training set and test set at a proportion of 7∶3.The AK software was used to extract the imaging features of the Gd-EOB-DTPA-enhanced MRI hepatobiliary images of the patients in the training set,and the least absolute shrinkage and selection operator feature selection algorithm was used to reduce the dimension of the data,select the features,and construct the radiomics tags.According to the radiomics label Rad-score,a line chart(nomogram)prediction model was established to predict the Child-Pugh B+C level of liver reserve function.The model was applied to the training set and test set respectively,and the diagnostic efficiency was quantitatively evaluated by receiver operating characteristic(ROC)curve. Results After dimension reduction and screening of 396 texture feature parameters extracted by AK software,7 image feature parameters were obtained.According to the above characteristics,the radiomics tag Rad-score was constructed and the nomogram prediction model was created.The differences of Rad-score scores between Child-Pugh A and Child-Pugh B+C groups in training set and test set were statistically analyzed by Wilcoxon rank sum test(P=0.000, P=0.001).The diagnostic efficacy of nomogram prediction model for predicting Child-Pugh B+C grade of liver reserve function in the ROC curve of training set and test set was 0.88 and 0.86 respectively. Conclusions The nomogram prediction model created according to the radiomics tag Rad-score of patients with liver cirrhosis with different liver reserve functions can be used as a more accurate and reliable auxiliary detection tool for liver reserve function.It provides a new means for clinicians to evaluate liver reserve function more accurately.

Defining early events of Epstein-Barr virus (EBV) infection in immortalized nasopharyngeal epithelial cells using cell-free EBV infection.

Epstein-Barr virus (EBV) infection is strongly associated with nasopharyngeal carcinoma, a common cancer in Southeast Asia and certain regions of Africa. However, the dynamics of EBV episome maintenance in infected nasopharyngeal epithelial (NPE) cells remain largely undefined. Here, we report the establishment of a highly efficient cell-free EBV infection method for NPE cells. By using this method, we have defined some of the dynamic events involved in the early stage of EBV infection in NPE cells. We report, for the first time, a rapid loss of EBV copies from infected NPE cells during the first 12-72 h post-infection. The rate of EBV loss slowed at later stages of infection. Live cell imaging revealed that the freshly infected NPE cells were delayed in entry into mitosis compared with uninfected cells. Freshly infected NPE cells transcribed significantly higher levels of lytic EBV genes BZLF1 and BMRF1 yet significantly lower levels of EBER1/2 than stably infected NPE cells. Notably, there were very low or undetectable levels of protein expressions of EBNA1, LMP1, Zta and Rta in freshly infected NPE cells, whereas EBNA1 and LMP1 proteins were readily detected in stable EBV-infected NPE cells. The kinetics of EBV loss and the differential EBV gene expression profiles between freshly and stably infected NPE cells are in line with the suggestion of epigenetic changes in the EBV genome that affect viral gene expression and the adaptation of host cells to EBV infection to maintain persistent EBV infection in NPE cells.

The Role of Iron Competition in the Antagonistic Action of the Rice Endophyte Streptomyces sporocinereus OsiSh-2 Against the Pathogen Magnaporthe oryzae.

