CircRNA_0044556 affects the sensitivity of triple-negative breast cancer cells to paclitaxel by regulating miR-665.

CircRNAs have been implicated in the development of resistance in triple-negative breast cancer (TNBC). However, the association between circRNA_0044556 and paclitaxel (PTX) resistance in TNBC is still limited. Therefore, the purpose of this study was to investigate the effect of circRNA_0044556 on biological function and PTX resistance in TNBC cells. PTX-resistant TNBC cells (MDA-MB-231/PTX) were obtained by continuously exposing MDA-MB-231 cells to increasing paclitaxel levels. The expression levels of circRNA_0044556 and miR-665 were measured by qRT-PCR. The regulatory relationship between miR-665 and circRNA_0044556 was verified by biological information website analysis and double-luciferase reporter gene detection experiments. MTT assay, clone assay, flow cytometry and Western blot analysis were used to evaluate the influence of cell biological function. Elevated circRNA_0044556 was observed in TNBC, and paclitaxel increased the expression of circRNA_0044556 in TNBC cells. In TNBC, circRNA_0044556 acted as a ceRNA for miR-665. In addition, low expression of circRNA_0044556 combined with miR-665 inhibited the proliferation of TNBC cells and paclitaxel-resistant TNBC cells while inducing cell death. Our study demonstrated that the downregulation of circRNA_0044556 inhibits the malignant progression of TNBC cells and paclitaxel resistance via miR-665. Thus, circRNA_0044556 may be a potential therapeutic target for PTX-resistance TNBC.

External Validation of the International IgA Nephropathy Prediction Tool in Older Adult Patients.

Purpose: The International IgA Nephropathy Prediction Tool (IIgAN-PT) can predict the risk of End-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50% for adult IgAN patients. Considering the differential progression between older adult and adult patients, this study aims to externally validate its performance in the older adult cohort. Patients and Methods: We analyzed 165 IgAN patients aged 60 and above from six medical centers, categorizing them by their predicted risk. The primary outcome was a ≥50% reduction in estimated glomerular filtration rate (eGFR) or kidney failure. Evaluation of both models involved concordance statistics (C-statistics), time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival curves, and calibration plots. Comparative reclassification was conducted using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: The study included 165 Chinese patients (median age 64, 60% male), with a median follow-up of 5.1 years. Of these, 21% reached the primary outcome. Both models with or without race demonstrated good discrimination (C-statistics 0.788 and 0.790, respectively). Survival curves for risk groups were well-separated. The full model without race more accurately predicted 5-year risks, whereas the full model with race tended to overestimate risks after 3 years. No significant reclassification improvement was noted in the full model without race (NRI 0.09, 95% CI: -0.27 to 0.34; IDI 0.003, 95% CI: -0.009 to 0.019). Conclusion: : Both models exhibited excellent discrimination among older adult IgAN patients. The full model without race demonstrated superior calibration in predicting the 5-year risk.

A study on post-traumatic stress disorder and post-traumatic growth among patients infected with COVID-19 in Wuhan.

