Silencing ribosomal protein L4 enhances the inhibitory effects of triptolide on non-small cell lung cancer cells by disrupting the mouse double minute 2 protein–P53 tumor suppressor pathway

Non-small cell lung cancer(NSCLC)is a malignant tumor with high incidence worldwide.Triptolide(TP),extracted from Tripterygium wilfordii Hook F,exhibits potent broad-spectrum antitumor activity.Although some mechanisms through which TP inhibits NSCLC are well understood,those that involve ribosomal proteins remain yet to be understood.In this study,the transcriptome and proteome were integrated and analyzed.Our data indicated ribosomal protein L4(RPL4)to be a core hub protein in the protein-protein interaction network.RPL4 is overexpressed in NSCLC tissues and cells.Transfection with siRPL4 or TP treatment alone arrested the cell cycle in the G1 phase,induced cell apoptosis,and repressed cell invasion.Compared to treating cells with TP alone or siRPL4,treating them with siRPL4–TP enhanced the inhibition of NSCLC cells.Reduced RPL4 expression reinforced the inhibitory effects of TP on NSCLC cells by disrupting the MDM2-P53 pathway and by altering the expression of PARP1/Snail/cyclin D1.In vivo assays verified that TP induced cell apoptosis and reduced RPL4 expression in xenografts.These findings provide clues to facilitate the development of effective TP-based therapeutic strategies to kill NSCLC cells.

Copper-based nanodots as efficient biomimetic antibiotics for the treatment of oral bacterial infections Author links open overlay panel

Oral infectious diseases caused by a variety of pathogenic bacteria seriously affect the quality of life.However,these diseases remain a clinical challenge because of the lack of simple,safe,and universal prophylactics.To address these limitations,we synthesize CuO_(x)nanodots(CuO_(x)NDs)with excellent Fenton-like reaction activity and utilize them in the treatment of oral bacterial infections.Different from other complicated approaches,CuO_(x)NDs are rationally prepared using a facile one-pot aqueous synthesis.In the presence of H_(2)O_(2),these well-developed CuO_(x)NDs can efficiently catalyze the generation of hydroxyl radicals(·OH)around oral pathogens,leading to the death of various bacteria.Meanwhile,results of biosafety indicate the high biocompatibility and extremely low toxicity of these CuO_(x)NDs.After understanding the admirable in vitro antibacterial effect of CuO_(x)NDs in the presence of H_(2)O_(2),we further explore their in vivo antibacterial performance on several classical animal models including oral mucosal wound model,intragingival bacteria-infected model,and the periodontal infection model.As expected,these CuO_(x)NDs with wide-spectrum antibacterial activity can serve as high-performance antibacterial reagents for the treatment of various oral bacterial infections with the help of H_(2)O_(2).In brief,current nanoplatform can act as efficient antibiotics against oral pathogens with broadening the biomedical applications of copper-based nanomaterials.

超声引导下经支气管针吸活检治疗胸内巨大甲状腺囊肿所致气道狭窄1例

目的探讨超声引导下经支气管针吸活检(EBUS-TBNA)治疗胸内巨大甲状腺囊肿的安全性和有效性,为治疗胸内巨大甲状腺囊肿、尤其是靠近气道的深部甲状腺囊肿提供一项新选择。方法重庆市涪陵中心医院采用EBUS-TBNA治疗胸内巨大甲状腺囊肿所致气道狭窄,术前使用胸部增强CT扫描,术后标本送检,行常规、生化、细菌培养及脱落细胞检查。结果该患者因“咳嗽、气促”入院。胸部平扫CT提示:上纵隔见约60 mm×42 mm的囊性灶,EBUS-TBNA术后患者咳嗽、气促明显改善,复查胸部CT病灶缩小至34 mm×24 mm,气管受压变窄移位较前明显缓解。结论EBUS-TBNA作为一种微创介入治疗方法治疗胸内巨大甲状腺囊肿、尤其是靠近气道的深部甲状腺囊肿是可行的。特别是对于有外科手术禁忌或不愿手术的患者,EBUS-TBNA为其提供了新的选择,但远期疗效和并发症仍需长期随访观察。

Associations between risk factors for cardiovascular diseases and frailty among community-dwelling older adults in Lanzhou,China