Rice blast caused by Magnaporthe oryzae severely impacts global rice yield stability. The rice endophyte Streptomyces sporocinereus OsiSh-2, with strong antagonistic activity towards M. oryzae, has been reported in our previous study. To decipher the model of the antagonistic action of OsiSh-2 towards M. oryzae, we compared the iron-capturing abilities of these two strains. The cultivation of OsiSh-2 and a M. oryzae strain under iron-rich and iron-starved conditions showed that M. oryzae depended more on iron supplementation for growth and development than did OsiSh-2. Genomic analysis of the S. sporocinereus and M. oryzae species strains revealed that they might possess different iron acquisition strategies. The actinobacterium OsiSh-2 is likely to favor siderophore utilization compared to the fungus M. oryzae. In addition, protein annotations found that OsiSh-2 contains the highest number of the siderophore biosynthetic gene clusters among the 13 endophytic actinomycete strains and 13 antifungal actinomycete strains that we compared, indicating the prominent siderophore production potential of OsiSh-2. Additionally, we verified that OsiSh-2 could excrete considerably more siderophores than Guy11 under iron-restricted conditions and displayed greater Fe3+-reducing activity during iron-supplemental conditions. Measurements of the iron mobilization between the antagonistic OsiSh-2 and Guy11 showed that the iron concentration is higher around OsiSh-2 than around Guy11. In addition, adding iron near OsiSh-2 could decrease the antagonism of OsiSh-2 towards Guy11. Our study revealed that the antagonistic capacity displayed by OsiSh-2 towards M. oryzae was related to the competition for iron. The highly efficient iron acquisition system of OsiSh-2 may offer valuable insight for the biocontrol of rice blast.

Imbalance of intestinal immune function in piglets infected by porcine circovirus type 2 during the fetal period.

Porcine circovirus type 2- (PCV2-) associated reproductive disorders and enteritis have commonly been observed on PCV2-contaminated pig farms in recent years. In order to investigate disorders of intestinal immunity in piglets infected by PCV2 during the fetal period, 9 PCV2b-infected piglets and 6 non-infected piglets at one day of age were selected and euthanised prior to suckling. Samples of mesenteric lymph nodes (MLNs) and duodena were collected to investigate factors related to intestinal immunity and to detect lymphocytic apoptosis. The results indicated that there were no significant changes in the levels of IL-2, IL-10 and transforming growth factor-ß (TGF-ß) in the PCV2b-infected piglets but IFN-γ levels were significantly lower (P < 0.01) and IL-4 levels were significantly higher (P < 0.05) in infected piglets than in the controls. Furthermore, lymphocytic apoptosis increased in PCV2b-infected piglets and CD4+ to CD8+ ratios were lower in these piglets than in the controls. These findings suggest vertical transmission of PCV2b to fetuses, leading to an imbalance of intestinal immune function in piglets.

A Novel Mechanism of Spine Damages in Stroke via DAPK1 and Tau.

Synaptic spine loss is one of the major preceding consequences of stroke damages, but its underlying molecular mechanisms remain unknown. Here, we report that a direct interaction of DAPK1 with Tau causes spine loss and subsequently neuronal death in a mouse model with stroke. We found that DAPK1 phosphorylates Tau protein at Ser262 (pS(262)) in cortical neurons of stroke mice. Either genetic deletion of DAPK1 kinase domain (KD) in mice (DAPK1-KD(-/-)) or blocking DAPK1-Tau interaction by systematic application of a membrane permeable peptide protects spine damages and improves neurological functions against stroke insults. Thus, disruption of DAPK1-Tau interaction is a promising strategy in clinical management of stroke.

Silk Reconstitution Disrupts Fibroin Self-Assembly.

Using atomic force microscopy, we present the first molecular-scale comparison of two of the most important silk dopes, native (NSF) and reconstituted (RSF) silkworm fibroin. We found that both systems depended on shear to show self-assembly. Significant differences in the nature of self-assembly between NSF and RSF were shown. In the highest studied concentration of 1000 mg/L, NSF exhibited assembly into 20-30 nm-wide nanofibrils closely resembling the surface structures found in natural silk fibers. RSF, in contrast, showed no self-assembly whatsoever at the same concentration, which suggests that the reconstitution process significantly disrupts silk's inherent self-assembly capability. At lower concentrations, both RSF and NSF formed fibrils under shear, apparently denatured by the substrate. Using image analysis, we quantified the properties of these self-assembled fibrils as a function of concentration and found low-concentration fibrils of NSF to form larger continuous structures than those of RSF, further supporting NSF's superior self-assembly capabilities.

The biology of EBV infection in human epithelial cells.