Objective: The purpose of this study is to assess the physical and psychological conditions of hospitalized patients who were infected with COVID-19 in Wuhan, China, including post-traumatic stress disorder (PTSD) and post-traumatic growth (PTG) scores and predictors. Methods: The test group consisted of 102 hospitalized patients diagnosed with COVID-19 in Wuhan between March 4, 2020 and April 5, 2020, whereas the control group comprised 168 healthy study participants. Relevant information of the study participants was obtained using online questionnaires, covering five aspects-general information, physical state, emotional state, PTSD, and PTG. Results: In Wuhan, 37.3% of COVID-19-diagnosed hospitalized patients exhibited hyper-arousal symptoms of PTSD. This percentage is significantly higher than the 13.1% observed in the healthy population. Furthermore, the prevalence of PTG among the same group of hospitalized patients stood at 77.5%, surpassing the 66.1% rate found within the healthy population. It was determined that inconsistent sleep patterns during the hospitalization phase could be indicative of heightened vulnerability to hyperarousal symptoms of PTSD in COVID-19-diagnosed hospitalized patients. The study determined that inconsistent sleep patterns during hospitalization may be a predisposition factor that makes hospitalized patients diagnosed with covid-19 more susceptible to high arousal symptoms of post-traumatic stress disorder. Conversely, COVID-19-diagnosed hospitalized patients who maintained a tranquil demeanor and exhibited positive emotional perceptions during their hospitalization displayed reduced susceptibility to these PTSD symptoms. Factors such as possession of a bachelor's degree, history of severe acute respiratory syndrome (SARS) infection, and poor sleep patterns were identified as predictors elevating the risk of PTG. Whereas, a sentiment of happiness and consistent positive emotional perception during hospitalization were predictors of PTG. Intriguingly, a direct correlation was established between hyper-arousal symptoms of PTSD and PTG. Conclusion: Although the outbreak of COVID-19 has badly affected the physical and psychological well-being of patients, it has greatly enhanced their PTG.

Clinical characteristics and outcomes of pleural aspergillosis: a review of 13 cases.

Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), which mostly occurs in the immunocompromised host. The clinical condition is critical, especially to those who develop bronchopleural fistula. This study aimed to assess the characteristics and the prognosis of aspergillus pleurisy. Clinical data from 13 patients diagnosed with aspergillus pleurisy in our hospital from January 2000 to December 2022 were retrospectively studied. Thirteen patients with Aspergillus pleurisy were included. There were 10 males and 3 females, with a median age of 65 (range: 18-79) years. Bronchopleural fistula was present in eight patients. A proven diagnosis of Aspergillus pleurisy was based on positive pleural fluid culture in seven cases and histopathological examination of pleural biopsies in six cases. Four patients refused further treatment and were discharged from the hospital against medical advice. Nine cases recovered and were discharged after multiple antifungal treatments (systemic and topical antifungal therapies, pleural drainage and irrigation, and surgical repair). During follow-up, one patient, who suffered underlying bronchiectasis, died of massive hemoptysis 2 years after discharge. The remaining eight cases are still under close follow-up, with a median follow-up of 5.4 (range: 1.3-18.9) years. The prognosis of aspergillus pleurisy complicated with bronchopleural fistula is poor. Thoracic surgery, especially lung resection, is a risk factor associated with the incidence of Aspergillus pleurisy. Systemic antifungal therapy and adequate pleural irrigation could improve the prognosis. IMPORTANCE: Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), associated with a poor prognosis. The morbidity and mortality of this condition have not been thoroughly studied, and recent research on this topic is limited. The current study included 13 patients diagnosed with Aspergillus pleurisy, with the majority presenting concomitantly with a bronchopleural fistula. Among these patients, nine had a history of thoracic surgery, including lung transplantation and lobectomy. Four patients refused further treatment and were discharged against medical advice, while one patient succumbed to massive hemoptysis 2 years after discharge. This case series provides essential insights into Aspergillus pleurisy and evaluates the therapeutic strategy based on a limited cohort.

Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse.

The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.

MRI-Based Kinetic Heterogeneity Evaluation in the Accurate Access of Axillary Lymph Node Status in Breast Cancer Using a Hybrid CNN-RNN Model.