Objectives:To examine the relationship between cardiovascular disease risk factors and frailty in a sample of older Chinese adults.Methods:A total of 458 community-dwelling older adults(>65 years)in Lanzhou,Gansu Province of China participated in a cross-sectional survey.Their status was evaluated in terms of frailty phenotype(unintentional weight loss,exhaustion,low activity levels,slowness and weakness).Participants were categorized as not frail,prefrail or frail.Cardiovascular disease risk factors that were assessed included:blood pressure,body mass index,waist circumference,blood glucose,total cholesterol,triglycerides,lowdensity lipoproteins and high-density lipoproteins.Results:Individuals with obesity had an increased risk of prefrailty(OR:2.26;95%CI:1.05,4.84).Hypertension was inversely associated with frailtyamong the participants(OR:0.31;95%CI:0.11,0.87)after adjusting for covariates.Conclusions:The findings suggest that much more attention should be paid to weight control of the elderly in the community for preventing them from transition to prefrailty or frailty.Active prevention and control of cardiovascular diseases among the community-dwelling elder are still of great importance.

Are mindfulness and self-efficacy related to presenteeism among primary medical staff: A cross-sectional study

Objectives: In ensuring public welfare with primary medical and health services,the primary medical staff faces new tasks.Increasing workload,and therefore degrees of stress and burnout,can influence job satisfaction and lead to presenteeism,which is defined as the appearance to be on the job but not actually working.The purpose of this study is to investigate the current worling situation and the relationship between presenteeism and mindfulness of primary medical staff and determine the mediating effect of self-efficacy on this relationship.Method: A cross-sectional survey was performed with 580 primary medical staff from 9 hospitals in Shaanxi province,northwest China.Presenteeism,mindfulness,and self-efficacy were measured by using a general information questionnaire,the Five-Facet Mindfulness Questionnaire,the General Self-Efficacy Scale,and the Stanford Presenteeism Scale.Mediating effect was analyzed by a series of hierarchical multiple regressions.Results: A high level of presenteeism was found among 47.4% of the study participants.Presenteeism was negatively correlated with mindfulness(r--0.409,P < 0.001) and self-efficacy(r--0.678,P < 0.001).A positive correlation was found between mindfulness and self-efficacy(r-0.584,P< 0.001).When controlling for self-efficacy (β =-0.018,P> 0.05),the association was insignificant between presenteeism and mindfulness.Conclusion: The results identified the effect of mindfulness on presenteeism of primary medical staff is realized through self-efficacy,which also suggested to enhance self-efficacy on center location when developing management strategies for mental health education or training among primary medical staff.

Endoscopic submucosal dissection combined with adjuvant chemotherapy for early-stage neuroendocrine carcinoma of the esophagus:A case report

BACKGROUND Neuroendocrine carcinoma(NEC)of the esophagus is rare and highly aggressive,and lacks biological features.Currently,there are no established standard treatments for this cancer.In this report,we describe a patient with large-cell NEC of the esophagus who was successfully treated using endoscopic submucosal dissection(ESD)combined with adjuvant chemotherapy.CASE SUMMARY A 55-year-old woman presented with intermittent mild dysphagia for 2 mo.Gastroscopy revealed a disc-shaped protruding lesion about 18 mm×18 mm in size on the upper esophagus.Endoscopic ultrasonography demonstrated that the bulged lesion originated from the muscularis mucosa.We assessed en bloc resections using ESD for therapeutic diagnosis to devise a safe and appropriate treatment.Histopathological examination revealed a poorly differentiated neoplasm comprising of large cells with marked nuclear atypia and multifocal necrosis.In addition,the specimens had a negative horizontal margin and vertical margins.Depth of invasion was classified as submucosa 2(SM2)without lymphovascular invasion.These histopathological results were consistent with a diagnosis of esophageal NEC,large cell type.Adjuvant therapy has been considered for ESD patients with SM2/SM3 lesions and patients with poorly differentiated lesions.After comprehensive consideration,we initiated combination treatment,i.e.,ESD plus adjuvant chemotherapy.The patient remained disease-free at the 2-year follow-up.CONCLUSION En bloc resection approach using ESD may play a vital role as a diagnostic and therapeutic modality for esophageal NEC.