EBV-associated human malignancies may originate from B cells and epithelial cells. EBV readily infects B cells in vitro and transforms them into proliferative lymphoblastoid cell lines. In contrast, infection of human epithelial cells in vitro with EBV has been difficult to achieve. The lack of experimental human epithelial cell systems for EBV infection has hampered the understanding of biology of EBV infection in epithelial cells. The recent success to infect human epithelial cells with EBV in vitro has allowed systematic investigations into routes of EBV entry, regulation of latent and lytic EBV infection, and persistence of EBV infection in infected epithelial cells. Understanding the biology of EBV infection in human epithelial cells will provide important insights to the role of EBV infection in the pathogenesis of EBV-associated epithelial malignancies including nasopharyngeal carcinoma and gastric carcinoma.

Time-series analysis of meteorological factors and emergency department visits due to dog/cat bites in Jinshan area, China.

Background: Meteorological factors play an important role in human health. Clarifying the occurrence of dog and cat bites (DCBs) under different meteorological conditions can provide key insights into the prevention of DCBs. Therefore, the objective of the study was to explore the relationship between meteorological factors and DCBs and to provide caution to avoid the incidents that may occur by DCBs. Methods: In this study, data on meteorological factors and cases of DCBs were retrospectively collected at the Shanghai Climate Center and Jinshan Hospital of Fudan University, respectively, in 2016-2020. The distributed lag non-linear and time series model (DLNM) were used to examine the effect of meteorological elements on daily hospital visits due to DCBs. Results: A total of 26,857 DCBs were collected ranging from 1 to 39 cases per day. The relationship between ambient temperature and DCBs was J-shaped. DCBs were positively correlated with daily mean temperature (rs = 0.588, P < 0.01). The relative risk (RR) of DCBs was associated with high temperature (RR = 1.450; 95% CI [1.220-1.722]). Female was more susceptible to high temperature than male. High temperature increased the risk of DCBs. Conclusions: The extremely high temperature increased the risk of injuries caused by DCBs, particularly for females. These data may help to develop public health strategies for potentially avoiding the occurrence of DCBs.

A novel disulfidptosis-related prognostic gene signature and experimental validation identify ACTN4 as a novel therapeutic target in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a prevalent form of malignancy globally. Disulfidptosis is novel programmed cell death pathway based on disulfide proteins, may have a positive impact on the development of LUAD treatment strategies. OBJECTIVE: To investigate the impact of disulfidptosis-related genes (DRGs) on the prognosis of LUAD, developed a risk model to facilitate the diagnosis and prognostication of patients. We also explored ACTN4 (DRGs) as a new therapeutic biomarker for LUAD. METHODS: We investigated the expression patterns of DRGs in both LUAD and noncancerous tissues. To assess the prognostic value of the DRGs, we developed risk models through univariate Cox analysis and lasso regression. The expression and function of ACTN4 was evaluated by qRT-PCR, immunohistochemistry and in vitro experiments. The TIMER examined the association between ACTN4 expression and immune infiltration in LUAD. RESULTS: Ten differentially expressed DRGs were identified. And ACTN4 was identified as potential risk factors through univariate Cox regression analysis (P< 0.05). ACTN4 expression and riskscore were used to construct a risk model to predict overall survival in LUAD, and high-risk demonstrated a significantly higher mortality rate compared to the low-risk cohort. qRT-PCR and immunohistochemistry assays indicated ACTN4 was upregulated in LUAD, and the upregulation was associated with clinicopathologic features. In vitro experiments showed the knockdown of ACTN4 expression inhibited the proliferation in LUAD cells. The TIMER analysis demonstrated a correlation between the expression of ACTN4 and the infiltration of diverse immune cells. Elevated ACTN4 expression was associated with a reduction in memory B cell count. Additionally, the ACTN4 expression was associated with m6A modification genes. CONCLUSIONS: Our study introduced a prognostic model based on DRGs, which could forecast the prognosis of patients with LUAD. The biomarker ACTN4 exhibits promise for the diagnosis and management of LUAD, given its correlation with tumor immune infiltration and m6A modification.