BACKGROUND: Accurate evaluation of the axillary lymph node (ALN) status is needed for determining the treatment protocol for breast cancer (BC). The value of magnetic resonance imaging (MRI)-based tumor heterogeneity in assessing ALN metastasis in BC is unclear. PURPOSE: To assess the value of deep learning (DL)-derived kinetic heterogeneity parameters based on BC dynamic contrast-enhanced (DCE)-MRI to infer the ALN status. STUDY TYPE: Retrospective. SUBJECTS: 1256/539/153/115 patients in the training cohort, internal validation cohort, and external validation cohorts I and II, respectively. FIELD STRENGTH/SEQUENCE: 1.5 T/3.0 T, non-contrast T1-weighted spin-echo sequence imaging (T1WI), DCE-T1WI, and diffusion-weighted imaging. ASSESSMENT: Clinical pathological and MRI semantic features were obtained by reviewing histopathology and MRI reports. The segmentation of the tumor lesion on the first phase of T1WI DCE-MRI images was applied to other phases after registration. A DL architecture termed convolutional recurrent neural network (ConvRNN) was developed to generate the KHimage (kinetic heterogeneity of DCE-MRI image) score that indicated the ALN status in patients with BC. The model was trained and optimized on training and internal validation cohorts, tested on two external validation cohorts. We compared ConvRNN model with other 10 models and the subgroup analyses of tumor size, magnetic field strength, and molecular subtype were also evaluated. STATISTICAL TESTS: Chi-squared, Fisher's exact, Student's t, Mann-Whitney U tests, and receiver operating characteristics (ROC) analysis were performed. P < 0.05 was considered significant. RESULTS: The ConvRNN model achieved area under the curve (AUC) of 0.802 in the internal validation cohort and 0.785-0.806 in the external validation cohorts. The ConvRNN model could well evaluate the ALN status of the four molecular subtypes (AUC = 0.685-0.868). The patients with larger tumor sizes (>5 cm) were more susceptible to ALN metastasis with KHimage scores of 0.527-0.827. DATA CONCLUSION: A ConvRNN model outperformed traditional models for determining the ALN status in patients with BC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Comprehensive Analysis of TICRR in Hepatocellular Carcinoma Based on Bioinformatics Analysis.

Hepatocellular carcinoma (HCC) is one of the leading cause of cancer-associated death in the world. However, due to the complexity of HCC, it is urgent for us to find a reliable and accurate biomarker for HCC gene therapy.TopBP1-interacting checkpoint and replication regulator (TICRR), known as Treslin in vertebrate and sld3 in yeast, is involved in the tumorigenesis, progression, matastasis, diagnosis, and predicting prognosis of HCC. Disappointingly, the mechanism of TICRR expression in HCC is still not described in detail and requires further analysis. In this study, TCGA ( www.tcga-data.nci.nih.gov/tcga/ ) datasets and GEO ( www.ncbi.nlm.nih.gov/geo ) datasets were used to analyze the expression of TICRR in HCC, the relevance of TICRR mRNA expression and clinicopathological characteristics in patients with HCC, and the relationship between TICRR expression and immune infiltration level in Patients with HCC. Based on MethSurv database, the impact of TICRR in patients with HCC was investigated. In addition, GO/KEGG enrichment analysis of TICRR co-expression was performed using the R package. TICRR was found drastically highly expressed in a variety of cancer types including HCC.ROC curve analysis showed that TICRR had higher accuracy in predicting HCC compared with AFP. The expression level of TICRR was marked positively correlated with tumor stage and prognosis in Patients with HCC.GO/KEGG enrichment analysis showed that TICRR was associated with cell division and cell cycle as well as p53 signaling pathway. In addition, patients with high TICRR methylation of cg05841809, cg09403165, and cg03312532 CpG sites were significantly correlated with poor prognosis of HCC. This study demonstrated that increased TICRR expression in HCC might play an important role in the tumorigenesis, progression, diagnosis, and predicting prognosis of HCC. Therefore, TICRR might be used as a promising diagnostic and prognostic biomarker for HCC gene therapy.

Effects of Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic Review and Meta-analysis.