Preliminary assessment of two non-destructive instrumental techniques for quality evaluation of Lobelia chinensis Lour.

Two non-destructive instrumental methods, infrared spectroscopy （IR） and X-ray diffraction （XRD）, were studied for qualiW evaluation of Lobelia chinensis Lour. （L chinensis）. We obtained the IR spectra and XRD patterns of L chinensis collected from different sources. The similarity of samples was analyzed by cal- culating the cosine coefficient. The cosine values were in the range of 0.83-0.90, indicating that the main components ofL chinensis samples are similar. Sample L1 and L6 showed a slightly lower similarity than that of L2, L3, L4, L5 detected by the two methods, which revealed that IR and XRD methods exhibited analogous detection ability for quality evaluation of L. chinensis. The two methods could be highly re- commended as simple and rapid detection means for quality evaluation of L. chinensis.

Severe Klebsiella pneumoniae pneumonia complicated by acute intra-abdominal multiple arterial thrombosis and bacterial embolism:A case report

BACKGROUND Klebsiella pneumoniae(K.pneumoniae)is a clinically common Gram-negative bacillus that can cause community-and hospital-acquired infections and lead to pneumonia,liver abscesses,bloodstream infections,and other infectious diseases;however,severe pneumonia caused by hypervirulent K.pneumoniae(hv Kp)complicated by acute intra-abdominal multiple arterial thrombosis and bacterial embolism is rarely seen in the clinical setting and has not been reported in the literature.CASE SUMMARY A 51-year-old man was hospitalized with fever and dyspnea.Persistent mild pain in the middle and upper abdomen began at dawn on the 3rd day following admission and developed into persistent severe pain in the left upper abdomen 8h later.Based on chest computed tomography(CT),bronchoscopy,bronchoalveolar lavage fluid metagenomic next-generation sequencing,abdominal aortic CT angiography(CTA),and culture of the superior mesenteric artery embolus,adult community-acquired severe hv Kp pneumonia complicated by acute intraabdominal multiple arterial thrombosis and bacterial embolism was diagnosed.Notably,he recovered and was discharged from the hospital after receiving effective meropenem anti-infection,endovascular contact thrombolytic,and systemic anticoagulant therapies and undergoing percutaneous thrombus aspiration.Ten days later,the patient returned to the hospital for abdominal CTA examination,which indicated blocked initial common pathway of the celiac trunk and superior mesenteric artery,and local stenosis.Therefore,celiac trunk artery stenting was performed in Chongqing Hospital,and postoperative recovery was good.CONCLUSION We report a case of hv Kp severe pneumonia complicated by acute intra-abdominal multiple arterial thrombosis and bacterial embolism and suggest that clinicians should consider the possibility of a Gram-negative bacillus infection and conduct effective pathogen detection in a timely fashion when managing patients with severe community-acquired pneumonia before obtaining bacteriologic and drug sensitivity results.At the same time,when patients have severe pulmonary infection complicated by severe abdominal pain,an acute mesenteric artery embolism should be considered to avoid delays in treatment.

New horizons for therapeutic applications of nanozymes in oral infection

As a category of nanomaterials with excellent catalytic efficiency,great substrate specificity,and highrecovery efficiency,nanozymes have attracted increasing attention in various biomedical applications.Currently,numbers of nanozyme-assisted strategies have been well developed for the theranostics ofvarious diseases by taking advantages of their multienzyme-like characteristics,low cost,and highstability.As the most prevalent oral diseases,oral infection poses a global hazard to human health,andcurrent therapeutic options are insufficient to resolve all the clinical issues.Based on their admirableactivity,nanozymes can be frequently employed in the identification and treatment of various oral infectious disorders.Herein,we provide a brief review focused on the classification of nanozymes,analysesof nanozyme-based antibacterial mechanism,research progress in oral bacterial control,and representative studies of nanozyme-assisted oral inflammatory management.Moreover,major challenges andpotential opportunities regarding the use of nanozymes in oral infectious diseases are also highlightedand discussed.This review not only summarizes the recent studies of nanozymes in oral infection butalso promotes the further development of enzyme-mimetic strategies towards various oral diseases.