[Study on dietary patterns and its effect on infant health among left-behind children aged 1-4 years old with both parents working out in rural Anhui].

OBJECTIVE: To investigate dietary patterns of left-behind children aged 1-4 years old with both parents working out in rural Anhui, and to examine the relationship between dietary patterns and infant health. METHODS: In total, 424 left-behind children aged 1-4 years old were selected from 12 villages in 2 counties of Anhui province, 212 were both parents working out and 212 were both parents not working out. Infant dietary patterns were evaluated by a self-developed questionnaire, the reliability and validity were also assessed. Physical development, peripheral blood hemoglobin, traces elements of zinc, urinary iodine, infant neuropsychological development were evaluated. RESULTS: Infant dietary patterns in rural areas could be divided into 4 types, traditional type, animal protein-based type, nutrition-based type and beverage-based type. The prevalence of high score of nutrition type and animal protein-based type of infant dietary patterns in left-behind children were significant lower than those in control group. The prevalence of malnutrition, nutritional anemia, zinc deficiency, iodine deficiency in left-behind children with both parents working out were higher than those of control group (4.7%, 19.8%, 46.2%, 21.7% vs 0.9%, 8.5%, 34.4% and 12.7%) (P < 0.05). The prevalence of mental retardation and mental edge were significant higher in left-behind children than those of control group (3.8%, 20.8 vs 1.9%, 10.4%). Among left-behind children aged 1-4 years old with both parents working out in rural area, the prevalence of malnutrition was higher in infant with low score of traditional type dietary, the prevalence of obesity was higher in infant with high score of traditional type dietary (chi2 = 18.725, P = 0.002). The prevalence of nutritional anemia, zinc deficiency, mental retardation and mental edge were higher in infant with low scores of animal protein-based type and nutrition-based type dietary (P < 0.05). CONCLUSION: The feeding patterns of left-behind children aged 1-4 years old with both parents working out in rural were different to those with both parents not working out. Infant nutrition status was significantly associated with the intake frequency of traditional food. The prevalence of infant nutritional diseases and mental development were significantly associated with the intake frequency of animal protein-based food and nutrition-based food.

Prognostic Value and Potential Mechanism of MTFR2 in Lung Adenocarcinoma.

Mitochondrial fission regulator 2 (MTFR2) belongs to the MTFR1 family, which plays a crucial role in regulating oxidative phosphorylation. Recent studies indicate that it also participates in cancer carcinogenesis and development; however, the clinical significance of MTFR2 in lung adenocarcinoma has not been fully confirmed. Our current study investigated the relationships between clinical characteristics and MTFR2 expression based on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GSE31210) dataset, and clinical histopathological sample cohort. In addition, Kaplan-Meier and Cox regression analyses were additionally performed to evaluate the association between MTFR2 expression and patient survival. Gene set enrichment analysis (GESA) was conducted to spot possible pathways associated with MTFR2. Moreover, a single-sample GESA (ssGESA) was performed to evaluate the association between MTFR2 expression and immune cell infiltration. Cell colony formation assay, CCK-8 assay, cell cycle assay, and transwell assay were performed to verify the cell proliferation, migration, and invasion abilities after interfering with MTFR2 in lung cancer cells. Western blot assay was applied to identify the underlying protein levels. The results indicated that the elevated MTFR2 expression in lung adenocarcinoma samples correlated with T stage (P < 0.001), N stage (P = 0.005), M stage (P = 0.015), pathological stage (P = 0.002), and TP53 status (P < 0.001). Patients with a higher MTFR2 expression correlated with poorer overall survival (P < 0.01) and progression-free survival (P = 0.002). Knockdown of MTFR2 inhibited cell proliferation, migration, and invasion via AKT-cyclin D1 signaling and EMT pathways. Moreover, MTFR2 expression significantly positively correlated with Th2 cells (P < 0.001). Taken together, MTFR2 could serve as a novel prognostic indicator and therapeutic target for lung adenocarcinoma.