BACKGROUND: The aim of this study was to summarize the optimal strategy for early feeding in patients with acute pancreatitis. METHODS: The search was undertaken in electronic databases, which compared early with delayed feeding in acute pancreatitis. The primary outcome was the length of hospital stay (LOHS). The second outcomes were intolerance of refeeding, mortality, and total cost of each patient. This meta-analysis followed the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guideline. Research is registered by PROSPERO, CRD42020192133. RESULTS: A total of 20 trials involving 2168 patients were included, randomly assigned to the early feeding group (N = 1033) and delayed feeding group (N = 1135). The LOHS was significantly lower in the early feeding group than the delayed feeding group (mean difference: -2.35, 95% CI: -2.89 to -1.80; P < 0.0001), no matter the mild or severe subgroup ( Pint = 0.69). The secondary outcome of feeding intolerance and mortality were no significant difference (risk ratio: 0.96, 0.40 to 2.16, P = 0.87 and 0.91, 0.57 to 1.46, P = 0.69; respectively). Moreover, the hospitalization cost was significantly less in the early feeding group, resulting in an average savings of 50%. In patients with severe pancreatitis, early feeding after 24 hours may be beneficial ( Pint = 0.001). CONCLUSION: Early oral feeding can significantly reduce the LOHS and hospitalization costs in patients with acute pancreatitis without increasing feeding intolerance or mortality. In patients with severe pancreatitis, early feeding after 24 hours may be beneficial.

Two new bibenzyl methylglucosides as SIRT3 activators obtained through microbial transformation.

Microbial transformation of dihydroresveratrol (DHRSV) using Beauveria bassiana has produced two new methylglucosylated derivatives of DHRSV (1 and 2), whose structures were characterized as 4'-O-(4″-O-methyl-ß-D-glucopyranosyl)-dihydroresveratrol (4'-O-MG DHRSV, 1) and 3-O-(4″-O-methyl-ß-D-glucopyranosyl)-dihydroresveratrol (3-O-MG DHRSV, 2) on the basis of spectroscopic methods. They showed moderate SIRT3 agonistic activity, and compound 2 exhibited the best deacetylation of 406.63% at 10 µM. The activity of 2 increased by 3.12-fold compared with that of DHRSV, since 2 performed better in molecular docking assay (GScore -8.445).

The whole-blood Epstein-Barr virus DNA can serve as a valuable molecular marker for diagnosis and prognosis prediction of nasopharyngeal carcinoma.

The clinical significance and prognostic role of whole-blood EBV-DNA in EBV-associated nasopharyngeal carcinoma (NPC) have not been thoroughly investigated. This study aims to explore the diagnostic and prognostic value of EBV-DNA for NPC in a non-endemic region of China. We enrolled patients with chronic active EBV infection (CAEBV), nasopharyngitis (NA), extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), and NPC. Demographic and clinical data were collected and the diagnostic and prognostic values of EBV-DNA were analyzed. Immunohistochemistry was performed to detect EBV-encoded small ribonucleic acids (EBER), as well as the expression of p53, Ki-67, and epidermal growth factor receptor (EGFR). The levels of pretreatment Epstein-Barr virus DNA (preEBV-DNA) in new NPC cases were found to differ from those in other diseases and exhibited varying age distributions. The threshold value of preEBV-DNA for distinguishing NPC from CAEBV and NA was determined. We confirmed that epistaxis, diabetes mellitus, T3N2 or T4N0-2 stage, and IgM positivity were associated with higher levels of preEBV-DNA, and identified risk factors associated with the prognosis of locoregionally advanced NPC (La-NPC). Patients with intermittently or persistently positive EBV-DNA (IPCP), higher preEBV-DNA levels, and positive Epstein-Barr virus-encoded small RNA (EBER) status (EBERpos) had worse survival. New cases of NPC with elevated levels of EBV in the whole-blood and positive EBER status were shown to have a poor prognosis upon progression to La-NPC. EBV-DNA was found to be an indicator for predicting prognosis in La-NPC and could also be used to distinguish new NPC cases.