Secondary light chain amyloidosis with Waldenstr?m’s macroglobulinemia and intermodal marginal zone lymphoma:A case report

BACKGROUND The co-existence of Waldenstr?m’s macroglobulinemia(WM) with internodal marginal zone lymphoma(INMZL) is rare and often associated with poor prognosis.CASE SUMMARY We present a Chinese female patient who developed secondary light chain amyloidosis due to WM and INMZL and provides opinions on its systemic treatment.A 65-year-old woman was diagnosed with WM 6 years ago and received Bruton tyrosine kinase inhibitor monotherapy for two years.Her INMZL was confirmed due to left cervical lymphadenopathy.The patient presented with oedema in both lower limbs one year ago,and was diagnosed with secondary light chain amyloidosis.Treatment with the BC regimen(rituximab 375 mg/m~2 monthly for 6-8 courses,and bendamustine 90 mg/m~2 per day × 2,monthly for six courses) was initiated,but not tolerated due to toxic side effects.Bortezomibbased therapy was given for two months,including bortezomib,dexamethasone,and zanubrutinb.Oedema in both lower limbs was relieved and treatment efficacy was evaluated as partial remission.CONCLUSION A detailed clinical evaluation and active identification of the aetiology are recommended to avoid missed diagnosis and misdiagnosis.

DNA methylation of SMPD3-based diagnostic biomarkers of NASH and mild fibrosis

Non-alcoholic fatty liver disease(NAFLD)is a liver condition that is widely prevalent across the world.A considerable number of people with NAFLD have the potential to progress to a more severe form of the condition known as nonalcoholic steatohepatitis(NASH),accompanied by bridging fibrosis.This advancement is more likely if the patient has metabolic risk factors such as obesity or type 2 diabetes that deteriorate over time.Additionally,even slight inflammation or fibrosis in NAFLD can significantly increase the likelihood of progression compared to steatosis alone.This underscores the importance of revising the present methods of monitoring NAFLD patients to ensure early detection and effective management of the disease.

Polar Influence of the Organic Modifiers on the Structure of Montmorillonite in Epoxy Nanocomposites

The epoxy nanocomposites with similar amines （CH3（CH2）17NH2 and CH3（CH2）17N（CH3）301） treated montmorillonite clays have been investigated by wide-angle X-ray scattering, transmission electron microscopy （TEM）, differential scanning calorimetry （DSC） and thermal gravimetric analysis （TGA）. Different nanocomposite structures, intercalation and exfoliation were formed by the reaction of octadecyltrimethylammonium chloride-exchanged and octadecylamine-exchanged clays with epoxy resin and phenalkamine as the curing agent, respectively. Results showed that the exfoliated nanocomposite can be obtained when octadecylamine with the lower polarity was used as a modifier. However, the intercalated nanocomposite can be obtained when octadecyltrimethylammonium chloride with higher polarity was used as a modifier.

Single-cell RNA sequencing profiling of the effects of aging on alveolar stem cells

The aging of alveolar stem cells has been linked to many chronic lung diseases, including pulmonary fibrosis. However, the effects of aging on alveolar stem cells during homeostasis and post-injury alveolar repair have not been well characterized. Here we conducted a single-cell RNA sequencing(scRNA-seq) analysis of alveolar stem cells of 3-month-old and 12-month-old mice to characterize the aging effect on alveolar stem cells. Our results have shown that the transcriptomes of alveolar stem cells of 3-month-old and 12-month-old mice are not significantly different under the steady condition. However, after a bleomycin-induced lung injury, the alveolar stem cells of 12-month-old mice show enhanced inflammatory responses and decreased lipid metabolism. Our study suggests a close relationship among aging, lipid metabolism, inflammatory responses and chronic lung diseases.