Safety, tolerability, and immunogenicity of a CpG/Alum adjuvanted SARS-CoV-2 recombinant protein vaccine (ZR202-CoV) in healthy adults: Preliminary report of a phase 1, randomized, double-blind, placebo-controlled, dose-escalation trial.

This was a phase 1 dose-escalation study of ZR202-CoV, a recombinant protein vaccine candidate containing a pre-fusion format of the spike (S)-protein (S-trimer) combined with the dual-adjuvant system of Alum/CpG. A total of 230 participants were screened and 72 healthy adults aged 18-59 years were enrolled and randomized to receive two doses at a 28-day interval of three different ZR202-CoV formulations or normal saline. We assessed the safety for 28 days after each vaccination and collected blood samples for immunogenicity evaluation. All formulations of ZR202-CoV were well-tolerated, with no observed solicited adverse events ≥ Grade 3 within 7 days after vaccination. No unsolicited adverse events ≥ Grade 3, or serious adverse events related to vaccination occurred as determined by the investigator. After the first dose, detectable immune responses were observed in all subjects. All subjects that received ZR202-CoV seroconverted at 14 days after the second dose by S-binding IgG antibody, pseudovirus and live-virus based neutralizing antibody assays. S-binding response (GMCs: 2708.7 ~ 4050.0 BAU/mL) and neutralizing activity by pseudovirus (GMCs: 363.1 ~ 627.0 IU/mL) and live virus SARS-CoV-2 (GMT: 101.7 ~ 175.0) peaked at 14 days after the second dose of ZR202-CoV. The magnitudes of immune responses compared favorably with COVID-19 vaccines with reported protective efficacy.

Broad and colossal edge supercurrent in Dirac semimetal Cd3As2 Josephson junctions.

Edge supercurrent has attracted great interest recently due to its crucial role in achieving and manipulating topological superconducting states. Proximity-induced superconductivity has been realized in quantum Hall and quantum spin Hall edge states, as well as in higher-order topological hinge states. Non-Hermitian skin effect, the aggregation of non-Bloch eigenstates at open boundaries, promises an abnormal edge channel. Here we report the observation of broad edge supercurrent in Dirac semimetal Cd3As2-based Josephson junctions. The as-grown Cd3As2 nanoplates are electron-doped by intrinsic defects, which enhance the non-Hermitian perturbations. The superconducting quantum interference indicates edge supercurrent with a width of ~1.6 µm and a magnitude of ~1 µA at 10 mK. The wide and large edge supercurrent is inaccessible for a conventional edge system and suggests the presence of non-Hermitian skin effect. A supercurrent nonlocality is also observed. The interplay between band topology and non-Hermiticity is beneficial for exploiting exotic topological matter.

Kinetin inhibits hepatic stellate cell activation and induces apoptosis via interactions with the TGF-ß1/Smad signaling pathway.

Hepatic fibrosis is the pathological repair response of the liver to chronic injury; hepatic stellate cell (HSC) activation is the central link in the pathogenesis of hepatic fibrosis. Previously, we showed that kinetin, a plant cytokinin hormone, has a protective effect on CCl4-induced liver injury in mice. However, the role of kinetin in liver fibrosis remains unclear. We aimed to study these protective effects and to determine the mechanisms by which kinetin mediates HSC activation and apoptosis. For this purpose, the human HSC line LX-2 was treated with 10 ng/ml transforming growth factor-ß1 (TGF-ß1) for 24 h to stimulate activation. We found that treatment with kinetin at the sub-cytotoxic dose of 40 µg/ml for 48 h reduced the expression of the HSC activation marker α-SMA and inhibited the secretion of extracellular matrix proteins. In addition, kinetin was found to inhibit the proliferation and migration of LX-2 cells. We found that kinetin induced apoptosis in LX-2 cells by increasing the level of cleaved-caspase 3 and the Bax-to-Bcl-2 ratio. Interestingly, these effect were not observed in quiescent HSCs, suggesting that they are activation-dependent. Further study showed that kinetin attenuates activation and promotes apoptosis of LX-2 cells in vitro in part by suppressing the TGF-ß1/Smad signaling pathway.

Safety and immunogenicity of a bivalent HPV16/18 vaccine in Chinese females.

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.

Microbial biotransformation to obtain stilbene methylglucoside with GPR119 agonistic activity.

Introduction: Limitation of pharmaceutical application of resveratrol (RSV) and piceatannol (PIC) continue to exist, there is a need to obtain the superior analogs of two stilbenes with promoted activity, stability, and bioavailability. Microbial transformation has been suggested as a common and efficient strategy to solve the above problems. Methods: In this study, Beauveria bassiana was selected to transform RSV and PIC. LC-MS and NMR spectroscopies were used to analyze the transformed products and identify their structures. The biological activities of these metabolites were evaluated in vitro with GPR119 agonist and insulin secretion assays. Single factor tests were employed to optimize the biotransformation condition. Results: Three new methylglucosylated derivatives of PIC (1-3) and two known RSV methylglucosides (4 and 5) were isolated and characterized from the fermentation broth. Among them, 1 not only showed moderate GPR119 agonistic activity with 65.9%, but also promoted insulin secretion level significantly (12.94 ng/mg protein/hour) at 1 µM. After optimization of fermentation conditions, the yield of 1 reached 45.53%, which was increased by 4.2-fold compared with the control. Discussion: Our work presents that 3-O-MG PIC (1), obtained by microbial transformation, is an effective and safer ligand targeting GPR119, which lays a foundation for the anti-diabetic drug design in the future.

Transcriptional adaptor 3 influences the proliferative and invasive phenotypes of non-small cell lung cancer cells via regulating EMT.

Transcriptional adaptor 3 (TADA3/ADA3) is a conserved transcriptional co-activator and is dysregulated in many aggressive tumors. However, the role of TADA3 in non-small cell lung cancer (NSCLC) remains unknown. It was previously demonstrated that TADA3 expression correlates with poor prognosis in patients with NSCLC. In the present study, the expression and function of TADA3 were investigated in cells in vitro and in vivo. TADA3 expression was evaluated in clinical specimens and cell lines using reverse transcription-quantitative PCR and western blot analysis. The TADA3 protein level was significantly higher in human NSCLC specimens compared with matched normal tissues. In human NSCLC cell lines, short hairpin RNA-mediated silencing of TADA3 suppressed their proliferative, migratory and invasive abilities in vitro, and delayed G1 to S phase progression through the cell cycle. Consistent with this, TADA3 silencing increased expression of the epithelial marker E-cadherin and reduced expression of the mesenchymal markers, N-cadherin, Vimentin, Snail, and Slug. To verify the effect of TADA3 on tumor formation and growth in vivo, a mouse tumor xenograft model was established. TADA3 silencing slowed the growth of NSCLC tumor xenografts in nude mice, and excised tumors showed a similarly altered pattern of epithelial-mesenchymal transition (EMT) marker expression. The present results demonstrated the significance of TADA3 in regulating the growth and metastasis of NSCLC and may provide a theoretical basis for early diagnosis and targeted therapy of NSCLC.

Regulation of KDM5C stability and enhancer reprogramming in breast cancer.

Abnormality of enhancer regulation has emerged as one of the critical features for cancer cells. KDM5C is a histone H3K4 demethylase and frequently mutated in several types of cancer. It is critical for H3K4me3 and activity of enhancers, but its regulatory mechanisms remain elusive. Here, we identify TRIM11 as one ubiquitin E3 ligase for KDM5C. TRIM11 interacts with KDM5C, catalyzes K48-linked ubiquitin chain on KDM5C, and promotes KDM5C degradation through proteasome. TRIM11 deficiency in an animal model represses the growth of breast tumor and stabilizes KDM5C. In breast cancer patient tissues, TRIM11 is highly expressed and KDM5C is lower expressed, and their expression is negatively correlated. Mechanistically, TRIM11 regulates the enhancer activity of genes involved in cell migration and immune response by targeting KDM5C. TRIM11 and KDM5C regulate MCAM expression and cell migration through targeting H3K4me3 on MCAM enhancer. Taken together, our study reveals novel mechanisms for enhancer regulation during breast cancer tumorigenesis and development.