Identification and characterization of microRNAs in the white-backed planthopper, Sogatella furcifera

MicroRNAs （miRNAs） are a novel class of small, non-coding endogenous RNAs that play critical regulatory roles in many metabolic activities in eukaryotes. Reports of the identification of miRNAs in Sogatella furcifera （white-backed planthopper）, the insect that acts as the only confirmed vector of the southern rice black-streaked dwarf virus （SRBSDV）, are limited. In this study, a total of 382 miRNAs were identified in S. furcifera, including 106 conserved and 276 novel miRNAs, using high-throughput sequencing based on two small RNA libraries from viruliferous and non-viruliferous S. furcifera, and these miRNAs belonged to 52 conserved miRNA families and 58 S. furcifera-specific families, respectively. Comparison with miRNAs from 26 insect species and five other species in miRBase showed that more than half of the conserved miRNA families are highly conserved in Hexapoda, while other miRNAs are only conserved in non- dipterans. Furthermore, 4 117 target genes predicted for the 382 identified miRNAs could be categorized into 45 functional groups annotated by Gene Ontology. Compared with non-viruliferous cells, eight up-regulated miRNAs and four down-regulated miRNAs were identified in cells inoculated with SRBSDV, among which miR-14 and miR-n98a may be involved in the immune response to SRBSDV infection. Analyses of the identified miRNAs will provide insights into the roles of these miRNAs in the regulation and expression of genes involved in the metabolism, development and viral infection of S. furciJbra.

The diversity of adult lung epithelial stem cells and their niche in homeostasis and regeneration

The adult lung,a workhorse for gas exchange,is continually subjected to a barrage of assaults from the inhaled particles and pathogens.Hence,homeostatic maintenance is of paramount importance.Epithelial stem cells interact with their particular niche in the adult lung to orchestrate both natural tissue rejuvenation and robust post-injury regeneration.Advances in single-cell sequencing,lineage tracing,and living tissue imaging have deepened our understanding about stem cell heterogeneities,transition states,and specific cell lineage markers.In this review,we provided an overview of the known stem/progenitor cells and their subpopulations in different regions of the adult lung,and explored the regulatory networks in stem cells and their respective niche which collectively coordinated stem cell quiescence and regeneration states.We finally discussed relationships between dysregulated stem cell function and lung disease.

Adding regular expressions to graph reachability and pattern queries

It is increasingly common to find graphs in which edges are of different types, indicating a variety of relation- ships. For such graphs we propose a class of reachability queries and a class of graph patterns, in which an edge is specified with a regular expression of a certain form, ex- pressing the connectivity of a data graph via edges of var- ious types. In addition, we define graph pattern matching based on a revised notion of graph simulation. On graphs in emerging applications such as social networks, we show that these queries are capable of finding more sensible informa- tion than their traditional counterparts. Better still, their in- creased expressive power does not come with extra complex- ity. Indeed, （1） we investigate their containment and mini- mization problems, and show that these fundamental prob- lems are in quadratic time for reachability queries and are in cubic time for pattern queries. （2） We develop an algorithm for answering reachability queries, in quadratic time as for their traditional counterpart. （3） We provide two cubic-time algorithms for evaluating graph pattern queries, as opposed to the NP-completeness of graph pattern matching via subgraph isomorphism. （4） The effectiveness and efficiency of these al- gorithms are experimentally verified using real-life data and synthetic data.

DEEPEYE: An Automatic Big Data Visualization Framework

Data visualization transforms data into images to aid the understanding of data; therefore, it is an invaluable tool for explaining the significance of data to visually inclined people. Given a(big) dataset, the essential task of visualization is to visualize the data to tell compelling stories by selecting, filtering, and transforming the data, and picking the right visualization type such as bar charts or line charts. Our ultimate goal is to automate this task that currently requires heavy user intervention in the existing visualization systems. An evolutionized system in the field faces the following three main challenges:(1) Visualization verification: to determine whether a visualization for a given dataset is interesting, from the viewpoint of human understanding;(2) Visualization search space: a "boring" dataset may become interesting after an arbitrary combination of operations such as selections,joins, and aggregations, among others;(3) On-time responses: do not deplete the user's patience. In this paper,we present the DEEPEYE system to address these challenges. This system solves the first challenge by training a binary classifier to decide whether a particular visualization is good for a given dataset, and by using a supervised learning to rank model to rank the above good visualizations. It also considers popular visualization operations, such as grouping and binning, which can manipulate the data, and this will determine the search space. Our proposed system tackles the third challenge by incorporating database optimization techniques for sharing computations and pruning.

Preface

Data science targets the data life cycle of real applications,studying phenomena at scales,complexities,and granularities never before possible.This data life cycle encompasses databases and data engineering often lever-aging statistical,machine learning,and arti cial intelligence methods and,in many instances,using massive and heterogeneous collections of potentially noisy datasets.