Internet Use and Academic Achievement Among Chinese Adolescents: Examining the Mediating Role of Future Orientation in a Rural-Urban Dual System.

Purpose: Given its growing popularity and the richness of its content, the influence of the Internet on the academic achievement of adolescents has attracted increasing attention. However, how Internet use affects adolescents' academic achievement has not yet been fully discussed in the Chinese context. This study sought to examine the relation between Internet use and adolescents' academic achievement, as well as the mediating effect of future orientation and the urban-rural differences in this mediating effect. Materials and Methods: Junior high-school students from three schools in Nanjing, China, were recruited to participate in a correlational survey. A total of 1381 participants aged 12-16 years completed the Internet use questionnaire, the future orientation scale, and reported their scores on the most recent grade unified examination. Results: The analysis results revealed that, after controlling for the variables of grade and gender, (1) the Internet use significantly and positively predicted academic achievement; (2) The future orientation significantly mediated the relation between Internet use and academic achievement; (3) and the effect of Internet use on future orientation was moderated by urban and rural areas. The effect of Internet use in promoting future orientation was only significant among rural adolescents. Conclusion: The results contribute to a better understanding of how Internet use affects adolescents' academic achievement, revealing that Internet use is of particular significance in the development of rural adolescents.

Intraflagellar transport 20 cilia-dependent and cilia-independent signaling pathways in cell development and tissue homeostasis.

Intraflagellar transport (IFT) is an essential condition for ciliogenesis. The primary cilia protrude like antennae and act as chemical or mechanical sensory organelles that coordinate specific receptor localization and signal transduction. IFT20 is the smallest molecule in IFT complex B, which is located in both the cilia and the Golgi complex. Recent studies have shown that IFT20 is a key molecule in multiple signaling pathways. Importantly, in the function of IFT20, signal transduction is not restricted to cilia, but is also involved in non-ciliary functions. Here we summarize current knowledge regarding IFT20-mediated signaling pathways and their relationship with cell development and tissue homeostasis, and analyse the cilia-dependent and cilia-independent mechanisms of IFT20 coordinated signaling pathways and potential crosstalk between the mechanisms. This review provides a comprehensive perspective on IFT20 coordinates signaling mechanisms in cell development and tissue homeostasis.

Imaging-based diagnosis for extraskeletal Ewing sarcoma in pediatrics: A case report.

BACKGROUND: Extraskeletal Ewing sarcoma (EES) is a member of the Ewing sarcoma family of tumors which is pathologically known as a small, round, blue cell tumor involving bone and soft tissue. The prevalence of EES is only 15%-25% of all Ewing sarcoma and EES often occurs in patients aged from 20-mo-old to 30-years-old resulting in an unfavorable prognosis. CASE SUMMARY: The present case report described a 7-year-old patient with a palpable EES mass of 33 mm × 27 mm × 28 mm in the deep neck with symptoms of persistent dyspnea over the past 5 mo. After laboratory examinations, abnormal physiological and biochemical indicators were not found. Ultrasound images presented the mass to be complex, solid and fluid-filled with circumscribed margins and posterior acoustic enhancement. The mass also presented with partial internal vascularity. The contrast-enhanced magnetic resonance imaging scan illustrated the outstanding enhancement with fast perfusion mode in the early arterial phase. CONCLUSION: Our study suggested that a quick-growing mass in the pediatric patient is possibly a malignant tumor whether the mass has well-defined margins or not.